We found 34 diseases and 169 genes matching your search

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Thymic hypoplasia

Retrieved: 27-07-2015
Source: WIKIPEDIA (Original article)
Associated genes: dgs2, dgcr2, celf2
Thymic hypoplasia is a condition where the thymus is underdeveloped or involuted. Calcium levels can be used to distinguish between the following two conditions associated with thymic hypoplasia: 22q11.2 deletion syndrome: hypocalcemia Ataxia telangiectasia: normal levels of calcium
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Sclerocornea, autosomal dominant

Retrieved: 27-07-2015
Source: OMIM (Original article)

Description

Sclerocornea is a primary anomaly in which scleralization of a peripheral part of the cornea, or the entire corneal tissue, occurs. In the peripheral type, the affected area is vascularized with regular arcades of superficial scleral vessels. In total sclerocornea, the entire cornea is opaque and vascularized (summary by Elliott et al., 1985).

Clinical features

Elliott et al. (1985) reported a 5-generation family in which 9 members had peripheral sclerocornea. All affected members also had autosomal dominant cornea plana (121400), and some had glaucoma, corneal degeneration, posterior embryotoxon, cataract, microphthalmia, nystagmus, esotropia, iris heterochromia, and amblyopia.

Inheritance

Elliott et al. (1985) reported a 5-generation family in which 9 members had peripheral sclerocornea and cornea plana. The pedigree pattern was consistent with autosomal dominant inheritance. They identified 4 reported pedigrees (25 patients) in which peripheral sclerocornea and cornea plana were inherited in an autosomal dominant manner.

From a review of the literature, Elliott et al. (1985) suggested that the autosomal dominant form of sclerocornea is mild, whereas an autosomal recessive form (269400), which is also associated with cornea plana (217300), is severe.

Symptoms

Eyes: Congenital sclerocornea

Inheritance: Autosomal dominant form
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22q11.2 deletion syndrome

Retrieved: 27-07-2015
Source: GARD (Original article)

22q11.2 deletion syndrome

22q11.2 deletion syndrome is a spectrum disorder that includes conditions formerly called DiGeorge syndrome; velocardiofacial syndrome; conotruncal anomaly face syndrome; cases of Opitz G/BBB syndrome; and Cayler cardiofacial syndrome. The features and severity can vary greatly among affected people. Signs and symptoms may include cleft palate, heart defects, recurrent infections, unique facial characteristics, feeding problems, immune system disorders, kidney abnormalities, hypoparathyroidism, thrombocytopenia, scoliosis, hearing loss, developmental delay, and learning disabilities. People with this condition are also more likely to develop certain autoimmune disorders and personality disorders. In most cases, the syndrome occurs for the first time in the affected person; about 10% of cases are inherited from a parent. It is inherited in an autosomal dominant manner
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22q11.2 deletion syndrome

Retrieved: 27-07-2015
Source: GHR (Original article)

What is 22q11.2 deletion syndrome?

22q11.2 deletion syndrome (which is also known by several other names, listed below) is a disorder caused by the deletion of a small piece of chromosome 22. The deletion occurs near the middle of the chromosome at a location designated q11.2. 22q11.2 deletion syndrome has many possible signs and symptoms that can affect almost any part of the body. The features of this syndrome vary widely, even among affected members of the same family. Common signs and symptoms include heart abnormalities that are often present from birth, an opening in the roof of the mouth (a cleft palate), and distinctive facial features. People with 22q11.2 deletion syndrome often experience recurrent infections caused by problems with the immune system, and some develop autoimmune disorders such as rheumatoid arthritis and Graves disease in which the immune system attacks the body's own tissues and organs. Affected individuals may also have breathing problems, kidney abnormalities, low levels of calcium in the blood (which can result in seizures), a decrease in blood platelets (thrombocytopenia), significant feeding difficulties, gastrointestinal problems, and hearing loss. Skeletal differences are possible, including mild short stature and, less frequently, abnormalities of the spinal bones. Many children with 22q11.2 deletion syndrome have developmental delays, including delayed growth and speech development, and learning disabilities. Later in life, they are at an increased risk of developing mental illnesses such as schizophrenia, depression, anxiety, and bipolar disorder. Additionally, affected children are more likely than children without 22q11.2 deletion syndrome to have attention deficit hyperactivity disorder (ADHD) and developmental conditions such as autism spectrum disorders that affect communication and social interaction. Because the signs and symptoms of 22q11.2 deletion syndrome are so varied, different groupings of features were once d...

Keywords

22q11.2 deletion syndrome,Lymphatic Abnormalities,Heart Diseases,Genetic Diseases, Inborn,Congenital Abnormalities,22q11 Deletion Syndrome,Congenital, Hereditary, and Neonatal Diseases and Abnormalities,Musculoskeletal Diseases,Cardiovascular Abnormalities,Endocrine System Diseases,Cardiovascular Diseases,Chromosome Disorders,Craniofacial Abnormalities,Hemic and Lymphatic Diseases,Heart Defects, Congenital,Parathyroid Diseases,Hypoparathyroidism,Abnormalities, Multiple,Musculoskeletal Abnormalities,Lymphatic Diseases,DiGeorge Syndrome,Bones, muscles, and connective tissues,Brain and nervous system,Digestive system,Mouth and teeth,Immune system,Kidneys and urinary system,Heart and circulation,Ear, nose, and throat,velopharyngeal incompetence,COMT,COMT gene,TBX1,TBX1 gene,22q11.2DS,autosomal dominant Opitz G/BBB syndrome,CATCH22,Cayler cardiofacial syndrome,conotruncal anomaly face syndrome (CTAF),deletion 22q11.2 syndrome,DiGeorge syndrome,Sedlackova syndrome,Shprintzen syndrome,VCFS
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Velocardiofacial syndrome

Retrieved: 27-07-2015
Source: OMIM (Original article)

Clinical features

A number sign (#) is used with this entry because the velocardiofacial syndrome and DiGeorge syndrome (DGS; 188400) are caused by a 1.5- to 3.0-Mb hemizygous deletion of chromosome 22q11.2. Haploinsufficiency of the TBX1 gene (602054) in particular is responsible for most of the physical malformations. There is evidence that point mutations in the TBX1 gene can also cause the disorder.The del22q11 syndrome is associated with a highly variable phenotype despite the uniformity of the chromosomal deletion that causes the syndrome in most patients.

Shprintzen et al. (1981) reported on 39 patients with a syndrome characterized by the following frequent features: cleft palate, cardiac anomalies, typical facies, and learning disabilities. Less frequent features included microcephaly, mental retardation, short stature, slender hands and digits, minor auricular anomalies, and inguinal hernia. The Pierre Robin syndrome was present in 4. The heart malformation was most often ventricular septal defect. In the group studied, mother and daughter were affected in 2 instances, mother and son in 1, and mother and both daughter and son in 1.

Fitch (1983) found small optic discs with tortuous vessels in an affected 6-year-ol...

Symptoms

INHERITANCE: Autosomal dominant

GROWTH: [Height]; Short stature

HEAD AND NECK: [Head]; Microcephaly; [Face]; Long; Pierre Robin syndrome; Retrognathia; [Eyes]; Narrow palpebral fissures; Small optic discs; Tortuous retinal vessels; Posterior embryotoxon; [Ears]; Minor auricular anomalies; [Nose]; Square nasal root; Decreased nasopharyngeal lymphoid tissue; Prominent tubular nose; Hypoplastic nasal alae; Bulbous nasal tip; [Mouth]; Cleft palate; Velopharyngeal insufficiency; Small open mouth; Pharyngeal hypotonia

CARDIOVASCULAR: [Heart]; Congenital abnormality in 85%; Ventricular septal defect; Tetralogy of Fallot; [Vascular]; Right aortic arch; Aberrant left subclavian; Internal carotid artery abnormalities

RESPIRATORY: [Lung]; Primary pulmonary dysgenesis, unilateral (reported in 2 unrelated patients)

ABDOMEN: [External features]; Inguinal hernia; Umbilical hernia

SKELETAL: [Hands]; Slender hands and digits

NEUROLOGIC: [Central nervous system]; Learning disability; Mental retardation; [Behavioral/psychiatric manifestations]; Blunt or inappropriate affect; Psychotic illness; Paranoia; Autistic features; Aggression; Mood swings

VOICE: Nasal voice

ENDOCRINE FEATURES: Neonatal hypocalcemia, rare

IMMUNOLOGY: Frequent infections T-lymphocyte dysfunction, rare

LABORATORY ABNORMALITIES: Monosomy for 22q11

MISCELLANEOUS: Overlapping features of DiGeorge syndrome; Incidence is estimated to be between 1 in 2,000 to 1 in 7,000 live births

MOLECULAR BASIS: A contiguous gene syndrome caused by deletion (1.5Mb - 3.0Mb) of 22q11.2
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Sclerocornea

Retrieved: 27-07-2015
Source: WIKIPEDIA (Original article)
Associated genes: rax, prkra, lbx1
Sclerocornea is a congenital anomaly of the eye in which the cornea blends with sclera, having no clear-cut boundary. The extent of the resulting opacity varies from peripheral to total (sclerocornea totalis). The severe form is thought to be inherited in an autosomal recessive manner, but there may be another, milder form that is expressed in a dominant fashion. In some cases the patients also have abnormalities beyond the eye (systemic), such as limb deformities and craniofacial and genitourinary defects. According to one tissue analysis performed after corneal transplantation, the sulfation pattern of keratan sulfate proteoglycans in the affected area is typical for corneal rather than scleral tissue. Sclerocornea may be concurrent with cornea plana.

External links

Congenital Clouding of the Cornea - eMedicine; by Noah S Scheinfeld, MD, JD, FAAD and Benjamin D Freilich, MD, FACS
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Episodic ataxia type 4

Retrieved: 27-07-2015
Source: Orphanet (Original article)

Episodic ataxia type 4 (EA4) is a very rare form of Hereditary episodic ataxia (see this term) characterized by late-onset episodic ataxia, recurrent attacks of vertigo, and diplopia. Last update: January 2014
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Episodic ataxia, type 4

Retrieved: 27-07-2015
Source: OMIM (Original article)

Clinical features

For a phenotypic description and a discussion of genetic heterogeneity of episodic ataxia, see EA1 (160120).In 16 members of a white, rural North Carolina family, Farmer and Mustian (1963) described recurrent attacks of vertigo, diplopia, and ataxia beginning in early adulthood. Slowly progressive cerebellar ataxia occurred in some. Vance et al. (1984) identified a second extensively affected kindred which, like the family of Farmer and Mustian (1963), lived in North Carolina. Although no relationship between the 2 kindreds could be established, such was suspected. Small et al. (1996) examined ocular motility in these families.

Damji et al. (1996) isolated DNA from 19 affected individuals from the 2 multigenerational North Carolina families originally described by Farmer and Mustian (1963) and Vance et al. (1984) who had periodic vestibulocerebellar ataxia in an autosomal dominant pedigree pattern. The disorder was characterized by defective smooth pursuit, gaze-evoked nystagmus, ataxia, and vertigo. The age of onset ranged from the third to the sixth decade.

Mapping

In the families originally described by Farmer and Mustian (1963) and Vance et al. (1984), Damji et al. (1996) excluded linkage to loci linked to EA1 and EA2 (108500), as well as to spinocerebellar ataxia types 1 (164400), 2 (183090), 3 (109150), 4 (600223), and 5 (600224).

Nomenclature

Damji et al. (1996) symbolized the disorder PATX for periodic ataxia.

Although Steckley et al. (2001) referred to PATX as episodic ataxia-3 (EA3) and the disorder in 606554 as EA4, the same group (Cader et al., 2005) later referred to the disorder described by Steckley et al. (2001) in 606554 as EA3. We have thus chosen to designate PATX as episodic ataxia-4 (EA4).

Symptoms

INHERITANCE: Autosomal dominant

HEAD AND NECK: [Ears]; Tinnitus; [Eyes]; Diplopia; Oscillopsia; Abnormal smooth pursuits; Inability to suppress vestibuloocular reflex (VOR); Gaze-evoked nystagmus; Esophoria

ABDOMEN: [Gastrointestinal]; Nausea

NEUROLOGIC: [Central nervous system]; Ataxia, episodic; Vertigo; Spasticity

MISCELLANEOUS: Age of onset 30 to 60 years; Symptoms precipitated by sudden movement, stress, exertion, fatigue' Attacks typically last for hours; Attacks are not responsive to acetazolamide
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Corneal opacification with other ocular anomalies

Retrieved: 27-07-2015
Source: OMIM (Original article)
Associated genes: pxdn

Description

A number sign (#) is used with this entry because of evidence that corneal opacification associated with other ocular anomalies, such as cataract, microcornea, microphthalmia, and anterior segment dysgenesis, is caused by homozygous or compound heterozygous mutation in the PXDN gene (605158) on chromosome 2p25.In sclerocornea there is congenital, nonprogressive corneal opacification that may be peripheral, sectoral, or central in location. Visual prognosis is related to the central corneal involvement. The cornea has a flat curvature. The majority of cases are bilateral (summary by Smith and Traboulsi, 2012).

Isolated sclerocornea is caused by displacement of the limbal arcades and may be associated with cornea plana; in this condition, the anterior chamber is visible and the eye is not microphthalmic. In complex sclerocornea, however, corneal opacification is associated with microphthalmia, cataract, and/or infantile glaucoma. The central cornea is usually relatively clear, but the thickness is normal or increased, never reduced (summary by Nischal, 2007).

Clinical features

Khan et al. (2011) studied a consanguineous Pakistani family (family MEP60) segregating autosomal recessive cataract, microcornea, and corneal opacity, which the authors designated CCMCO. The 3 affected family members exhibited corneas that were 7 to 8 mm in diameter, and anterior segment examination showed that the peripherally located corneal opacity appeared to be due to the sclera encroaching on the cornea. Peripheral iridocorneal adhesion was also present. Vision was reduced to counting fingers in all 3 patients. The family history suggested that the changes were not progressive.

Khan et al. (2011) reported a large consanguineous Pakistani family (family MEP59) in which 4 sibs and 2 cousins had corneal opacification as well as cataract and microcornea. The lens was of normal size and shape, and the fundus was normal by indirect ophthalmoscopy. Khan et al. (2011) also described a consanguineous Cambodian family (family CA2) with 4 affected sibs who had severe corneal opacification, 3 of whom also had bilateral buphthalmos and exhibited severe vascularization of the cornea. Elevated intraocular pressures were present in 3 of the sibs, including the patient without buphthalmos. The extent of corneal opacification prevented visualization of the anterior chamber or fundus, and the presence or absence of cataract could not be deter...

