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Arthrogryposis, distal, type 2e

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

Description

In 4 generations of a family, Hall et al. (1975) observed a syndrome of small mouth and jaw with limited jaw movement disappearing by adulthood but with horizontal depression above the chin; mild microcephaly; ears missing the antihelix; and severe flexion contractures of the hands and feet, leading to subluxation of the fingers and clubfeet in the most severely affected child. There was no male-to-male transmission.

Hall et al. (1982) reported 13 additional unrelated patients with a disorder similar to that described by Hall et al. (1975). They termed the disorder distal arthrogryposis type IIe. Clinical features in all patients included trismus and an unusual camptodactyly in the newborn period with hyperextension of the metacarpophalangeal joint, distal flexion contractures, and variations in the degree of severity. All patients also had hip and feet involvement, and wrists were commonly flexed. Other variable features included mild developmental delay, micrognathia, horizontal groove on the chin, facial asymmetry, reduced facial expression, and high-arched palate. The inheritance pattern in 3 families was consistent with autosomal dominance. Average paternal age at conception was 36.

This disorder shows phenotypic overlap with trismus-pseudocamptodactyly syndrome (158300).

Symptoms

Mouth: Small mouth; Small jaw; Limited jaw movement; Horizontal depression above the chin

Head: Mild microcephaly

Ears: Antihelix absent

Limbs: Severe flexion contractures of hands and feet; Subluxation of fingers; Clubfeet

Inheritance: Autosomal dominant
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Ehlers-danlos syndrome, autosomal dominant, type unspecified

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

Description

The large number of distinct types of the Ehlers-Danlos syndrome that have already been identified indicates great heterogeneity, but clearly that heterogeneity is not exhausted by the present classification. Some of the unclassified families are apparently recessive (see 225320); some, such as that reported by Friedman and Harrod (1982), are seemingly dominant. These authors reported a mother and son with large hernias, positional foot deformities, thoracic deformity, asthma, and eczematoid dermatitis. Both had facial asymmetry, prominent nasal bridge and small jaw. The mother had severe thoracolumbar kyphoscoliosis and 'cigarette paper' scars over the legs. She died of dissecting aortic aneurysm and at autopsy had cystic medial necrosis of the aorta and myxomatous degeneration and elongation of the mitral and tricuspid valves. McKusick (1972) observed dissecting aortic aneurysm in type VI EDS (225400). Loose-jointedness, stretchable skin, Gorlin sign (tip of tongue to tip of nose) and a few papyraceous scars occurred in a man who died of dissecting aneurysm, as did his sister and mother who showed similar systemic signs.

Symptoms

Abdomen: Hernias

Limbs: Positional foot deformities

Thorax: Thoracic deformity

Pulmonary: Asthma

Skin: Eczematoid dermatitis; Stretchable skin; Cigarette-paper scars

Facies: Facial asymmetry; Prominent nasal bridge; Small jaw; Gorlin sign (tip of tongue to tip of nose)

Spine: Thoracolumbar kyphoscoliosis

Joints: Loose-jointedness

Vascular: Dissecting aortic aneurysm

Lab: Cystic medial necrosis of the aorta; Myxomatous valvular degeneration

Inheritance: Autosomal dominant form(s); genetic heterogeneity
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Crumpled helices and small mouth

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

Clinical features

Bacha and Hoo (2001) described a brother and sister of a Bosnian refugee family with similar clinical features, including sparse hair in the first year of life, prominent nose, small mouth, micrognathia, high-arched palate or cleft palate, crumpled upper helices, flexion limitation of the distal interphalangeal joints of the fingers, and mild developmental delay. The authors suggested that this represented a distinct entity with autosomal recessive inheritance.
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Escher Hirt syndrome

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

Escher Hirt syndrome

Escher-Hirt syndrome is characterized by small ears with thickened ear lobes, a small jaw, and conductive hearing loss due to ear abnormalities. It has only been described in a few families. Escher-Hirt syndrome is inherited in an autosomal dominant pattern
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Hanhart syndrome

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

Hanhart syndrome

Hanhart syndrome is a rare condition that primarily affects the craniofacial region and the limbs (arms and legs). People affected by this condition are often born with a short, incompletely developed tongue; absent or partially missing fingers and/or toes; abnormalities of the arms and/or legs; and an extremely small jaw. The severity of these physical abnormalities varies greatly among affected people, and children with this condition often have some, but not all, of the symptoms. The cause of Hanhart syndrome is not fully understood. Treatment depends on the signs and symptoms present in each person
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Multiple pterygium syndrome

Retrieved: 27-07-2015
Source: GHR (Original article)
Associated genes: chrng, tpm2, gbe1

What is multiple pterygium syndrome?

Multiple pterygium syndrome is a condition that is evident before birth with webbing of the skin (pterygium) at the joints and a lack of muscle movement (akinesia) before birth. Akinesia frequently results in muscle weakness and joint deformities called contractures that restrict the movement of joints (arthrogryposis). As a result, multiple pterygium syndrome can lead to further problems with movement such as arms and legs that cannot fully extend. The two forms of multiple pterygium syndrome are differentiated by the severity of their symptoms. Multiple pterygium syndrome, Escobar type (sometimes referred to as Escobar syndrome) is the milder of the two types. Lethal multiple pterygium syndrome is fatal before birth or very soon after birth. In people with multiple pterygium syndrome, Escobar type, the webbing typically affects the skin of the neck, fingers, forearms, inner thighs, and backs of the knee. People with this type may also have arthrogryposis. A side-to-side curvature of the spine (scoliosis) is sometimes seen. Affected individuals may also have respiratory distress at birth due to underdeveloped lungs (lung hypoplasia). People with multiple pterygium syndrome, Escobar type usually have distinctive facial features including droopy eyelids (ptosis), outside corners of the eyes that point downward (downslanting palpebral fissures), skin folds covering the inner corner of the eyes (epicanthal folds), a small jaw, and low-set ears. Males with this condition can have undescended testes (cryptorchidism). This condition does not worsen after birth, and affected individuals typically do not have muscle weakness later in life. Lethal multiple pterygium syndrome has many of the same signs and symptoms as the Escobar type. In addition, affected fetuses may develop a buildup of excess fluid in the body (hydrops fetalis) or a fluid-filled sac typically found on the back of the neck (cystic hygroma). Indiv...

Keywords

multiple pterygium syndrome,Skin Diseases, Genetic,Genetic Diseases, Inborn,Skin