Symptoms

INHERITANCE: Autosomal recessive

HEAD AND NECK: [Eyes]; Corneal opacification, partial or total; Sclerocornea (in some patients); Cataract (in some patients); Microcornea (in some patients); Iridocorneal dysgenesis (in some patients); Increased intraocular pressure (in some patients); Buphthalmos (in some patients); Microphthalmia (in some patients); Anterior segment dysgenesis (in some patients)

MOLECULAR BASIS: Caused by mutation in the homolog of Drosophila peroxidasin gene (PXDN, 605158.0001)
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22q11.2 deletion syndrome

Retrieved: 27-07-2015
Source: Orphanet (Original article)
Associated genes: pi4ka

22q11.2 deletion syndrome (DS) is a chromosomal anomaly which causes a congenital malformation disorder whose common features include cardiac defects, palatal anomalies, facial dysmorphism, developmental delay and immune deficiency. The worldwide incidence is estimated at 1/2,000-1/4,000 live births. 22q11.2 DS shows a variable clinical phenotype that can range from mild to severe. Congenital heart defects (77% of cases) include mainly conotruncal malformations such as truncus arteriosus, tetralogy of Fallot and vetricular septal defect. More than 75% of patients present with palatal anomalies (e.g. overt cleft palate, cleft lip and palate, velopharyngeal incompetence) that may lead to hypernasal speech, feeding and swallowing difficulties. Developmental delay is frequent. Many patients present with mild facial dysmorphism (e.g. malar flatness, ptosis, hypertelorism, epicanthal folds, prominent nasal root) and vertebral anomalies (e.g. butterfly vertebrae, hemivertebrae). 75% of patients have an immune deficiency due to thymic aplasia/hypoplasia that renders them susceptible to various infections. Patients also have a higher risk of developing an autoimmune disease such as idiopathic thrombocytopenic purpura and juvenile idiopathic arthritis (see these terms). Neonatal hypocalcemia is observed in 50% of cases. It usually resolves but can reappear at any age or after an infection, surgery or pregnancy. Additional clinical findings may include gastrointestinal anomalies (intestinal malrotation, imperforate anus), hearing loss, renal anomalies (renal agenesis), dental anomalies (enamel hypoplasia), learning problems and/or psychiatric disorders (attention deficit hyperactivity disorder, schizophrenia). The broad spectrum of clinical phenotypes that the syndrome encompasses was previously divided into distinct syndromes (e.g. DiGeorge syndrome, velocardiofacial syndrome, cardiofacial syndrome) but are now known to be etiologically identical and are referred to ...
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Congenital primary aphakia

Retrieved: 27-07-2015
Source: Orphanet (Original article)
Associated genes: foxe3

Congenital primary aphakia (CPA) is characterised by an absence of the lens. The prevalence is unknown. CPA can be associated with variable secondary ocular defects (including aplasia/dysplasia of the anterior segment of the eye, microphthalmia, and in some cases absence of the iris, retinal dysplasia, or sclerocornea). CPA results from early developmental arrest, around the 4th-5th week of embryogenesis, which prevents the formation of any lens structure. Mutations in the FOXE3 gene were identified in three affected siblings born to consanguineous parents. Last update: December 2006
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Congenital primary aphakia

Retrieved: 27-07-2015
Source: GARD (Original article)
Associated genes: foxe3

Congenital primary aphakia

Congenital primary aphakia (CPA) is a rare eye condition that is present at birth in which the lens is missing. In some cases, CPA can be associated with other eye abnormalities including microphthalmia, absence of the iris, anterior segment aplasia, and/or sclerocornea (when the cornea blends with the sclera). This condition is thought to result from an abnormality during the 4th or 5th week of fetal development, which prevents the formation of any lens structure in the eye. Mutations in the FOXE3 gene have been associated with this condition. CPA is thought to be inherited in an autosomal recessive fashion. Click here to view a diagram of the eye
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Aphakia, congenital primary

Retrieved: 27-07-2015
Source: OMIM (Original article)
Associated genes: foxe3

Clinical features

A number sign (#) is used with this entry because of evidence that congenital primary aphakia can be caused by homozygous mutation in the FOXE3 gene (601094) on chromosome 1p33.

Heterozygous mutations in FOXE3 have been identified with anterior segment dysgenesis with cataract (107250).Congenital primary aphakia (CPA) is a rare developmental disorder characterized by absence of the lens, the development of which is normally induced during the fourth to fifth week of human embryogenesis. This original failure leads, in turn, to complete aplasia of the anterior segment of the eye, which is the diagnostic histologic criterion for CPA. In contrast, in secondary aphakic eyes lens induction occurs and the lens vesicle develops to some degree but is progressively resorbed perinatally, leading to less severe ocular defects. Valleix et al. (2006) analyzed a consanguineous family in which 3 sibs had bilateral aphakia, microphthalmia, and complete agenesis of the ocular anterior segment. Two sibs exhibited sclerocornea, and 1 had megacornea.

Molecular genetics

To identify the genetic cause of the congenital primary aphakia in the 3 sibs described by them, Valleix et al. (2006) sequenced 7 candidate genes chosen on the basis of either animal models or spatial and temporal patterns of expression. They identified homozygosity for a null mutation in the FOXE3 gene (C240X; 601094.0002). The findings indicated a possible critical role for FOXE3 very early in the lens developmental program, perhaps earlier than any role recognized elsewhere for this gene.

Symptoms

INHERITANCE: Autosomal recessive

HEAD AND NECK: [Eyes]; Congenital primary aphakia; Microphthalmia; Anterior segment of eye aplasia; Absent iris; Sclerocornea

MISCELLANEOUS: Allelic to anterior segment mesenchymal dysgenesis (107250)

MOLECULAR BASIS: Caused by mutation in the forkhead box E3 gene (FOXE3, 601094.0002)
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Rodrigues blindness

Retrieved: 27-07-2015
Source: OMIM (Original article)

Description

On the island of Rodrigues in the Indian Ocean, Wallis and Beighton (1992) identified a brother and sister with moderately severe mental retardation, blindness due to severe ocular malformations (microphthalmia, microcornea, and sclerocornea), short stature, dysmorphic facial features (narrow nasal bridge with distal flaring of the nose and prominent ears), fine and sparse hair, and malaligned teeth. Wallis and Beighton (1992) emphasized, possibly inappropriately, the hair and dental changes in entitling their report.

Symptoms

Neuro: Mental retardation

Eyes: Blindness; Microphthalmos; Microcornea; Sclerocornea

Growth: Short stature

Facies: Dysmorphic facial features; Narrow nasal bridge; Distal nasal flaring; Prominent ears

Hair: Fine hair; Sparse hair

Teeth: Malaligned teeth

Inheritance: Autosomal recessive
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Ectodermal dysplasia - blindness

Retrieved: 27-07-2015
Source: Orphanet (Original article)

This syndrome is characterized by intellectual deficit, blindness caused by ocular malformations (microphthalmia, microcornea and sclerocornea), short stature, dysmorphic facial features (narrow nasal bridge and prominent ears), hypotrichosis, and malaligned teeth. It has been described in two siblings (brother and sister) and is likely to be transmitted as an autosomal recessive trait. Last update: October 2006
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Cognitive impairment with or without cerebellar ataxia

Retrieved: 27-07-2015
Source: OMIM (Original article)
Associated genes: scn8a

Clinical features

A number sign (#) is used with this entry because of evidence that cognitive impairment with or without cerebellar ataxia is caused by heterozygous mutation in the SCN8A gene (600702) on chromosome 12q13. One such family has been reported.Trudeau et al. (2006) reported a family of Swedish and Norwegian origin with highly variable neurologic deficits. The proband was a 9-year-old boy with markedly delayed psychomotor development, attention deficit disorder, and cerebellar ataxia. Features included ataxic wide-based gait, dysmetria in the upper limbs, and dysarthria, with normal strength, tone, and reflexes. He also had esophoria, amblyopia, and gaze-evoked nystagmus. Brain MRI showed moderate pancerebellar atrophy, accentuated in the vermal and parasagittal regions, as well as optic nerve hypoplasia. There were no cerebral abnormalities. His mother and maternal aunt had a history of emotional instability and mild cognitive impairment, and a first cousin had attention deficit-hyperactivity disorder (ADHD; 143465). A brother of the proband was noted to have impaired cognition and another cousin was noted to have ADHD, but they were not studied at the molecular level. In addition, none of the family members besides the proband was available for formal clinical evaluation or brain imaging studies. The proband was ascertained during a study of 151 patients with ataxia who were screened specifically for mutations in the SCN8A gene (see MOLECULAR GENETICS).

Molecular genetics

Because SCN8A is widely expressed in neurons of the central and peripheral nervous systems, and because mutations in the mouse ortholog result in ataxia and other movement disorders, Trudeau et al. (2006) screened the 26 coding exons of SCN8A in 151 patients with inherited or sporadic ataxia and no mutations in known ataxia-related genes. They found a heterozygous 2-bp deletion in exon 24 (600702.0001) in a 9-year-old boy with mental retardation, pancerebellar atrophy, and ataxia. Three additional family members who were heterozygous for this mutation exhibited milder cognitive behavioral deficits including ADHD. However, Trudeau e...

Symptoms

INHERITANCE: Autosomal dominant

HEAD AND NECK: [Eyes]; Optic nerve hypoplasia (1 patient); Gaze-evoked nystagmus (1 patient); Esophoria (1 patient); Amblyopia (1 patient)

NEUROLOGIC: [Central nervous system]; Cognitive impairment (3 patients); Mental retardation (1 patient); Ataxia (1 patient); Dysmetria (1 patient); Dysarthria (1 patient); Brain MRI shows cerebellar atrophy (1 patient); [Behavioral/psychiatric manifestations]; Attention deficit-hyperactivity disorder (3 patients); Emotional lability (2 patients)

MISCELLANEOUS: Three patients in one family have been reported (as of October 2011), and only one mutation carrier exhibited mental retardation and ataxia

MOLECULAR BASIS: Caused by mutation in the voltage-gated sodium channel, type VIII, alpha subunit gene (SCN8A, 600702.0001)
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DiGeorge syndrome

Retrieved: 27-07-2015
Source: WIKIPEDIA (Original article)
DiGeorge syndrome 22q11.2 deletion syndrome, which has several presentations including DiGeorge syndrome (DGS), DiGeorge anomaly, velo-cardio-facial syndrome, Shprintzen syndrome, conotruncal anomaly face syndrome, Strong syndrome, congenital thymic aplasia, and thymic hypoplasia, is a syndrome caused by the deletion of a small piece of chromosome 22. The deletion occurs near the middle of the chromosome at a location designated 22q11.2—signifying its location on the long arm of one of the pair of chromosomes 22, on region 1, band 1, sub-band 2. It has a prevalence estimated at 1:4000. The syndrome was described in 1968 by the pediatric endocrinologist Angelo DiGeorge.DiGeorge AM. Congenital absence of the thymus and its immunologic consequences: concurrence with congenital hypoparathyroidism. IV(1). White Plains, NY: March of Dimes-Birth Defects Foundation; 1968:116-21 22q11 deletion is also associated with truncus arteriosus (see TOF).

Presentation

The features of this syndrome vary widely, even among members of the same family, and affect many parts of the body. Characteristic signs and symptoms may include birth defects such as congenital heart disease, defects in the palate, most commonly related to neuromuscular problems with closure (velo-pharyngeal insufficiency), learning disabilities, mild differences in facial features, and recurrent infections. Infections are common in children due to problems with the immune system's T-cell mediated response that in some patients is due to an absent or hypoplastic thymus. 22q11.2 deletion syndrome may be first spotted when an affected newborn has heart defects or convulsions from hypocalcemia due to malfunctioning parathyroid glands and low levels of parathyroid hormone (parathormone). Affected individuals may also have any other kind of birth defect including kidney abnormalities and significant feeding difficulties as babies. Disorders such as hypothyroidism and hypoparathyroidism or thrombocytopenia (low platelet levels), and psychiatric illnesses are common late-occurring features. Microdeletions in chromosomal region 22q11.2 are associated with a 20 to 30-fold increased risk of schizophrenia. Studies provide various rates of 22q11.2 deletion syndrome in schizophrenia, ranging from 0.5 to 2% and averaging about 1%, compared with the overall estimated 0.025% risk of the 22q11.2 deletion syndrome in the general population. Salient features can be summarized using the mnemonic CATCH-22 to describe DiGeorge syndrome, with the 22 to remind one the chromosomal abnormality is found on the 22 chromosome, as below: Cardiac Abnormality (especially tetralogy of Fallot)Abnormal facies Thymic aplasia Cleft palate Hypocalcemia/Hypoparathyroidism.

Nomenclature

The signs and symptoms of 22q11 deletion syndrome are so varied that different groupings of its features were once regarded as separate conditions. These original classifications included velo-cardio-facial syndrome, Shprintzen syndrome, DiGeorge sequence/syndrome, Sedlackova...
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Digeorge syndrome

Retrieved: 27-07-2015
Source: OMIM (Original article)
Digeorge syndrome

Description

A number sign (#) is used with this entry because DiGeorge syndrome is caused by a 1.5- to 3.0-Mb hemizygous deletion of chromosome 22q11.2. Haploinsufficiency of the TBX1 gene (602054) in particular is responsible for most of the physical malformations. There is evidence that point mutations in the TBX1 gene can also cause the disorder.DiGeorge syndrome (DGS) comprises hypocalcemia arising from parathyroid hypoplasia, thymic hypoplasia, and outflow tract defects of the heart. Disturbance of cervical neural crest migration into the derivatives of the pharyngeal arches and pouches can account for the phenotype. Most cases result from a deletion of chromosome 22q11.2 (the DiGeorge syndrome chromosome region, or DGCR). Several genes are lost including the putative transcription factor TUPLE1 which is expressed in the appropriate distribution. This deletion may present with a variety of phenotypes: Shprintzen, or velocardiofacial, syndrome (VCFS; 192430); conotruncal an...

Symptoms

INHERITANCE: Autosomal dominant

GROWTH: [Height]; Short stature (20% of adults); [Weight]; Obesity (35% of adults)

HEAD AND NECK: [Face]; Micrognathia; [Ears]; Low-set ears; Abnormal folded pinna; Middle ear abnormalities; Hearing deficits (28% of adults); [Eyes]; Posterior embryotoxon; Tortuous retinal vasculature; Hypertelorism; Short palpebral fissures; Eyelid hooding; Amblyopia; Strabismus (15% of adults); Exotropia; Esophoria; Sclerocornea; Accommodative esotropia; Complicated strabismus; [Nose]; Blunted nose; Short philtrum; [Mouth]; High arched palate; Cleft palate; Bifid uvula

CARDIOVASCULAR: [Heart]; Cardiovascular malformations (26% of adults); Tetralogy of Fallot; Truncus arteriosus; Interrupted aortic arch; Right aortic arch; Ventricular septal defect; [Vascular]; Patent ductus arteriosus

ABDOMEN: [External features]; Umbilical hernia; Femoral hernia; [Biliary tract]; Cholelithiasis (19% of adults)

GENITOURINARY: [External genitalia, male]; Inguinal hernia; [Kidney]; Unilateral renal agenesis; Renal dysplasia; Hydronephrosis

SKELETAL: [Spine]; Scoliosis (47% of adults)

SKIN, NAILS, HAIR: [Skin]; Severe acne (23% of adults); Seborrhea (35% of adults)

NEUROLOGIC: [Central nervous system]; Mild to moderate learning difficulties; Delayed psychomotor development; Late-onset speech development; Tetany; Seizures (40%); [Behavioral/psychiatric manifestations]; Attention deficit disorder; Schizophrenia (22% of adults); Bipolar disorder

VOICE: Hypernasal speech

ENDOCRINE FEATURES: Parathyroid hypoplasia; Parathyroid absence; Thymic hypoplasia; Thymic aplasia; Accessory thyroid tissue; Hypothyroidism (20% of adults)

IMMUNOLOGY: Immune defect due to a T cell defic...
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22q11.2 Deletion Syndrome

Retrieved: 28-07-2015
Source: GeneReviews (Original article)
22q11.2 Deletion Syndrome

Summary

Summary Clinical characteristics

Individuals with 22q11.2 deletion syndrome (22q11.2DS) have a range of findings including the following: Congenital heart disease (74% of individuals), particularly conotruncal malformations (tetralogy of Fallot, interrupted aortic arch, ventricular septal defect, and truncus arteriosus) Palatal abnormalities (69%), particularly velopharyngeal incompetence, submucosal cleft palate, bifid uvula, and cleft palate Characteristic facial features (present in the majority of individuals of northern European heritage) Learning difficulties (70%-90%) An immune deficiency (regardless of the clinical presentation) (77%) Additional findings include the following: Hypocalcemia (50%) Significant feeding and swallowing problems; constipation with or without structural gastrointestinal anomalies (intestinal malrotation, imperforate anus, and Hirschsprung disease) Renal anomalies (31%) Hearing loss (both conductive and sensorineural) Laryngotrac...

Diagnosis

Diagnosis Clinical Diagnosis 22q11

2 deletion syndrome (22q11.2DS) is suspected in individuals with a range of findings including: Congenital heart disease (particularly conotruncal defects) Palatal abnormalities (especially velopharyngeal insufficiency [VPI]) Hypocalcemia Immune deficiency Learning difficulties (especially a non-verbal learning disability, with a greater than ten-point split between the verbal intelligence quotient [VIQ] and the performance intelligence quotient [PIQ]: VIQ>PIQ) Characteristic facial features Less frequently seen functional differences include: Severe dysphagia Growth hormone deficiency Autoimmune disease (thrombocytopenia, juvenile rheumatoid arthritis, Grave’s disease, vitiligo, neutropenia, hemolytic anemia) Hearing loss (sensorineural and conductive) Psychiatric illness Autism Other important structural anomalies contributing to diagnosis: Skeletal findings: pre- and postaxial polydactyly of the hands, postaxial polydactyly of the feet, supernumerary ribs, hemivertebrae, and craniosynostosis (coronal, lambdoidal) Genitourinary tract anomalies: renal agenesis, hydronephrosis, multicystic/dysplastic kidneys, duplicated kidney, horseshoe kidney, absent uterus, hypospadias, inguinal hernia, and cryptorchidism Laryngotracheoesophageal abnormalities: vascular ring, laryngeal web, laryngotracheal malacia, and subglottic stenosis Ophthalmologic findings: tortuous retinal vessels, ptosis, posterior embryotoxon, sclerocornea, coloboma, cataract, anophthalmia, and strabismus CNS abnormalities: cerebellar atrophy, polymicrogyria, enlarged sylvian fissures, neural tube defects, tethered cord, unprovoked seizures, and asymmetric crying facies Gastrointestinal anomalies: anteriorly placed/imperforate anus, esophageal atresia, jejunal atresia, accessory spleens, umbilical hernia, diaphragmatic hernia, intestinal malrotation, and Hirschsprung disease Preauricular tags and/or pits Neoplasms: Hepatoblastoma, renal cell...
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Microphthalmia, isolated 3

Retrieved: 27-07-2015
Source: OMIM (Original article)
Associated genes: rax

Nomenclature

A number sign (#) is used with this entry because of evidence that isolated microphthalmia-3 (MCOP3) is caused by compound heterozygous mutation in the RAX gene (601881) on chromosome 18q21.

For a phenotypic description and a discussion of genetic heterogeneity of isolated microphthalmia, see MCOP1 (251600).The term 'anophthalmia' has been misused in the medical literature. True or primary anophthalmia is incompatible with life; in such cases, the primary optic vesicle has stopped developing and the abnormal development involves major defects in the brain as well (Francois, 1961). The diagnosis can only be made histologically (Reddy et al., 2003; Morini et al., 2005; Smartt et al., 2005), but this is rarely done. In most published cases, the term 'anophthalmia' is used as a synonym for the more appropriate terms 'extreme microphthalmia' or 'clinical anophthalmia.'

Clinical features

Voronina et al. (2004) reported a 12-year-old boy, born to nonconsanguineous parents, who had right clinical anophthalmia and ankyloblepharon and left microphthalmia with sclerocornea. Ocular ultrasound showed a very small cystic remnant on the right and persistent fetal vasculature and total retinal detachment on the left. An EEG at 7 years of age showed abnormal slowing of background activity consistent with underlying cortical activity, and the patient was diagnosed as autistic. MRI of the brain was normal.

Molecular genetics

Voronina et al. (2004) analyzed the RAX gene in 75 individuals with clinical anophthalmia and/or microphthalmia and identified compound heterozygosity for a nonsense mutation (601881.0001) and a missense mutation (601881.0002) in a 12-year-old boy with right clinical anophthalmia and left microphthalmia who also had a diagnosis of autism.

In a 2-year-old Algerian girl with bilateral clinical anophthalmia, the third child born to nonconsanguineous parents, Lequeux et al. (2008) identified compound heterozygosity for a deletion and a nonsense mutation in the RAX gene (601881.0003 and 601881.0004, respectively). The girl had no other dysmorphic features or malformations and normal psychomotor development. MRI of the brain showed bilateral absence of eyes with fibrous tissue in the orbits and hypoplastic optic nerves and chiasma; the hypothalamus and pituitary gland were normal.

Symptoms

INHERITANCE: Autosomal recessive

HEAD AND NECK: [Eyes]; Anophthalmia, clinical; Microphthalmia; Ankyloblepharon; Sclerocornea

MOLECULAR BASIS: Caused by mutation in the retina and anterior neural fold homeobox gene (RAX, 601881.0001)

Microphthalmia–dermal aplasia–sclerocornea syndrome

Retrieved: 27-07-2015
Source: WIKIPEDIA (Original article)
Microphthalmia–dermal aplasia–sclerocornea syndrome (also known as "MIDAS syndrome") is a condition characterized by linear skin lesions. It can be associated with HCCS.

See also

List of cutaneous conditions

External links

GeneReview/NIH/UW entry on Microphthalmia with Linear Skin Defects Syndrome

Microphthalmia with linear skin defects syndrome

Retrieved: 27-07-2015
Source: Orphanet (Original article)

MIDAS syndrome (Microphthalmia, Dermal Aplasia, and Sclerocornea), also called microphthalmia with linear skin defects syndrome, is characterized by ocular defects (microphthalmia, orbital cysts, corneal opacities) and linear skin dysplasia of the neck, head, and chin. It has been reported in less than 50 patients. Additional findings may include agenesis of corpus callosum, sclerocornea, chorioretinal abnormalities, hydrocephalus, seizures, intellectual deficit, and nail dystrophy. It is transmitted as an X-linked dominant trait with male lethality. Last update: September 2006

Linear skin defects with multiple congenital anomalies 1

Retrieved: 27-07-2015
Source: OMIM (Original article)

Description

A number sign (#) is used with this entry because of evidence that linear skin defects with multiple congenital anomalies, also known as microphthalmia with linear skin defects (MLS) and MIDAS syndrome, is caused by mutation in the HCCS gene (300056) on chromosome Xp22.The microphthalmia with linear skin defects syndrome (MLS) is an X-linked dominant disorder characterized by unilateral or bilateral microphthalmia and linear skin defects--which are limited to the face and neck, consisting of areas of aplastic skin that heal with age to form hyperpigmented areas--in affected females and in utero lethality for males (Wimplinger et al., 2006).

- Genetic Heterogeneity of Linear Skin Defects with Multiple Congenital Anomalies

Also see LSDMCA2 (300887), caused by mutation in the COX7B gene (300885) on Xq21, and LSDMCA3 (300952), caused by mutation in the NDUFB11 gene (300403) on Xp11.3.

Clinical features

In 2 females with de novo X;Y translocations, Al Gazali et al. (1990) described manifestations including irregular linear areas of erythematous skin hypoplasia involving the head and neck, along with eye findings that included microphthalmia, corneal opacities, and orbital cysts. The features were considered distinct from those of either focal dermal hypoplasia (FDH; 305600) or incontinentia pigmenti (308300). Cytogenetic analysis showed that the breakpoint in the X chromosome was at Xp22.3 in both females. Al Gazali et al. (1990) suggested that deletion or disruption of DNA sequences in the region of Xp22.3 was responsible for this syndrome. It had been suggested that focal dermal hypoplasia maps to the same region, Xp22.31. T...

Symptoms

INHERITANCE: X-linked dominant

GROWTH: [Height]; Short stature (3rd-10th percentile)

HEAD AND NECK: [Head]; Microcephaly; [Ears]; Hearing loss; [Eyes]; Microphthalmia; Sclerocornea; Cataracts; Iris coloboma; Pigmentary retinopathy

CARDIOVASCULAR: [Heart]; Atrial septal defect; Ventricular septal defect; Cardiac conduction defects; Oncocytic cardiomyopathy; [Vascular]; Overriding aorta

CHEST: [Diaphragm]; Diaphragmatic hernia

ABDOMEN: [Gastrointestinal]; Anteriorly placed anus; Imperforate anus

GENITOURINARY: [External genitalia, male]; Small penis; Hypospadias; Chordee; [External genitalia, female]; Hypertrophic clitoris; [Internal genitalia, female]; Hypoplastic uterus; Ovotestis

SKIN, NAILS, HAIR: [Skin]; Asymmetric, linear skin defects (anterior face and neck)

NEUROLOGIC: [Central nervous system]; Agenesis of corpus callosum; Absence of septum pellucidum; Hydrocephalus; Mild to severe mental retardation (24%); Infantile seizures; Colpocephaly

LABORATORY ABNORMALITIES: Distal Xp22.3 segmental monosomy

MISCELLANEOUS: The acronym MIDAS is MIcrophthalmia, Dermal Aplasia, Sclerocornea

MOLECULAR BASIS: Caused by mutation in the holocytochrome C synthase gene (HCCS, 300056.0001)

Microphthalmia with linear skin defects syndrome

Retrieved: 27-07-2015
Source: GHR (Original article)

What is microphthalmia with linear skin defects syndrome?

Microphthalmia with linear skin defects syndrome is a disorder that mainly affects females. In people with this condition, one or both eyes may be very small or poorly developed (microphthalmia). Affected individuals also typically have unusual linear skin markings on the head and neck. These markings follow the paths along which cells migrate as the skin develops before birth (lines of Blaschko). The skin defects generally improve over time and leave variable degrees of scarring. The signs and symptoms of microphthalmia with linear skin defects syndrome vary widely, even among affected individuals within the same family. In addition to the characteristic eye problems and skin markings, this condition can cause abnormalities in the brain, heart, and genitourinary system. A hole in the muscle that separates the abdomen from the chest cavity (the diaphragm), which is called a diaphragmatic hernia, may occur in people with this disorder. Affected individuals may also have short stature and fingernails and toenails that do not grow normally (nail dystrophy).

How common is microphthalmia with linear skin defects syndrome?

The prevalence of microphthalmia with linear skin defects syndrome is unknown. More than 50 affected individuals have been identified.

What are the genetic changes related to microphthalmia with linear skin defects syndrome?

Mutations in the HCCS gene or a deletion of genetic material that includes the HCCS gene cause microphthalmia with linear skin defects syndrome. The HCCS gene carries instructions for producing an enzyme called holocytochrome c-type synthase. This enzyme is active in many tissues of the body and is found in the mitochondria, the energy-producing centers within cells. Within the mitochondria, the holocytochrome c-type synthase enzyme helps produce a molecule called cytochrome c. Cytochrome c is involved in a process called oxidative phosphorylation, by which mitochondria generate adenosine triphosphate (ATP), the cell's main energy source. It also plays a role in the self-destructio...

Keywords

microphthalmia with linear skin defects syndrome,Microphthalmos,Congenital Abnormalities,Eye Abnormalities,Congenital, Hereditary, and Neonatal Diseases and Abnormalities,Eye Diseases,Skin, hair, and nails,Eyes and vision,HCCS,HCCS gene,MCOPS7,microphthalmia dermal aplasia and sclerocornea,microphthalmia syndromic 7,microphthalmia syndromic 7,microphthalmia with linear skin lesions syndrome,MIDAS syndrome,MLS syndrome,syndromic microphthalmia-7,National Library of Medicine,NLM,National Institutes of Health,NIH,health problem,health problems,disease,diseases,human genetics,gene,genes,genetic disease,genetic conditions,genetic disorders,medical genetics,genetics education,genetics glossary,gene reference,genetics reference,human genetic health,genomic medicine,molecular medicine,genetic testing,genomic medicine,gene therapy,pharmacogenomics,genetic counseling,counseling,gene testing,genome,hereditary family history,future of medicine,Disease and Gene Association,congenital,heritable disorders
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Facial paresis, hereditary congenital, 3

Retrieved: 27-07-2015
Source: OMIM (Original article)
Associated genes: hoxb1

Clinical features

A number sign (#) is used with this entry because of evidence that hereditary congenital facial paresis-3 (HCFP3) is caused by homozygous mutation in the HOXB1 gene (142968) on chromosome 17q21.

For a phenotypic description and a discussion of genetic heterogeneity of hereditary congenital facial paresis (HCPF), see 601471.Webb et al. (2012) studied 2 brothers, born of consanguineous parents of conservative German American background, who had previously been diagnosed with Moebius syndrome (157900). The sibs were noted to have bilateral facial weakness, sensorineural hearing loss, and esotropia in the first months of life, and developed feeding difficulties and speech delays requiring oromotor and speech therapies. Both underwent surgery to correct esotropia, and both wore glasses for high hyperopia. MRI in the older brother at 8 months of age revealed bilateral absence of the facial nerve and bilateral abnormal tapering of the basal turn of the cochlea. Auditory brainstem response testing in both boys revealed bilateral mild to moderate high frequency hearing loss with normal absolute latencies of waveforms, and distortion product otoacoustic emissions were absent in both children, supporting abnormal cochlear function. Stapedius reflexes were intact bilaterally. Examination at 7.25 years and 2.9 years of age, respectively, revealed midface retrusion, low-set and posteriorly rotated ears, upturned nasal tip, and smooth philtrum in both boys. Neither child showed any facial movement. Taste discrimination, salivation, and lacrimation were intact, as was general sensation over the concha of the ear and skin behind the auricle. Webb et al. (2012) noted that because both boys had partially accommodative esotropia with high hyperopia and full eye movements, they did not meet the criteria for Moebius syndrome. Their parents and a brother were unaffected, and there was no family history of strabismus or facial weakness.

Mapping

In 2 brothers with congenital facial paresis and their unaffected consanguineous conservative German American parents, Webb et al. (2012) performed linkage and homozygosity mapping and identified a single approximate...

Symptoms

INHERITANCE: Autosomal recessive

HEAD AND NECK: [Face]; Facial paresis, congenital bilateral; Facial muscle weakness of muscles innervated by CN VII; Midface retrusion (in some patients); Micrognathia (in some patients); Smooth philtrum (in some patients); [Ears]; Hearing loss, sensorineural, mild to moderate; Low-set ears (in some patients); Posteriorly rotated ears (in some patients); [Eyes]; Esotropia (in some patients); Esophoria (in some patients); [Nose]; Upturned nasal tip (in some patients)

NEUROLOGIC: [Central nervous system]; Facial paresis, congenital bilateral; Facial muscle weakness of muscles innervated by CN VII

MISCELLANEOUS: Nonprogressive disorder

MOLECULAR BASIS: Caused by mutation in the homeobox B1 gene (HOXB1, 142968.0001)
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Cataract-microcornea syndrome

Retrieved: 27-07-2015
Source: Orphanet (Original article)
Associated genes: gja8, crybb1

Cataract-microcornea syndrome is characterized by the association of congenital cataract and microcornea without any other systemic anomaly or dysmorphism. To date, more than 15 families showing microcornea-cataract syndrome have been described. Clinical findings include a corneal diameter inferior to 10 mm in both meridians in an otherwise normal eye, and an inherited cataract, which is most often bilateral posterior polar with opacification in the lens periphery. The cataract progresses to form a total cataract after visual maturity has been achieved, requiring cataract extraction in the first to third decade of life. Microcornea-cataract syndrome can be associated with other rare ocular manifestations, including myopia, iris coloboma, sclerocornea and Peters anomaly (see this term). Transmission is in most cases autosomal dominant, but cases of autosomal recessive transmission have recently been described. There is marked genetic heterogeneity. Mutations have been described in several crystallin genes (CRYAA, CRYBB1, CRYGD), and in the gap junction protein alpha 8 gene (GJA8). Ophthalmologic and general examination allows other syndromes to be excluded. Cataract surgery has to be performed in order to restore visual acuity and avoid amblyopia. Visual acuity after uncomplicated cataract extraction is relatively good. Expert reviewer(s) Dr Alrun LEROUX-GRONEMEYER Pr Gottfried NAUMANN Last update: October 2007
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Microphthalmia, isolated 1

Retrieved: 27-07-2015
Source: OMIM (Original article)
Associated genes: cyp11b2, mcop1, prss56

Description

One form of isolated microphthalmia (MCOP1) has been mapped to chromosome 14q32.Microphthalmia designates a heterogeneous group of ocular malformations with a more or less evident reduction in the size of the eyeball. Additional features include high hypermetropia and a short axial length. The size of the anterior chamber and the cornea may also be reduced, whereas the lens is normal or thicker than usual for age (summary by Fuchs et al., 2005).

- Genetic Heterogeneity of Isolated Microphthalmia

MCOP2 (610093) is caused by mutation in the CHX10 gene (142993) on chromosome 14q24. MCOP3 (611038) is caused by mutation in the RAX gene (601881) on chromosome 18q21.3. MCOP4 (613094) is caused by mutation in the GDF6 gene (601147) on chromosome 8q22.1. MCOP5 (611040) is caused by mutation in the MFRP gene (606227) on chromosome 11q23. MCOP6 (613517) is caused by mutation in the PRSS56 gene (613858) on chromosome 2q37.1. MCOP7 (613704) is caused by mutation in the GDF3 gene (606522) on chromosome 12p13.1. MCOP8 (615113) is caused by mutation in the ALDH1A3 gene (600463) on chromosome 15q26.

Nomenclature

The term 'anophthalmia' has been misused in the medical literature. True or primary anophthalmia is incompatible with life; in such cases, the primary optic vesicle has stopped developing and the abnormal development involves major defects in the brain as well (Francois, 1961). The diagnosis can only be made histologically (Reddy et al., 2003; Morini et al., 2005; Smartt et al., 2005), but this is rarely done. In most published cases, the term 'anophthalmia' is used as a synonym for the more appropriate terms 'extreme microphthalmia' or 'clinical anophthalmia.'

Clinical features

Cecchetto (1920) reported a pedigree in which 2 brothers, each married to a first cousin, had a child with bilateral clinical anophthalmia. The common grandparents were also first cousins. Hesselberg (1951) reported affected children from first-cousin parents. Sorsby (1934) discovered early reports of affected sibs with normal parents. Ashley (1947) reported an affected Japanese brother and sister.

Warburg (1993) gave a comprehensive phenotypic and etiologic classification of microphthalmos and ocular coloboma. She included the description of a consanguineous Arab family showing that the phenotype in autosomal recessive microphthalmos may include congenital cystic eye, anophthalmos, microphthalmos, or coloboma. Some affected family members were mentally retarded, while others were mentally healthy.

Gill and Harris (1959) reported a family in which the proband and her great-aunt had microphthalmos. Wolff (1930) described a family of 10 children whose parents were first cousins and among whom 3 males and 2 females had microphthalmos, high-grade hyperopia (up to +20d), and glaucoma. Holst (1952) observed 6 cases in 2 rela...

Symptoms

HEENT: Microphthalmos; Anophthalmos; Nanophthalmos; High-grade hyperopia; Glaucoma

Inheritance: Autosomal recessive; also dominant forms
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Brittle cornea syndrome 2

Retrieved: 27-07-2015
Source: OMIM (Original article)
Associated genes: prdm5

Clinical features

A number sign (#) is used with this entry because of evidence that brittle cornea syndrome-2 (BCS2) is caused by homozygous mutation in the PRDM5 gene (614161) on chromosome 4q27.

For a general phenotypic description and discussion of genetic heterogeneity of brittle cornea syndrome, see BCS1 (229200).Cameron (1993) described 11 patients with blue sclerae, limbus-to-limbus corneal thinning, hypermobile joints, and consanguineous parents. Corneal rupture occurred in 7 patients (9 eyes) either spontaneously or following minimal trauma. Acute hydrops occurred in 3 patients. Bilateral microcornea was present in 1 patient, and 2 patients had unilateral increased corneal diameter due to secondary glaucoma after trauma. Peripheral sclerocornea was present bilaterally in 5 patients. Curvature abnormalities included cornea plana, keratoconus, and keratoglobus. Systemic abnormalities included increased skin laxity, pectus excavatum, scoliosis, congenital hip dislocation, recurrent shoulder dislocation, high-frequency hearing loss, high-arched palate, and mitral valve prolapse. Cameron (1993) stated that the term 'blue sclera' in this syndrome is a misnomer, as the sclera is more transparent and thinner than normal, revealing underlying uveal tissue; the blue appearance is most apparent in the region of the ciliary body, giving the appearance of a 'halo' at the limbus. In addition, photographic comparisons in patients followed for more than 5 years showed a less prominent blue appearance of the sclera with increasing age.

Burkitt Wright et al. (2011) reported a large consanguineous Pakistani family (designated 'BC-001') in which 4 sisters had corneal rupture after minor trauma. The affected sisters had high myopia, blue sclerae, keratoconus, keratoglobus, soft skin with easy bruising, hypermobility of the small joints, femoral epiph...

Symptoms

INHERITANCE: Autosomal recessive

HEAD AND NECK: [Ears]; Hearing loss, sensorineural and conductive; Hypercompliant tympanic membranes; [Eyes]; Blue sclerae; Corneal thinning; Corneal rupture; Myopia; Keratoconus; Keratoglobus; Megalocornea (in some patients); Sclerocornea (in some patients); Cornea plana (in some patients)

ABDOMEN: [External features]; Hernia, inguinal, umbilical, or epigastric (in some patients)

SKELETAL: Small joint hypermobility; Abnormal gait (in some patients); Increased fractures (in some patients); [Pelvis]; Developmental dysplasia of the hip (in some patients)

SKIN, NAILS, HAIR: [Skin]; Soft with easy bruising (in some patients); Poor healing with abnormal scarring (in some patients); Hyperelasticity (in some patients)

MUSCLE, SOFT TISSUE: Myalgia (in some patients)

MISCELLANEOUS: Heterozygous carriers have blue sclerae, small joint hypermobility, and mild thinning of cornea

MOLECULAR BASIS: Caused by mutation in the PR-domain containing protein-5 gene (PRDM5, 614161.0001)
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Mietens syndrome

Retrieved: 27-07-2015
Source: Orphanet (Original article)

Mietens syndrome is a very rare syndrome consisting of corneal opacity, nystagmus, strabismus, flexion contracture of the elbows with dislocation of the head of the radius and abnormally short ulnae and radii. To date, only nine cases have been reported. Ocular findings are striking. Dysmorphic features are not characteristic except for a small pinched nose and a depressed nasal root. Intellectual deficit and growth delay are observed in the majority of patients. An autosomal recessive pattern of inheritance is probable. Last update: July 2010
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Mental retardation syndrome, mietens-weber type

Retrieved: 27-07-2015
Source: OMIM (Original article)

Description

Mietens and Weber (1966) reported a family in which 4 of 6 offspring of unaffected, second-cousin parents had a syndrome consisting of mental retardation, corneal opacity, nystagmus, strabismus, small pinched nose, flexion contracture of the elbows, dislocation of head of radius, abnormally short ulna and radius, and clinodactyly.

Martinez-Glez et al. (2006) described 9-year-old female twins with Mietens-Weber syndrome. The patients were born after a normal pregnancy to young and nonconsanguineous parents. Findings noted soon after birth included horizontal nystagmus and dislocation of both elbows because of abnormally short radii and ulnae in both twins. Further clinical examinations showed moderate psychomotor delay with marked language compromise. Karyotypes were normal in both girls. Martinez-Glez et al. (2006) reviewed the literature and concluded that only 9 cases, including their 2, had been reported. The inheritance pattern appeared to be autosomal recessive. Martinez-Glez et al. (2006) stated that the finding of congenital nystagmus and radii dislocation in a patient with mental retardation is highly suggestive of the disorder.

Symptoms

INHERITANCE: Autosomal recessive

GROWTH: [Other]; Marked growth retardation (-3 S.D.)

HEAD AND NECK: [Eyes]; Microsclerocornea; Strabismus; Nystagmus; [Nose]; Narrow, pointed nose

SKELETAL: [Limbs]; Short forearms; Elbow flexion contractures; Shortened radii and ulnae; Dislocated radial head; Absent proximal radial epiphyses; [Feet]; Pes planus valgus

MUSCLE, SOFT TISSUE: Atrophic calf muscles

NEUROLOGIC: [Central nervous system]; Mental retardation, mild, some patients (IQ 70-80)
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Oculoauricular syndrome

Retrieved: 27-07-2015
Source: OMIM (Original article)
Associated genes: hmx1

Clinical features

A number sign (#) is used with this entry because of evidence that oculoauricular syndrome (OCACS) is caused by homozygous mutation in the HMX1 gene (142992) on chromosome 4p16.Franceschetti and Valerio (1945) described a 3-year-old Swiss girl who had bilateral mild microphthalmia with marked corneal opacities similar to corneal sclerosis and increased intraocular pressure on the left, and whose vision was limited to perception of light. She also had bilateral symmetric abnormalities of the external ear, characterized by a primitive appearing intertragic notch and coloboma of the lobule. Her 6-year-old brother also had eye and ear malformations, including bilateral mild microphthalmia with microcornea, inferonasal coloboma of the iris, anteroinferior polar cataract, and microphakia. The fundus was not visible, and he could recognize objects at 30 cm. His ear findings were identical to his sister's; both sibs had normal hearing. Their mother had a bilateral mild symmetric abnormality of the ear lobes. The authors stated that there were no other anomalies in the patients or other family members.

Schorderet et al. (2008) reported a developmental defect affecting the eye and external ear in 3 members of a consanguineous Swiss family, 2 of whom had been described by Franceschetti and Valerio (1945). Their proband, the great-nephew of the previously described sibs, presented at 2 months of age with congenital nystagmus, bilateral microcornea, posterior synechiae, bilateral cataract, colobomatous microphthalmia of the right eye, and anterior segment dysgenesis consisting of incomplete coloboma of the iris, stromal iris cyst of the right eye, and iridocorneal adherences in the left eye. Fundal examination revealed dysplastic macropapillae reminiscent of morning glory syndrome (see 120430), macular hypoplasia, and peripheral inferonasal chorioretinal coloboma. The cataract was rapidly progressive, requiring surgery at 11 months of age. Ophthalmoscopy at 7 years of age revealed the presence of circumferential abnormalities of the retinal pigment epithelium and chorioretinal atrophic lacunae at the equator, and the patient had rod-cone dystrophy on electroretinogram (ERG). His ears showed lobular aplasia, a narrow intertragic notch, and an abnormal bridge connecting the crus of the helix and antihelix, resulting in complete separation between the cymba and the conqua. Audiogram and...

Symptoms

INHERITANCE: Autosomal recessive

HEAD AND NECK: [Ears]; Lobular aplasia; Narrow intertragic notch; Abnormal bridge connecting the crus of the helix and antihelix; [Eyes]; Nystagmus; Microphthalmia; Microcornea; Cataract; Coloboma; Chorioretinal atrophic lacunae; Morning glory-like dysplastic macropapillae; Macular hypoplasia; Microphakia; Rod-cone dystrophy; Sclerocornea; Increased intraocular pressure

MOLECULAR BASIS: Caused by mutation in the homeobox (H6 family) 1 gene (HMX1, 142992.0001)

Microphthalmia/Anophthalmia/Coloboma Spectrum

Retrieved: 28-07-2015
Source: GeneReviews (Original article)

Summary

Summary Clinical characteristics

Microphthalmia, anophthalmia, and coloboma comprise the MAC spectrum of ocular malformations. Microphthalmia refers to a globe with a total axial length that is at least two standard deviations below the mean for age. Anophthalmia refers to complete absence of the globe in the presence of ocular adnexa (eyelids, conjunctiva, and lacrimal apparatus). Coloboma refers to the ocular malformations that result from failure of closure of the optic fissure. Chorioretinal coloboma refers to coloboma of the retina and choroid. Iris coloboma causes the iris to appear keyhole-shaped. Microphthalmia, anophthalmia, and coloboma may be unilateral or bilateral; when bilateral they may occur in any combination. Diagnosis/testing. Molecular genetic testing (which can include sequence analysis, gene-targeted deletion/duplication analysis, and chromosome microarray analysis [CMA]) can identify a genetic cause in 80% of individuals with bilateral anophthalmia/severe microphthalmia and in up to 20% of all individuals with an ocular malformation in the MAC spectrum. Management. Treatment of MAC spectrum: Prosthetic intervention is appropriate for those with severe microphthalmia and anophthalmia. In many infants, an ocularist can start shortly after birth to expand the palpebral fissures, conjunctival cul-de-sac, and orbit using conformers of progressively increasing size. An oculoplastic surgeon can help determine the most suitable options for surgical intervention after age six months (when postnatal growth of the orbit can be assessed) and before the age that orbital dimensions are fixed (after which extensive orbital reconstruction may be required). Children with reduced vision may benefit from visual aids and other visual resources as well as early intervention to help optimize psychomotor development, educational endeavors, life skills, and mobility. Protection of the healthy eye in those with unilateral involvement is recommended. Genetic counseling. When an inherited or de novo chromosome abnormality or a specific syndrome is identified either by phenotypic findings or by genetic/genomic testing, genetic counseling is indicated based on the mode of inheritance for that condition.

Clinical characteristics

Microphthalmia, anophthalmia, and coloboma comprise the MAC spectrum of ocular malformations. Microphthalmia refers to a globe with a total axial length that is at least two standard deviations below the mean for age. Anophthalmia refers to complete absence of the globe in the presence of ocular adnexa (eyelids, conjunctiva, and lacrimal apparatus). Coloboma refers to the ocular malformations that result from failure of closure of the optic fissure. Chorioretinal coloboma refers to coloboma of the retina and choroid. Iris coloboma causes the iris to appear keyhole-shaped. Microphthalmia, anophthalmia, and coloboma may be unilateral or bilateral; when bilateral they may occur in any combination.Micr...
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8q21.11 microdeletion syndrome

Retrieved: 27-07-2015
Source: Orphanet (Original article)
Associated genes: cyp11b2

8q21.11 microdeletion syndrome encompasses heterozygous overlapping microdeletions on chromosome 8q21.11 resulting in intellectual disability, facial dysmorphism comprising a round face, ptosis, short philtrum, Cupid's bow and prominent low-set ears, nasal speech and mild finger and toe anomalies. The prevalence is unknown but 8q21.11 microdeletion syndrome is rare. To date, 13 cases, of which 5 from the same family, have been clinically and molecularly characterized without a notable gender discrepancy. Very frequent facial anomalies in patients with 8q21.11 microdeletions include a round face with full cheeks, ptosis, short philtrum, small mouth with downturned corners and a Cupid's bow of the upper lip, low-set and prominent ears and nasal speech. Mild to moderate intellectual disability is present in all affected individuals. Mild finger and toe anomalies such as camptodactyly, syndactyly of the 3rd and 4th fingers, and broadening of the first rays are relatively common. Most also suffer from hypotonia. Other features comprise a high forehead, short palpebral fissures, wide nasal bridge, underdeveloped alae, micrognathia, short neck, hearing loss and ophthalmic manifestations including strabismus, sclerocornea and microphthalmia. The syndrome is caused by a heterozygous deletion at chromosome region 8q21.11, reported in the majority of patients. The constant microdeletion overlap region contains the ZFHX4 gene, a microRNA gene of unknown function, as well as a pseudogene and in 7 cases heterozygous deletions of PEX2 were noted. Microdeletions appear de novo or are inherited from affected parents in an autosomal dominant manner. Diagnosis is based on clinical manifestations leading to cytogenetic analysis. The 8q21.11 microdeletion can be detected using a range of molecular techniques including array based comparative genomic hybridization (array CGH) and fluorescence in situ hybridization (FISH). Differential diagnosis includes Schilbach-Rott syndrome, ...
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Corneal dystrophy - perceptive deafness

Retrieved: 27-07-2015
Source: Orphanet (Original article)
Associated genes: slc4a11, ched1, cdk13

Corneal dystrophy-perceptive deafness (CDPD) or Harboyan syndrome is a degenerative corneal disorder characterized by the association of congenital hereditary endothelial dystrophy (CHED; see this term) with progressive, postlingual sensorineural hearing loss. To date, 24 cases from 11 families of various origins (Asian Indian, South American Indian, Sephardi Jewish, Brazilian Portuguese, Dutch, Gypsy, Moroccan and Dominican) have been reported. The ocular manifestations in CDPD include diffuse bilateral corneal edema occurring with severe corneal clouding, blurred vision, visual loss and nystagmus. They are apparent at birth or within the neonatal period and are indistinguishable from the ocular findings characterizing autosomal recessive CHED (CHED2). Hearing deficit in CDPD is slowly progressive and is typically identified in patients between 10 and 25 years of age. There are no reported cases with prelingual deafness, however, significant hearing loss in children as young as 4 years old has been detected by audiometry, suggesting that hearing may be affected early in the disease course, even at birth. CDPD is caused by mutations in the SLC4A11 gene located at the CHED2 locus on chromosome 20p13-p12, indicating that CHED2 and CDPD are allelic disorders. A total of 62 different SLC4A11 mutations have been reported in 98 families (92 with CHED2 and six with CDPD). More than 50% of the reported CDPD cases have been associated with parental consanguinity and all reported cases have been consistent with autosomal recessive transmission. Diagnosis is based on clinical criteria, detailed ophthalmological assessment and audiometry. Molecular confirmation of the clinical diagnosis is feasible. A variety of genetic, metabolic, developmental and acquired diseases presenting with clouding of the cornea should be considered in the differential diagnosis (Peters anomaly, sclerocornea, limbal dermoids and congenital glaucoma; see these terms). Audiometry must be perfor...
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Microphthalmia with brain and digit anomalies

Retrieved: 27-07-2015
Source: Orphanet (Original article)
Associated genes: bmp4

This syndrome is characterised by anophthalmia or microphthalmia, retinal dystrophy, and/or myopia, associated in some cases with cerebral anomalies. It has been described in two families. Polydactyly may also be present. Linkage analysis allowed identification of mutations in the BMP4 gene, which has already been shown to play a role in eye development. Last update: May 2008
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Anophthalmia/microphthalmia - esophageal atresia

Retrieved: 27-07-2015
Source: Orphanet (Original article)
Associated genes: sox2, otx2

Anophthalmia-esophageal atresia syndrome belongs to the group of syndromic microphthalmias and is characterized by the association of uni- or bilateral anophthalmia or microphthalmia, and esophageal atresia with or without trachoesophageal fistula. Prevalence is unknown but less than 30 cases (male and female) have been described in the literature so far. Genital anomalies (hypospadias, micropenis, and/or cryptorchidism) were reported in most of the male patients. Several other associated anomalies have been described including developmental anomalies of the central nervous system, cardiac defects, vertebral anomalies, growth failure, sensorineural hearing loss, anterior pituitary hypoplasia and hypogonadotropic hypogonadism. Intellectual development was normal in some cases, but mild to significant psychomotor delay has also been reported. Inheritance is autosomal dominant and the syndrome is caused by heterozygous mutations or deletions in the SOX2 gene (3q26.3-q27). Last update: February 2010
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SOX2 anophthalmia syndrome

Retrieved: 27-07-2015
Source: GHR (Original article)
Associated genes: sox2, otx2

What is SOX2 anophthalmia syndrome?

SOX2 anophthalmia syndrome is a rare disorder characterized by abnormal development of the eyes and other parts of the body. People with SOX2 anophthalmia syndrome are usually born without eyeballs (anophthalmia), although some individuals have small eyes (microphthalmia). The term anophthalmia is often used interchangeably with severe microphthalmia because individuals with no visible eyeballs typically have some remaining eye tissue. These eye problems can cause significant vision loss. While both eyes are usually affected in SOX2 anophthalmia syndrome, one eye may be more affected than the other. Individuals with SOX2 anophthalmia syndrome may also have seizures, brain abnormalities, slow growth, delayed development of motor skills (such as walking), and mild to severe learning disabilities. Some people with this condition are born with a blocked esophagus (esophageal atresia), which is often accompanied by an abnormal connection between the esophagus and the trachea (tracheoesophageal fistula). Genital abnormalities have been described in affected individuals, especially males. Male genital abnormalities include undescended testes (cryptorchidism) and an unusually small penis (micropenis).

How common is SOX2 anophthalmia syndrome?

SOX2 anophthalmia syndrome is estimated to affect 1 in 250,000 individuals. About 10 percent to 15 percent of people with anophthalmia in both eyes have SOX2 anophthalmia syndrome.

What genes are related to SOX2 anophthalmia syndrome?

Mutations in the SOX2 gene cause SOX2 anophthalmia syndrome. This gene provides instructions for making a protein that plays a critical role in the formation of many different tissues and organs during embryonic development. The SOX2 protein regulates the activity of other genes, especially those that are important for normal development of the eyes. Mutations in the SOX2 gene prevent the production of functional SOX2 protein. The absence of this protein disrupts the activity of genes that are essential for the development of the eyes and other pa...

Keywords

SOX2 anophthalmia syndrome,Anophthalmos,Congenital Abnormalities,Eye Abnormalities,Congenital, Hereditary, and Neonatal Diseases and Abnormalities,Eye Diseases,Eyes and vision,SOX2,SOX2 gene,AEG syndrome,Anophthalmia-esophageal-genital syndrome,SOX2-related eye disorders,syndromic microphthalmia 3,National Library of Medicine,NLM,National Institutes of Health,NIH,health problem,health problems,disease,diseases,human genetics,gene,genes,genetic disease,genetic conditions,genetic disorders,medical genetics,genetics education,genetics glossary,gene reference,genetics reference,human genetic health,genomic medicine,molecular medicine,genetic testing,genomic medicine,gene therapy,pharmacogenomics,genetic counseling,counseling,gene testing,genome,hereditary family history,future of medicine,Disease and Gene Association,congenital,heritable disorders,inherited disorders,heritable diseases,inherited diseases,family disorders,family diseases,inborn disorders,inborn diseases,birth defects
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Dermoids of cornea

Retrieved: 27-07-2015
Source: OMIM (Original article)
Associated genes: cyp11b2, cnd

Clinical features

Henkind et al. (1973) described 2 male cousins of Puerto Rican extraction who were born with bilateral opaque corneas with no other ocular or systemic abnormality. Their mothers were sisters. The unaffected sister of one of the affected males (Henkind's III-3) gave birth to an affected male (Nitowsky, 1978). Histopathologic study showed that opacifications were due to corneal dermoids, i.e., abnormal mesoblastic tissue covered by epithelium. The authors reviewed other forms of neonatal corneal opacities. Congenital hereditary corneal dystrophy (217700) and sclerocornea (269400) are most likely to be confused with corneal dermoid. Ring dermoid of the cornea (180550) is presumably a distinct entity. The condition described by Guizar-Vazquez et al. (1981) may have been autosomal recessive and, therefore, distinct. Because corneal dermoids represent tissue elements not normally found in the cornea, they are considered to be chistomas.

Dar et al. (2001) provided follow-up on the pedigree originally described by Henkind et al. (1973). They ascertained 23 members of the family, including 6 affected males. There was no evidence of male-to-male transmission. In all cases the dermoids appeared as bilateral superficial grayish layers with irregular raised whitish plaques and fine blood vessels covering the centers of the corneas.

Inheritance

The pedigree pattern in the family with corneal dermoids originally reported by Henkind et al. (1973) was consistent with X-linked recessive inheritance (Dar et al., 2001).

Mapping

Igbal et al. (1987) performed linkage analysis in the family described by Henkind et al. (1973). No recombination was found between the CND locus and DXS43, which maps to Xp22.2-p22.1 (theta = 0.00; lod = 2.4).

Dar et al. (2001) reported linkage analysis in the extended family of the pedigree originally described by Henkind et al. (1973). Linkage analysis showed 2 recombination events between the disease locus and the marker at DXS43pD2 in 2 previously untested individuals. Linkage at the previously defined locus at Xp22.1-p22.3 was excluded. A 2-point lod score of 2.9 was obtained for the markers at DXS102, DXS1232, and DXS8377 (theta = 0.00). The centromeric boundary was defined by the marker at DXS1001 on Xq24, and no crossovers during recombination events were identified between the markers at DXS8057 and DXS8377, an approximately 38-cM interval. Multipoint linkage analysis gave a maximum lod score of 2.92 for the interval between the markers at DXS1062 and DXS8028, an approximately 25-cM interval, a physical distance of approximately 3.7 Mb. This analysis localized the gene for the CND phenotype in the region Xq24-qter.

Symptoms

Eyes: Corneal dermoid; Congenital opaque corneas

Inheritance: X-linked
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Van den ende-gupta syndrome

Retrieved: 27-07-2015
Source: OMIM (Original article)
Associated genes: scarf2

Description

A number sign (#) is used with this entry because of evidence that van den Ende-Gupta syndrome (VDEGS) is caused by homozygous mutation in the SCARF2 gene (613619) on chromosome 22q11.Van den Ende-Gupta syndrome is an autosomal recessive disorder characterized by severe contractual arachnodactyly from birth and distinctive facial dysmorphism, including triangular face, malar hypoplasia, narrow nose, everted lips, and blepharophimosis. Skeletal anomalies include slender ribs, hooked clavicles, and dislocated radial head. There is no neurologic involvement (summary by Patel et al., 2014).

Clinical features

In a Brazilian girl born of consanguineous parents, van den Ende et al. (1992) described a Marden-Walker-like disorder, which differed from the usual Marden-Walker syndrome (248700) by the absence of microcephaly, mental retardation, muscular hypotonia, failure to thrive, and joint limitation.

Gupta et al. (1995) described a girl of Pakistani origin, also born to consanguineous parents, with a similar multiple congenital anomaly (MCA) syndrome. The hallmarks of the syndrome included characteristic facies with blepharophimosis, narrow and beaked nose, hypoplastic maxilla with or without cleft palate and everted lower lip, arachnodactyly, self-limi...

Symptoms

INHERITANCE: Autosomal recessive

HEAD AND NECK: [Face]; Malar hypoplasia; Asymmetric face; [Ears]; Prominent ears; [Eyes]; Blepharophimosis; Downslanting eyebrows; Sclerocornea (in some patients); [Nose]; Narrow nose; Hypoplastic alae nasi; Flat nasal bridge; Post-choanal stenosis; Pseudocleft of the columella; [Mouth]; Everted lower lip; High arched palate; Cleft palate; [Teeth]; Dental crowding

RESPIRATORY: [Nasopharynx]; Tightly coiled epiglottis; Shortened aryepiglottic folds; [Larynx]; Laryngomalacia; Stridor; Globular cuneiform cartilage

CHEST: [Ribs, sternum, clavicles, and scapulae]; Slender ribs; Hooked clavicles; Hypoplastic glenoid fossa; Pectus excavatum

SKELETAL: Joint contractures (improves with time); [Skull]; Small anterior cranial fossa; Maxillary hypoplasia; Craniosynostosis; [Limbs]; Elbow contractures; Knee contractures; Dislocated radial head; Ulnar bowing; Slender long bones; Femoral bowing; Distal shortening of ulna; [Hands]; Slender hands; Arachnodactyly; Camptodactyly; Hypoplastic distal digital creases; Long thumbs; Long, slender metacarpals; Long, slender phalanges; [Feet]; Slender feet; Long halluces; Clubfeet; Hallux valgus; Camptodactyly

SKIN, NAILS, HAIR: [Hair]; Downslanting eyebrows

NEUROLOGIC: [Central nervous system]; Cerebellar enlargement; Normal intelligence

PRENATAL MANIFESTATIONS: [Placenta and umbilical cord]; Single umbilical artery

MOLECULAR BASIS: Caused by mutation in the scavenger receptor class F, member 2 gene (SCARF2, 613619.0001)
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Van den Ende-Gupta syndrome

Retrieved: 27-07-2015
Source: Orphanet (Original article)
Associated genes: scarf2

Van den Ende-Gupta syndrome is a very rare syndrome characterized by blepharophimosis, arachnodactyly, joint contractures, and characteristic dysmorphic features. Ten cases from seven families have been reported in the literature. The dysmorphic features include narrow nose with hypoplastic alae nasi, hypoplastic maxilla, everted lower lip, blepharophimosis, large ears and high-arched or cleft palate. The affected patients can have learning disabilities. The condition is transmitted as an autosomal recessive trait. Last update: October 2010

Yunis–Varon syndrome

Retrieved: 27-07-2015
Source: WIKIPEDIA (Original article)
Associated genes: fig4
Yunis–Varon syndrome (YVS), also called cleidocranial dysplasia with micrognathia, absent thumbs and distal aphalangia, is an extremely rare autosomal recessive multisystem congenital disorderYunis Varon Syndrome which affects the skeletal system, ectodermal tissue, heart and respiratory system.

Characteristics

Features of YVS include growth retardation before and after birth, defective growth of the bones of the skull along with complete or partial absence of the shoulder blades and characteristic facial features. Additional symptoms may include abnormalities of the fingers and/or toes. In most cases, infants with this disorder experience severe feeding problems and respiratory difficulties. In addition, affected infants may have heart defects.

Genetics

This syndrome is inherited in an autosomal recessive manner.

Epidemiology

YVS has been described relatively recently in the 1980s and since then less than 15 cases have been reported around the world. Many of the infants did not survive beyond one year of age.
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Norrie disease

Retrieved: 27-07-2015
Source: GARD (Original article)
Norrie disease

Norrie disease

Norrie disease is an inherited eye disorder that leads to blindness in male infants at birth or soon after birth. Additional symptoms may occur in some cases, although this varies even among individuals in the same family. Some affected individuals may develop hearing loss and exhibit cognitive abnormalities such as developmental delays or behavioral issues. Mutations in the NDP gene cause Norrie disease. It is inherited in an X-linked recessive pattern
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Norrie disease

Retrieved: 27-07-2015
Source: GHR (Original article)
Norrie disease

What is Norrie disease?

Norrie disease is an inherited eye disorder that leads to blindness in male infants at birth or soon after birth. It causes abnormal development of the retina, the layer of sensory cells that detect light and color, with masses of immature retinal cells accumulating at the back of the eye. As a result, the pupils appear white when light is shone on them, a sign called leukocoria. The irises (colored portions of the eyes) or the entire eyeballs may shrink and deteriorate during the first months of life, and cataracts (cloudiness in the lens of the eye) may eventually develop. About one third of individuals with Norrie disease develop progressive hearing loss, and more than half experience developmental delays in motor skills such as sitting up and walking. Other problems may include mild to moderate intellectual disability, often with psychosis, and abnormalities that can affect circulation, breathing, digestion, excretion, or reproduction.

How common is Norrie disease?

Norrie disease is a rare disorder; its exact incidence is unknown. It is not associated with any specific racial or ethnic group.

What genes are related to Norrie disease?

Mutations in the NDP gene cause Norrie disease. The NDP gene provides instructions for making a protein called norrin. Norrin participates in the Wnt cascade, a sequence of steps that affect the way cells and tissues develop. In particular, norrin seems to play a critical role in the specialization of retinal cells for their unique sensory capabilities. It is also involved in the establishment of a blood supply to tissues of the retina and the inner ear, and the development of other body systems. In order to initiate the Wnt cascade, norrin must bind (attach) to another protein called frizzled-4. Mutations in the norrin protein interfere with its ability to bind to frizzled-4, resulting in the signs and symptoms of Norrie disease. Read more about the NDP gene.

How do people inherit Norrie disease?

This condition is inherited in an X-linked recessive pattern. A condition is considered X-l...

Keywords

Norrie disease,Eye Diseases, Hereditary,Genetic Diseases, Inborn,Congenital, Hereditary, and Neonatal Diseases and Abnormalities,Eye Diseases,Eyes and vision,vitreoretinal dysplasia,NDP,NDP gene,Anderson-Warburg syndrome,Atrophia bulborum hereditaria,congenital progressive oculo-acoustico-cerebral degeneration,Episkopi blindness,Fetal iritis syndrome,Norrie's disease,Norrie syndrome,Norrie-Warburg syndrome,Oligophrenia microphthalmus,pseudoglioma congenita,Whitnall-Norman syndrome,National Library of Medicine,NLM,National Institutes of Health,NIH,health problem,health problems,disease,diseases,human genetics,gene,genes,genetic disease,genetic conditions,genetic disorders,medical genetics,genetics education,genetics glossary,gene reference,genetics reference,human genetic health,genomic medicine,molecular medicine,genetic testing,genomic medicine,gene therapy,pharmacogenomics,genetic counseling,counseling,gene testing,genome,hereditary family history,future of medicine,Disease and Gene Association
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Gorlin-Chaudhry-Moss syndrome

Retrieved: 27-07-2015
Source: Orphanet (Original article)

Gorlin-Chaudhry-Moss (GCM) syndrome is a multiple congenital anomaly syndrome, characterized by craniofacial dysostosis, facial dysmorphism, conductive hearing loss, generalized hypertrichosis, hypoplasia of labia majora, and extremity, ocular and dental anomalies. To date, 7 cases of GCM have been described in the world literature and all patients are female with no known parental consanguinity. GCM is a congenital disorder in which patients present with a stocky body build, normal intelligence, coronal craniosynostosis, facial dysmorphism (brachy/turricephaly, low anterior and posterior hairline, coarse hair, synophrys, depressed supraorbital riddges, short, downslanted or upslanted palpebral fissures, ectropion of lower eyelid, underdeveloped ala nasi, prominent columella, midface hypoplasia, and underdeveloped small ears with increased posterior angulation), conductive hearing loss, ocular (coloboma of the eyelid (see this term), hyperopia, microphthalmia,) and oro-dental (microdontia, irregularly shaped widely spaced teeth, oligodontia (see this term), narrow, and high arched narrow palate with medial cleft) anomalies and generalized hypertrichosis. Extremity anomalies (hypoplastic distal phalanges, small/aplastic nails, cutaneous syndactyly, absent flexion crease of the thumbs, single transverse palmar creases), umbilical hernia, and hypoplasia of labia majora are also observed. Other additional features that may be observed include congenital laryngomalacia and heart disease (patent arterial duct) (see these terms). Progeroid syndrome, Petty type and Saethre-Chotzen syndrome (see these terms) have overlapping features with GCM syndrome and should be considered in the differential diagnosis. The etiology is still unknown and to date, no causative gene has been implicated in the physiopathology of GCM. GCM is considered to be inherited in an autosomal recessive manner. However, the lack of consanguinity combined with the fact that all affected patients...
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Gorlin-chaudhry-moss syndrome

Retrieved: 27-07-2015
Source: OMIM (Original article)

Clinical features

Gorlin et al. (1960) described 2 sisters with craniofacial dysostosis, patent ductus arterious, hypertrichosis, genital hypoplasia, and ocular, dental, and digital anomalies. The parents were not known to be related. The same sisters were reported by Feinberg (1960) as instances of the Weill-Marchesani syndrome (277600), which was clearly an incorrect diagnosis. Gorlin (1977) had seen no further cases of this syndrome and knew of no others in the literature. Ippel et al. (1992) provided follow-up of the 2 sisters reported by Gorlin et al. (1960), G.G. and N.G., then aged 36 and 34, respectively. Although there had been slight coarsening of the facial features with time, the overall clinical picture had not changed. They reported 2 additional patients, both female, aged 4 and 33 years. All 4 patients had conductive hearing loss, hypertrichosis, coarse hair, and low frontal hairline. The 2 new patients had very short distal phalanges of fingers and toes. As in the original patients, G.G. and N.G. (as reported by Feinberg, 1960), the skeletal abnormalities included shortened metacarpals and distal phalanges. Parental consanguinity has not been established in any of these patients.

Preis et al. (1995) pointed out phenotypic overlap between the GCM syndrome and the Saethre-Chotzen syndrome (101400).

Symptoms

INHERITANCE: Autosomal recessive

GROWTH: [Height]; Short stature; [Other]; Stocky body build

HEAD AND NECK: [Head]; Brachycephaly; [Face]; Midface hypoplasia; Depressed supraorbital ridge; [Ears]; Conductive hearing loss; [Eyes]; Downslanting palpebral fissures; Upper eyelid colobomas; Microphthalmia; Hyperopia; Hypertelorism; Ptosis; [Mouth]; High-arched palate; Narrow palate; [Teeth]; Malocclusion; Hypodontia; Microdontia; Abnormally shaped teeth

CARDIOVASCULAR: [Vascular]; Patent ductus arteriosus

ABDOMEN: [External features]; Umbilical hernia

GENITOURINARY: [External genitalia, female]; Hypoplastic labia majora

SKELETAL: [Skull]; Craniosynostosis (coronal); Clival hypoplasia; Elevation of the lessor sphenoidal wings; Hypoplastic maxillary bones; Hypoplastic nasal bones; [Hands]; Hypoplastic distal phalanges; [Feet]; Hypoplastic distal phalanges

SKIN, NAILS, HAIR: [Skin]; Hypertrichosis (scalp, arms, legs, back); [Hair]; Hypertrichosis (scalp, arms, legs, back)
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Axenfeld-Rieger syndrome

Retrieved: 27-07-2015
Source: Orphanet (Original article)

Axenfeld-Rieger syndrome (ARS) is a generic term used to designate overlapping genetic disorders, in which the major physical condition is anterior segment dysgenesis of the eye. Patients with ARS may also present with multiple variable congenital anomalies. The syndrome has an estimated prevalence of 1/200,000. The clinical manifestations of ARS are highly variable. Features can be divided into ocular and non-ocular findings. Ocular abnormalities mainly affect the iris: hypoplasia, corectopia or hole formation in the iris mimicking polycoria; cornea: prominent and anteriorly displaced Schwalbe's line (posterior embryotoxon); and the chamber angle: iris strands bridging the iridocorneal angle to the trabecular meshwork. Eye dysgenesis in ARS may cause increased ocular pressure (IOP) leading to glaucoma. Glaucoma can develop in infancy, but usually occurs in adolescence or early adulthood, occasionally after middle age. The most characteristic non-ocular findings are mild craniofacial dysmorphism, dental anomalies and redundant periumblical skin. Mid-face abnormalities include hypertelorism, telecanthus, maxillary hypoplasia with flattening of the mid-face, prominent forehead, and broad, flat nasal bridge. Dental abnormalities may include microdontia or hypodontia. Hypospadias in males, anal stenosis, pituitary abnormalities and growth retardation may also be observed. Patients with ARS have been found to have mutations in the transcription factor genes PITX2 (4q25) and FOXC1 (6p25). A large number of different mutations have been identified but there is no clear genotype-phenotype relationship. However, PITX2 mutations are mainly detected in ARS patients with non-ocular changes. The underlying genetic defect is unknown in 60% of cases, and at least two more loci have been associated with ARS. ARS is diagnosed by ophthalmologic and clinical examination. Associated systemic findings are supportive of diagnosis. Genetic testing can be used to confirm the diagn...
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PHACE syndrome

Retrieved: 27-07-2015
Source: Orphanet (Original article)

PHACE is an acronym used to describe a syndrome characterised by the association of Posterior fossa brain malformations, large facial Haemangiomas, anatomical anomalies of the cerebral Arteries, aortic coarctation and other Cardiac anomalies, and Eye abnormalities. Sternal anomalies are also sometimes present, and in these cases the syndrome is referred to as PHACES. Two additional manifestations have recently been added to the clinical spectrum of PHACE syndrome: stenosis of the vessels at the base of the skull and segmental longitudinal dilations of the internal carotid artery. This association of manifestations is rare and less than 100 cases have been reported in the literature so far. Expression of the complete clinical picture of PHACE syndrome is extremely rare and most patients display only a partial phenotype (or incomplete clinical spectrum). The syndrome is much more common in females than in males (8:1) and affects newborns and infants. The posterior fossa malformations include cerebellar hypoplasia, arachnoid cysts, cortical dysgenesis and Dandy-Walker malformation. The capillary haemangiomas have the same morphological, clinical and evolutive characteristics as those of sporadic benign haemangiomas. Intracranial and subarachnoid lesions may occur concurrently, with the intracranial lesions evolving in the same manner as the maxillofacial or cervical haemangiomas. Two types of arterial anomalies have been described: persistence of embryological arteries and agenesis of the carotid or vertebral artery. These anatomical arrangements allow normal cerebral function but limit the capacity for collateral circulation in case of an associated occlusive or stenotic lesion. The ophthalmological anomalies include glaucoma, coloboma, microphthalmia, cryptophthalmia and optic nerve hypoplasia. In most cases, the vascular lesions are uni- and homolateral, indicating that PHACE syndrome is a member of the group of cerebrofacial syndromes with involvement of s...
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Strabismus

Retrieved: 27-07-2015
Source: WIKIPEDIA (Original article)
Strabismus Strabismus (, from Greek strabismósOnline Etymology Dictionary), also known as heterotropia (and including the three variants cross-eye, lazy-eye and walleye),http:// www.merriam-webster.com/dictionary/strabismus is a condition in which the eyes are not properly aligned with each other. It typically involves a lack of coordination between the extraocular muscles, which prevents bringing the gaze of each eye to the same point in space and thus hampers proper binocular vision, and which may adversely affect depth perception. Strabismus can present as manifest (heterotropia) or latent (heterophoria) varieties, and can be either a disorder of the brain in coordinating the eyes, or of the power or direction of motion of one or more of the relevant muscles moving the eye. Strabismus is primarily managed by ophthalmologists, optometrists and orthoptists. Strabismus is present in about 4% of children. Treatment should be started as soon as possible to ensure the best possible visual acu...

Signs and symptoms

One eye moves normally, while the other points in (esotropia), out (exotropia), up (hypertropia) or down (hypotropia). Strabismus may be associated with "lazy eye" or "amblyopia" which is due to brain's ignoring input from one eye. Amblyopia results in impaired vision in the affected eye. During the first 7–8 years of life the brain learns how to interpret the signals that come from an eye. This process which is called visual development may be interrupted by strabismus. This is because the deviated eye is not used to focus, and the brain does not receive signals from this eye which causes failure in the normal visual development of the affected eye in childhood. "Cross-eyed" means that when a person with strabismus looks at an object, one eye fixes on the object and the other fixes with a convergence angle less than zero; the visual axes over-converge. "Wall-eyed" means that when a person with strabismus looks at an object, one eye fixes on the object and the other fixes with a convergence angle greater than zero; that is, the visual axes diverge from parallel. Non-paretic squints are generally concomitant, which means that the amount of deviation remains the same in all directions of gaze.Definition by TheFreeDictionary Nonparetic squints are not caused by a lesion reducing innervation. The squint may be associated with refractive error in one or both eyes. This refractive error causes poor vision in one eye and so stops the brain from being able to use both eyes together.

Diagnosis

During eye examination, a test which is called cover test, is typically used in the diagnosis and measurement of strabismus. If the eye being tested is the strabismic eye, then it will fixate on the object after the "straight" eye is covered, as long as the vision in this eye is good enough. If the "straight" eye is being tested, there will be no change in fixation, as it is already fixated. Depending on the direction that the strabismic eye deviates, the dir...
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Meckel syndrome

Retrieved: 27-07-2015
Source: Orphanet (Original article)
Meckel syndrome

Meckel syndrome (MKS) is a rare, lethal, genetic, multiple congenital anomaly disorder characterized by the triad of brain malformation mainly occipital encephalocele (see this term), large polycystic kidneys, and polydactyly as well as associated abnormalities that may include cleft lip/palate (see these terms), cardiac and genital anomalies, central nervous system (CNS) malformations, liver fibrosis, and bone dysplasia. Prevalence is estimated at 1/50,000 births in Europe. Worldwide prevalence is reported to be 1/13,250 to 1/140,000 live births. The live-birth prevalence is significantly higher in the Finnish population (1/9,000), Belgian and Kuwaiti Bedouin populations (1/3,500), and Gujarati Indians (1/1,300). No gender or ethnic predilection is reported. Fetuses affected by MKS survive only a few days to a few weeks at the most, or die in utero. The main CNS features include occipital encephalocele, hydrocephalus, anencephaly, holoprosencephaly, as well as Dandy-Walker (see these terms). Large polycystic kidneys with cystic dysplasia are a constant feature of Meckel syndrome. Hepatic dysgenesis and liver fibrosis are frequent. Polydactyly may affect all four extremities and is typically postaxial (80%) or very rarely preaxial. Affected individuals have pulmonary hypoplasia secondary to oligohydramnios. Cleft lip and palate, microphthalmia and micrognathia may be observed. Cardiac malformations may include atrial septal defect, aorta coarctation, patent arterial duct, and valvular pulmonary stenosis (see these terms). Incomplete development of internal and external genitalia, and cryptorchidism in males are common. Defective ciliary biology underlies MKS. Mutations in 14 cilia-related genes have been associated with this disorder, often in the context of consanguineous unions. Most of these genes are also responsible for Joubert syndrome (see this term), leading to the concept that MKS is the extreme lethal phenotype of Joubert syndrome. Diagnosis may b...

Linear skin defects with multiple congenital anomalies 3

Retrieved: 27-07-2015
Source: OMIM (Original article)

Clinical features

A number sign (#) is used with this entry because of evidence that linear skin defects with multiple congenital anomalies-3 (LSDMCA3) is caused by heterozygous mutation in the NDUFB11 gene (300403) on chromosome Xp11.3.

For a discussion of genetic heterogeneity of linear skin defects with multiple congenital anomalies, see LSDMCA1 (309801).Van Rahden et al. (2015) reported 2 unrelated girls with linear skin defects of the face and neck at birth, cardiomyopathy, and various other congenital anomalies. In 1 patient, the skin defects disappeared within the first few months of life; she also exhibited axial hypotonia and failure to thrive. Ocular examination showed lacrimal duct atresia. At 6 months of age, she was hospitalized after cardiac arrest and underwent repeated treatment of ventricular fibrillation and tachycardia, but died within a few weeks. Autopsy revealed histiocytoid cardiomyopathy and thyroid abnormalities, including sites of oncocytic metaplasia and C-cell hyperplasia. The other patient had corpus callosum agenesis and dilated lateral ventricles diagnosed on prenatal ultrasound. At 2 months of age, she had seizures and also developed dilated cardiomyopathy, for which she underwent cardiac transplantation at age 6 months. Eye examination at age 15 months showed myopia, nystagmus, and strabismus. Severe psychomotor delay became evident over time; she started walking at age 3 years and could speak simple sentences and had sphincter control by age 7 years. Severe muscular hypotonia and delayed dentition were also present. Neither p...

Symptoms

INHERITANCE: X-linked dominant

GROWTH: [Other]; Failure to thrive

HEAD AND NECK: [Face]; Linear skin defects on face at birth (in both patients); [Eyes]; Lacrimal duct atresia; Myopia; Nystagmus; Strabismus; [Teeth]; Delayed dentition; [Neck]; Linear skin defects on neck at birth (in both patients)

CARDIOVASCULAR: [Heart]; Cardiomyopathy, histiocytoid; Cardiomyopathy, dilated; Ventricular tachycardia; Ventricular fibrillation; Cardiac arrest

SKIN, NAILS, HAIR: [Skin]; Linear skin defects on face and neck (in both patients); Atrophic hyperpigmented streaks on face and neck; Linear atrophic hyperpigmented streak on left index finger

MUSCLE, SOFT TISSUE: Muscular hypotonia, severe

NEUROLOGIC: [Central nervous system]; Axial hypotonia; Seizures; Corpus callosum agenesis; Dilation of lateral ventricles

METABOLIC FEATURES: Normal blood lactate levels (in both patients)

ENDOCRINE FEATURES: Thyroid oncocytic metaplasia; C-cell hyperplasia

MISCELLANEOUS: Based on report of 2 unrelated patients (last curated May 2015); Skewed X-inactivation, with complete skewing in some individuals; Congenital linear skin defects may disappear within a few months of life

MOLECULAR BASIS: Caused by mutation in the NADH dehydrogenase-1 beta subcomplex-11 gene (NDUFB11, 300403.0001)

Retrieved: 27-07-2015
Source: WIKIPEDIA (original)
Associated genes: dgs2, dgcr2, celf2
Thymic hypoplasia is a condition where the thymus is underdeveloped or involuted. Calcium levels can be used to distinguish between the following two conditions associated with thymic hypoplasia: 22q11.2 deletion syndrome: hypocalcemia Ataxia telangiectasia: normal levels of calcium


Retrieved: 27-07-2015
Source: OMIM (original)

Description

Sclerocornea is a primary anomaly in which scleralization of a peripheral part of the cornea, or the entire corneal tissue, occurs. In the peripheral type, the affected area is vascularized with regular arcades of superficial scleral vessels. In total sclerocornea, the entire cornea is opaque and vascularized (summary by Elliott et al., 1985).

Clinical features

Elliott et al. (1985) reported a 5-generation family in which 9 members had peripheral sclerocornea. All affected members also had autosomal dominant cornea plana (121400), and some had glaucoma, corneal degeneration, posterior embryotoxon, cataract, microphthalmia, nystagmus, esotropia, iris heterochromia, and amblyopia.

Inheritance

Elliott et al. (1985) reported a 5-generation family in which 9 members had peripheral sclerocornea and cornea plana. The pedigree pattern was consistent with autosomal dominant inheritance. They identified 4 reported pedigrees (25 patients) in which peripheral sclerocornea and cornea plana were inherited in an autosomal dominant manner.

From a review of the literature, Elliott et al. (1985) suggested that the autosomal dominant form of sclerocornea is mild, whereas an autosomal recessive form (269400), which is also associated with cornea plana (217300), is severe.

Symptoms

Eyes: Congenital sclerocornea

Inheritance: Autosomal dominant form

22q11.2 deletion syndrome

22q11.2 deletion syndrome is a spectrum disorder that includes conditions formerly called DiGeorge syndrome; velocardiofacial syndrome; conotruncal anomaly face syndrome; cases of Opitz G/BBB syndrome; and Cayler cardiofacial syndrome. The features and severity can vary greatly among affected people. Signs and symptoms may include cleft palate, heart defects, recurrent infections, unique facial characteristics, feeding problems, immune system disorders, kidney abnormalities, hypoparathyroidism, thrombocytopenia, scoliosis, hearing loss, developmental delay, and learning disabilities. People with this condition are also more likely to develop certain autoimmune disorders and personality disorders. In most cases, the syndrome occurs for the first time in the affected person; about 10% of cases are inherited from a parent. It is inherited in an autosomal dominant manner


Retrieved: 27-07-2015
Source: WIKIPEDIA (original)
Associated genes: rax, prkra, lbx1
Sclerocornea is a congenital anomaly of the eye in which the cornea blends with sclera, having no clear-cut boundary. The extent of the resulting opacity varies from peripheral to total (sclerocornea totalis). The severe form is thought to be inherited in an autosomal recessive manner, but there may be another, milder form that is expressed in a dominant fashion. In some cases the patients also have abnormalities beyond the eye (systemic), such as limb deformities and craniofacial and genitourinary defects. According to one tissue analysis performed after corneal transplantation, the sulfation pattern of keratan sulfate proteoglycans in the affected area is typical for corneal rather than scleral tissue. Sclerocornea may be concurrent with cornea plana.

External links

Congenital Clouding of the Cornea - eMedicine; by Noah S Scheinfeld, MD, JD, FAAD and Benjamin D Freilich, MD, FACS


Retrieved: 27-07-2015
Source: Orphanet (original)

Episodic ataxia type 4 (EA4) is a very rare form of Hereditary episodic ataxia (see this term) characterized by late-onset episodic ataxia, recurrent attacks of vertigo, and diplopia. Last update: January 2014


Retrieved: 27-07-2015
Source: OMIM (original)
Associated genes: pxdn

Description

A number sign (#) is used with this entry because of evidence that corneal opacification associated with other ocular anomalies, such as cataract, microcornea, microphthalmia, and anterior segment dysgenesis, is caused by homozygous or compound heterozygous mutation in the PXDN gene (605158) on chromosome 2p25.In sclerocornea there is congenital, nonprogressive corneal opacification that may be peripheral, sectoral, or central in location. Visual prognosis is related to the central corneal involvement. The cornea has a flat curvature. The majority of cases are bilateral (summary by Smith and Traboulsi, 2012).

Isolated sclerocornea is caused by displacement of the limbal arcades and may be associated with cornea plana; in this condition, the anterior chamber is visible and the eye is not microphthalmic. In complex sclerocornea, however, corneal opacification is associated with microphthalmia, cataract, and/or infantile glaucoma. The central cornea is usually relatively clear, but the thickness is normal or increased, never reduced (summary by Nischal, 2007).

Clinical features

Khan et al. (2011) studied a consanguineous Pakistani family (family MEP60) segregating autosomal recessive cataract, microcornea, and corneal opacity, which the authors designated CCMCO. The 3 affected family members exhibited corneas that were 7 to 8 mm in diameter, and anterior segment examination showed that the peripherally located corneal opacity appeared to be due to the sclera encroaching on the cornea. Peripheral iridocorneal adhesion was also present. Vision was reduced to counting fingers in all 3 patients. The family history suggested that the changes were not progressive.

Khan et al. (2011) reported a large consanguineous Pakistani family (family MEP59) in which 4 sibs and 2 cousins had corneal opacification as well as cataract and microcornea. The lens was of normal size and shape, and the fundus was normal by indirect ophthalmoscopy. Khan et al. (2011) also described a consanguineous Cambodian family (family CA2) with 4 affected sibs who had severe corneal opacification, 3 of whom also had bilateral buphthalmos and exhibited severe vascularization of the cornea. Elevated intraocular pressures were present in 3 of the sibs, including the patient without buphthalmos. The extent of corneal opacification prevented visualization of the anterior chamber or fundus, and the presence or absence of cataract could not be deter...

Symptoms

INHERITANCE: Autosomal recessive

HEAD AND NECK: [Eyes]; Corneal opacification, partial or total; Sclerocornea (in some patients); Cataract (in some patients); Microcornea (in some patients); Iridocorneal dysgenesis (in some patients); Increased intraocular pressure (in some patients); Buphthalmos (in some patients); Microphthalmia (in some patients); Anterior segment dysgenesis (in some patients)

MOLECULAR BASIS: Caused by mutation in the homolog of Drosophila peroxidasin gene (PXDN, 605158.0001)


Retrieved: 27-07-2015
Source: Orphanet (original)
Associated genes: pi4ka

22q11.2 deletion syndrome (DS) is a chromosomal anomaly which causes a congenital malformation disorder whose common features include cardiac defects, palatal anomalies, facial dysmorphism, developmental delay and immune deficiency. The worldwide incidence is estimated at 1/2,000-1/4,000 live births. 22q11.2 DS shows a variable clinical phenotype that can range from mild to severe. Congenital heart defects (77% of cases) include mainly conotruncal malformations such as truncus arteriosus, tetralogy of Fallot and vetricular septal defect. More than 75% of patients present with palatal anomalies (e.g. overt cleft palate, cleft lip and palate, velopharyngeal incompetence) that may lead to hypernasal speech, feeding and swallowing difficulties. Developmental delay is frequent. Many patients present with mild facial dysmorphism (e.g. malar flatness, ptosis, hypertelorism, epicanthal folds, prominent nasal root) and vertebral anomalies (e.g. butterfly vertebrae, hemivertebrae). 75% of patients have an immune deficiency due to thymic aplasia/hypoplasia that renders them susceptible to various infections. Patients also have a higher risk of developing an autoimmune disease such as idiopathic thrombocytopenic purpura and juvenile idiopathic arthritis (see these terms). Neonatal hypocalcemia is observed in 50% of cases. It usually resolves but can reappear at any age or after an infection, surgery or pregnancy. Additional clinical findings may include gastrointestinal anomalies (intestinal malrotation, imperforate anus), hearing loss, renal anomalies (renal agenesis), dental anomalies (enamel hypoplasia), learning problems and/or psychiatric disorders (attention deficit hyperactivity disorder, schizophrenia). The broad spectrum of clinical phenotypes that the syndrome encompasses was previously divided into distinct syndromes (e.g. DiGeorge syndrome, velocardiofacial syndrome, cardiofacial syndrome) but are now known to be etiologically identical and are referred to ...


Retrieved: 27-07-2015
Source: Orphanet (original)
Associated genes: foxe3

Congenital primary aphakia (CPA) is characterised by an absence of the lens. The prevalence is unknown. CPA can be associated with variable secondary ocular defects (including aplasia/dysplasia of the anterior segment of the eye, microphthalmia, and in some cases absence of the iris, retinal dysplasia, or sclerocornea). CPA results from early developmental arrest, around the 4th-5th week of embryogenesis, which prevents the formation of any lens structure. Mutations in the FOXE3 gene were identified in three affected siblings born to consanguineous parents. Last update: December 2006


Retrieved: 27-07-2015
Source: OMIM (original)

Description

On the island of Rodrigues in the Indian Ocean, Wallis and Beighton (1992) identified a brother and sister with moderately severe mental retardation, blindness due to severe ocular malformations (microphthalmia, microcornea, and sclerocornea), short stature, dysmorphic facial features (narrow nasal bridge with distal flaring of the nose and prominent ears), fine and sparse hair, and malaligned teeth. Wallis and Beighton (1992) emphasized, possibly inappropriately, the hair and dental changes in entitling their report.

Symptoms

Neuro: Mental retardation

Eyes: Blindness; Microphthalmos; Microcornea; Sclerocornea

Growth: Short stature

Facies: Dysmorphic facial features; Narrow nasal bridge; Distal nasal flaring; Prominent ears

Hair: Fine hair; Sparse hair

Teeth: Malaligned teeth

Inheritance: Autosomal recessive


Retrieved: 27-07-2015
Source: OMIM (original)
Associated genes: scn8a

Clinical features

A number sign (#) is used with this entry because of evidence that cognitive impairment with or without cerebellar ataxia is caused by heterozygous mutation in the SCN8A gene (600702) on chromosome 12q13. One such family has been reported.Trudeau et al. (2006) reported a family of Swedish and Norwegian origin with highly variable neurologic deficits. The proband was a 9-year-old boy with markedly delayed psychomotor development, attention deficit disorder, and cerebellar ataxia. Features included ataxic wide-based gait, dysmetria in the upper limbs, and dysarthria, with normal strength, tone, and reflexes. He also had esophoria, amblyopia, and gaze-evoked nystagmus. Brain MRI showed moderate pancerebellar atrophy, accentuated in the vermal and parasagittal regions, as well as optic nerve hypoplasia. There were no cerebral abnormalities. His mother and maternal aunt had a history of emotional instability and mild cognitive impairment, and a first cousin had attention deficit-hyperactivity disorder (ADHD; 143465). A brother of the proband was noted to have impaired cognition and another cousin was noted to have ADHD, but they were not studied at the molecular level. In addition, none of the family members besides the proband was available for formal clinical evaluation or brain imaging studies. The proband was ascertained during a study of 151 patients with ataxia who were screened specifically for mutations in the SCN8A gene (see MOLECULAR GENETICS).

Molecular genetics

Because SCN8A is widely expressed in neurons of the central and peripheral nervous systems, and because mutations in the mouse ortholog result in ataxia and other movement disorders, Trudeau et al. (2006) screened the 26 coding exons of SCN8A in 151 patients with inherited or sporadic ataxia and no mutations in known ataxia-related genes. They found a heterozygous 2-bp deletion in exon 24 (600702.0001) in a 9-year-old boy with mental retardation, pancerebellar atrophy, and ataxia. Three additional family members who were heterozygous for this mutation exhibited milder cognitive behavioral deficits including ADHD. However, Trudeau e...

Symptoms

INHERITANCE: Autosomal dominant

HEAD AND NECK: [Eyes]; Optic nerve hypoplasia (1 patient); Gaze-evoked nystagmus (1 patient); Esophoria (1 patient); Amblyopia (1 patient)

NEUROLOGIC: [Central nervous system]; Cognitive impairment (3 patients); Mental retardation (1 patient); Ataxia (1 patient); Dysmetria (1 patient); Dysarthria (1 patient); Brain MRI shows cerebellar atrophy (1 patient); [Behavioral/psychiatric manifestations]; Attention deficit-hyperactivity disorder (3 patients); Emotional lability (2 patients)

MISCELLANEOUS: Three patients in one family have been reported (as of October 2011), and only one mutation carrier exhibited mental retardation and ataxia

MOLECULAR BASIS: Caused by mutation in the voltage-gated sodium channel, type VIII, alpha subunit gene (SCN8A, 600702.0001)

22q11.2 deletion syndrome, which has several presentations including DiGeorge syndrome (DGS), DiGeorge anomaly, velo-cardio-facial syndrome, Shprintzen syndrome, conotruncal anomaly face syndrome, Strong syndrome, congenital thymic aplasia, and thymic hypoplasia, is a syndrome caused by the deletion of a small piece of chromosome 22. The deletion occurs near the middle of the chromosome at a location designated 22q11.2—signifying its location on the long arm of one of the pair of chromosomes 22, on region 1, band 1, sub-band 2. It has a prevalence estimated at 1:4000. The syndrome was described in 1968 by the pediatric endocrinologist Angelo DiGeorge.DiGeorge AM. Congenital absence of the thymus and its immunologic consequences: concurrence with congenital hypoparathyroidism. IV(1). White Plains, NY: March of Dimes-Birth Defects Foundation; 1968:116-21 22q11 deletion is also associated with truncus arteriosus (see TOF).

Presentation

The features of this syndrome vary widely, even among members of the same family, and affect many parts of the body. Characteristic signs and symptoms may include birth defects such as congenital heart disease, defects in the palate, most commonly related to neuromuscular problems with closure (velo-pharyngeal insufficiency), learning disabilities, mild differences in facial features, and recurrent infections. Infections are common in children due to problems with the immune system's T-cell mediated response that in some patients is due to an absent or hypoplastic thymus. 22q11.2 deletion syndrome may be first spotted when an affected newborn has heart defects or convulsions from hypocalcemia due to malfunctioning parathyroid glands and low levels of parathyroid hormone (parathormone). Affected individuals may also have any other kind of birth defect including kidney abnormalities and significant feeding difficulties as babies. Disorders such as hypothyroidism and hypoparathyroidism or thrombocytopenia (low platelet levels), and psychiatric illnesses are common late-occurring features. Microdeletions in chromosomal region 22q11.2 are associated with a 20 to 30-fold increased risk of schizophrenia. Studies provide various rates of 22q11.2 deletion syndrome in schizophrenia, ranging from 0.5 to 2% and averaging about 1%, compared with the overall estimated 0.025% risk of the 22q11.2 deletion syndrome in the general population. Salient features can be summarized using the mnemonic CATCH-22 to describe DiGeorge syndrome, with the 22 to remind one the chromosomal abnormality is found on the 22 chromosome, as below: Cardiac Abnormality (especially tetralogy of Fallot)Abnormal facies Thymic aplasia Cleft palate Hypocalcemia/Hypoparathyroidism.

Nomenclature

The signs and symptoms of 22q11 deletion syndrome are so varied that different groupings of its features were once regarded as separate conditions. These original classifications included velo-cardio-facial syndrome, Shprintzen syndrome, DiGeorge sequence/syndrome, Sedlackova...


Retrieved: 27-07-2015
Source: OMIM (original)
Associated genes: rax

Nomenclature

A number sign (#) is used with this entry because of evidence that isolated microphthalmia-3 (MCOP3) is caused by compound heterozygous mutation in the RAX gene (601881) on chromosome 18q21.

For a phenotypic description and a discussion of genetic heterogeneity of isolated microphthalmia, see MCOP1 (251600).The term 'anophthalmia' has been misused in the medical literature. True or primary anophthalmia is incompatible with life; in such cases, the primary optic vesicle has stopped developing and the abnormal development involves major defects in the brain as well (Francois, 1961). The diagnosis can only be made histologically (Reddy et al., 2003; Morini et al., 2005; Smartt et al., 2005), but this is rarely done. In most published cases, the term 'anophthalmia' is used as a synonym for the more appropriate terms 'extreme microphthalmia' or 'clinical anophthalmia.'

Clinical features

Voronina et al. (2004) reported a 12-year-old boy, born to nonconsanguineous parents, who had right clinical anophthalmia and ankyloblepharon and left microphthalmia with sclerocornea. Ocular ultrasound showed a very small cystic remnant on the right and persistent fetal vasculature and total retinal detachment on the left. An EEG at 7 years of age showed abnormal slowing of background activity consistent with underlying cortical activity, and the patient was diagnosed as autistic. MRI of the brain was normal.

Molecular genetics

Voronina et al. (2004) analyzed the RAX gene in 75 individuals with clinical anophthalmia and/or microphthalmia and identified compound heterozygosity for a nonsense mutation (601881.0001) and a missense mutation (601881.0002) in a 12-year-old boy with right clinical anophthalmia and left microphthalmia who also had a diagnosis of autism.

In a 2-year-old Algerian girl with bilateral clinical anophthalmia, the third child born to nonconsanguineous parents, Lequeux et al. (2008) identified compound heterozygosity for a deletion and a nonsense mutation in the RAX gene (601881.0003 and 601881.0004, respectively). The girl had no other dysmorphic features or malformations and normal psychomotor development. MRI of the brain showed bilateral absence of eyes with fibrous tissue in the orbits and hypoplastic optic nerves and chiasma; the hypothalamus and pituitary gland were normal.

Symptoms

INHERITANCE: Autosomal recessive

HEAD AND NECK: [Eyes]; Anophthalmia, clinical; Microphthalmia; Ankyloblepharon; Sclerocornea

MOLECULAR BASIS: Caused by mutation in the retina and anterior neural fold homeobox gene (RAX, 601881.0001)


Retrieved: 27-07-2015
Source: WIKIPEDIA (original)
Microphthalmia–dermal aplasia–sclerocornea syndrome (also known as "MIDAS syndrome") is a condition characterized by linear skin lesions. It can be associated with HCCS.

See also

List of cutaneous conditions

External links

GeneReview/NIH/UW entry on Microphthalmia with Linear Skin Defects Syndrome


Retrieved: 27-07-2015
Source: OMIM (original)
Associated genes: hoxb1

Clinical features

A number sign (#) is used with this entry because of evidence that hereditary congenital facial paresis-3 (HCFP3) is caused by homozygous mutation in the HOXB1 gene (142968) on chromosome 17q21.

For a phenotypic description and a discussion of genetic heterogeneity of hereditary congenital facial paresis (HCPF), see 601471.Webb et al. (2012) studied 2 brothers, born of consanguineous parents of conservative German American background, who had previously been diagnosed with Moebius syndrome (157900). The sibs were noted to have bilateral facial weakness, sensorineural hearing loss, and esotropia in the first months of life, and developed feeding difficulties and speech delays requiring oromotor and speech therapies. Both underwent surgery to correct esotropia, and both wore glasses for high hyperopia. MRI in the older brother at 8 months of age revealed bilateral absence of the facial nerve and bilateral abnormal tapering of the basal turn of the cochlea. Auditory brainstem response testing in both boys revealed bilateral mild to moderate high frequency hearing loss with normal absolute latencies of waveforms, and distortion product otoacoustic emissions were absent in both children, supporting abnormal cochlear function. Stapedius reflexes were intact bilaterally. Examination at 7.25 years and 2.9 years of age, respectively, revealed midface retrusion, low-set and posteriorly rotated ears, upturned nasal tip, and smooth philtrum in both boys. Neither child showed any facial movement. Taste discrimination, salivation, and lacrimation were intact, as was general sensation over the concha of the ear and skin behind the auricle. Webb et al. (2012) noted that because both boys had partially accommodative esotropia with high hyperopia and full eye movements, they did not meet the criteria for Moebius syndrome. Their parents and a brother were unaffected, and there was no family history of strabismus or facial weakness.

Mapping

In 2 brothers with congenital facial paresis and their unaffected consanguineous conservative German American parents, Webb et al. (2012) performed linkage and homozygosity mapping and identified a single approximate...

Symptoms

INHERITANCE: Autosomal recessive

HEAD AND NECK: [Face]; Facial paresis, congenital bilateral; Facial muscle weakness of muscles innervated by CN VII; Midface retrusion (in some patients); Micrognathia (in some patients); Smooth philtrum (in some patients); [Ears]; Hearing loss, sensorineural, mild to moderate; Low-set ears (in some patients); Posteriorly rotated ears (in some patients); [Eyes]; Esotropia (in some patients); Esophoria (in some patients); [Nose]; Upturned nasal tip (in some patients)

NEUROLOGIC: [Central nervous system]; Facial paresis, congenital bilateral; Facial muscle weakness of muscles innervated by CN VII

MISCELLANEOUS: Nonprogressive disorder

MOLECULAR BASIS: Caused by mutation in the homeobox B1 gene (HOXB1, 142968.0001)


Retrieved: 27-07-2015
Source: Orphanet (original)
Associated genes: gja8, crybb1

Cataract-microcornea syndrome is characterized by the association of congenital cataract and microcornea without any other systemic anomaly or dysmorphism. To date, more than 15 families showing microcornea-cataract syndrome have been described. Clinical findings include a corneal diameter inferior to 10 mm in both meridians in an otherwise normal eye, and an inherited cataract, which is most often bilateral posterior polar with opacification in the lens periphery. The cataract progresses to form a total cataract after visual maturity has been achieved, requiring cataract extraction in the first to third decade of life. Microcornea-cataract syndrome can be associated with other rare ocular manifestations, including myopia, iris coloboma, sclerocornea and Peters anomaly (see this term). Transmission is in most cases autosomal dominant, but cases of autosomal recessive transmission have recently been described. There is marked genetic heterogeneity. Mutations have been described in several crystallin genes (CRYAA, CRYBB1, CRYGD), and in the gap junction protein alpha 8 gene (GJA8). Ophthalmologic and general examination allows other syndromes to be excluded. Cataract surgery has to be performed in order to restore visual acuity and avoid amblyopia. Visual acuity after uncomplicated cataract extraction is relatively good. Expert reviewer(s) Dr Alrun LEROUX-GRONEMEYER Pr Gottfried NAUMANN Last update: October 2007


Retrieved: 27-07-2015
Source: OMIM (original)
Associated genes: cyp11b2, mcop1, prss56

Description

One form of isolated microphthalmia (MCOP1) has been mapped to chromosome 14q32.Microphthalmia designates a heterogeneous group of ocular malformations with a more or less evident reduction in the size of the eyeball. Additional features include high hypermetropia and a short axial length. The size of the anterior chamber and the cornea may also be reduced, whereas the lens is normal or thicker than usual for age (summary by Fuchs et al., 2005).

- Genetic Heterogeneity of Isolated Microphthalmia

MCOP2 (610093) is caused by mutation in the CHX10 gene (142993) on chromosome 14q24. MCOP3 (611038) is caused by mutation in the RAX gene (601881) on chromosome 18q21.3. MCOP4 (613094) is caused by mutation in the GDF6 gene (601147) on chromosome 8q22.1. MCOP5 (611040) is caused by mutation in the MFRP gene (606227) on chromosome 11q23. MCOP6 (613517) is caused by mutation in the PRSS56 gene (613858) on chromosome 2q37.1. MCOP7 (613704) is caused by mutation in the GDF3 gene (606522) on chromosome 12p13.1. MCOP8 (615113) is caused by mutation in the ALDH1A3 gene (600463) on chromosome 15q26.

Nomenclature

The term 'anophthalmia' has been misused in the medical literature. True or primary anophthalmia is incompatible with life; in such cases, the primary optic vesicle has stopped developing and the abnormal development involves major defects in the brain as well (Francois, 1961). The diagnosis can only be made histologically (Reddy et al., 2003; Morini et al., 2005; Smartt et al., 2005), but this is rarely done. In most published cases, the term 'anophthalmia' is used as a synonym for the more appropriate terms 'extreme microphthalmia' or 'clinical anophthalmia.'

Clinical features

Cecchetto (1920) reported a pedigree in which 2 brothers, each married to a first cousin, had a child with bilateral clinical anophthalmia. The common grandparents were also first cousins. Hesselberg (1951) reported affected children from first-cousin parents. Sorsby (1934) discovered early reports of affected sibs with normal parents. Ashley (1947) reported an affected Japanese brother and sister.

Warburg (1993) gave a comprehensive phenotypic and etiologic classification of microphthalmos and ocular coloboma. She included the description of a consanguineous Arab family showing that the phenotype in autosomal recessive microphthalmos may include congenital cystic eye, anophthalmos, microphthalmos, or coloboma. Some affected family members were mentally retarded, while others were mentally healthy.

Gill and Harris (1959) reported a family in which the proband and her great-aunt had microphthalmos. Wolff (1930) described a family of 10 children whose parents were first cousins and among whom 3 males and 2 females had microphthalmos, high-grade hyperopia (up to +20d), and glaucoma. Holst (1952) observed 6 cases in 2 rela...

Symptoms

HEENT: Microphthalmos; Anophthalmos; Nanophthalmos; High-grade hyperopia; Glaucoma

Inheritance: Autosomal recessive; also dominant forms


Retrieved: 27-07-2015
Source: OMIM (original)
Associated genes: prdm5

Clinical features

A number sign (#) is used with this entry because of evidence that brittle cornea syndrome-2 (BCS2) is caused by homozygous mutation in the PRDM5 gene (614161) on chromosome 4q27.

For a general phenotypic description and discussion of genetic heterogeneity of brittle cornea syndrome, see BCS1 (229200).Cameron (1993) described 11 patients with blue sclerae, limbus-to-limbus corneal thinning, hypermobile joints, and consanguineous parents. Corneal rupture occurred in 7 patients (9 eyes) either spontaneously or following minimal trauma. Acute hydrops occurred in 3 patients. Bilateral microcornea was present in 1 patient, and 2 patients had unilateral increased corneal diameter due to secondary glaucoma after trauma. Peripheral sclerocornea was present bilaterally in 5 patients. Curvature abnormalities included cornea plana, keratoconus, and keratoglobus. Systemic abnormalities included increased skin laxity, pectus excavatum, scoliosis, congenital hip dislocation, recurrent shoulder dislocation, high-frequency hearing loss, high-arched palate, and mitral valve prolapse. Cameron (1993) stated that the term 'blue sclera' in this syndrome is a misnomer, as the sclera is more transparent and thinner than normal, revealing underlying uveal tissue; the blue appearance is most apparent in the region of the ciliary body, giving the appearance of a 'halo' at the limbus. In addition, photographic comparisons in patients followed for more than 5 years showed a less prominent blue appearance of the sclera with increasing age.

Burkitt Wright et al. (2011) reported a large consanguineous Pakistani family (designated 'BC-001') in which 4 sisters had corneal rupture after minor trauma. The affected sisters had high myopia, blue sclerae, keratoconus, keratoglobus, soft skin with easy bruising, hypermobility of the small joints, femoral epiph...

Symptoms

INHERITANCE: Autosomal recessive

HEAD AND NECK: [Ears]; Hearing loss, sensorineural and conductive; Hypercompliant tympanic membranes; [Eyes]; Blue sclerae; Corneal thinning; Corneal rupture; Myopia; Keratoconus; Keratoglobus; Megalocornea (in some patients); Sclerocornea (in some patients); Cornea plana (in some patients)

ABDOMEN: [External features]; Hernia, inguinal, umbilical, or epigastric (in some patients)

SKELETAL: Small joint hypermobility; Abnormal gait (in some patients); Increased fractures (in some patients); [Pelvis]; Developmental dysplasia of the hip (in some patients)

SKIN, NAILS, HAIR: [Skin]; Soft with easy bruising (in some patients); Poor healing with abnormal scarring (in some patients); Hyperelasticity (in some patients)

MUSCLE, SOFT TISSUE: Myalgia (in some patients)

MISCELLANEOUS: Heterozygous carriers have blue sclerae, small joint hypermobility, and mild thinning of cornea

MOLECULAR BASIS: Caused by mutation in the PR-domain containing protein-5 gene (PRDM5, 614161.0001)


Retrieved: 27-07-2015
Source: Orphanet (original)

Mietens syndrome is a very rare syndrome consisting of corneal opacity, nystagmus, strabismus, flexion contracture of the elbows with dislocation of the head of the radius and abnormally short ulnae and radii. To date, only nine cases have been reported. Ocular findings are striking. Dysmorphic features are not characteristic except for a small pinched nose and a depressed nasal root. Intellectual deficit and growth delay are observed in the majority of patients. An autosomal recessive pattern of inheritance is probable. Last update: July 2010


Retrieved: 27-07-2015
Source: OMIM (original)
Associated genes: hmx1

Clinical features

A number sign (#) is used with this entry because of evidence that oculoauricular syndrome (OCACS) is caused by homozygous mutation in the HMX1 gene (142992) on chromosome 4p16.Franceschetti and Valerio (1945) described a 3-year-old Swiss girl who had bilateral mild microphthalmia with marked corneal opacities similar to corneal sclerosis and increased intraocular pressure on the left, and whose vision was limited to perception of light. She also had bilateral symmetric abnormalities of the external ear, characterized by a primitive appearing intertragic notch and coloboma of the lobule. Her 6-year-old brother also had eye and ear malformations, including bilateral mild microphthalmia with microcornea, inferonasal coloboma of the iris, anteroinferior polar cataract, and microphakia. The fundus was not visible, and he could recognize objects at 30 cm. His ear findings were identical to his sister's; both sibs had normal hearing. Their mother had a bilateral mild symmetric abnormality of the ear lobes. The authors stated that there were no other anomalies in the patients or other family members.

Schorderet et al. (2008) reported a developmental defect affecting the eye and external ear in 3 members of a consanguineous Swiss family, 2 of whom had been described by Franceschetti and Valerio (1945). Their proband, the great-nephew of the previously described sibs, presented at 2 months of age with congenital nystagmus, bilateral microcornea, posterior synechiae, bilateral cataract, colobomatous microphthalmia of the right eye, and anterior segment dysgenesis consisting of incomplete coloboma of the iris, stromal iris cyst of the right eye, and iridocorneal adherences in the left eye. Fundal examination revealed dysplastic macropapillae reminiscent of morning glory syndrome (see 120430), macular hypoplasia, and peripheral inferonasal chorioretinal coloboma. The cataract was rapidly progressive, requiring surgery at 11 months of age. Ophthalmoscopy at 7 years of age revealed the presence of circumferential abnormalities of the retinal pigment epithelium and chorioretinal atrophic lacunae at the equator, and the patient had rod-cone dystrophy on electroretinogram (ERG). His ears showed lobular aplasia, a narrow intertragic notch, and an abnormal bridge connecting the crus of the helix and antihelix, resulting in complete separation between the cymba and the conqua. Audiogram and...

Symptoms

INHERITANCE: Autosomal recessive

HEAD AND NECK: [Ears]; Lobular aplasia; Narrow intertragic notch; Abnormal bridge connecting the crus of the helix and antihelix; [Eyes]; Nystagmus; Microphthalmia; Microcornea; Cataract; Coloboma; Chorioretinal atrophic lacunae; Morning glory-like dysplastic macropapillae; Macular hypoplasia; Microphakia; Rod-cone dystrophy; Sclerocornea; Increased intraocular pressure

MOLECULAR BASIS: Caused by mutation in the homeobox (H6 family) 1 gene (HMX1, 142992.0001)


Retrieved: 28-07-2015
Source: GeneReviews (original)

Summary

Summary Clinical characteristics

Microphthalmia, anophthalmia, and coloboma comprise the MAC spectrum of ocular malformations. Microphthalmia refers to a globe with a total axial length that is at least two standard deviations below the mean for age. Anophthalmia refers to complete absence of the globe in the presence of ocular adnexa (eyelids, conjunctiva, and lacrimal apparatus). Coloboma refers to the ocular malformations that result from failure of closure of the optic fissure. Chorioretinal coloboma refers to coloboma of the retina and choroid. Iris coloboma causes the iris to appear keyhole-shaped. Microphthalmia, anophthalmia, and coloboma may be unilateral or bilateral; when bilateral they may occur in any combination. Diagnosis/testing. Molecular genetic testing (which can include sequence analysis, gene-targeted deletion/duplication analysis, and chromosome microarray analysis [CMA]) can identify a genetic cause in 80% of individuals with bilateral anophthalmia/severe microphthalmia and in up to 20% of all individuals with an ocular malformation in the MAC spectrum. Management. Treatment of MAC spectrum: Prosthetic intervention is appropriate for those with severe microphthalmia and anophthalmia. In many infants, an ocularist can start shortly after birth to expand the palpebral fissures, conjunctival cul-de-sac, and orbit using conformers of progressively increasing size. An oculoplastic surgeon can help determine the most suitable options for surgical intervention after age six months (when postnatal growth of the orbit can be assessed) and before the age that orbital dimensions are fixed (after which extensive orbital reconstruction may be required). Children with reduced vision may benefit from visual aids and other visual resources as well as early intervention to help optimize psychomotor development, educational endeavors, life skills, and mobility. Protection of the healthy eye in those with unilateral involvement is recommended. Genetic counseling. When an inherited or de novo chromosome abnormality or a specific syndrome is identified either by phenotypic findings or by genetic/genomic testing, genetic counseling is indicated based on the mode of inheritance for that condition.

Clinical characteristics

Microphthalmia, anophthalmia, and coloboma comprise the MAC spectrum of ocular malformations. Microphthalmia refers to a globe with a total axial length that is at least two standard deviations below the mean for age. Anophthalmia refers to complete absence of the globe in the presence of ocular adnexa (eyelids, conjunctiva, and lacrimal apparatus). Coloboma refers to the ocular malformations that result from failure of closure of the optic fissure. Chorioretinal coloboma refers to coloboma of the retina and choroid. Iris coloboma causes the iris to appear keyhole-shaped. Microphthalmia, anophthalmia, and coloboma may be unilateral or bilateral; when bilateral they may occur in any combination.Micr...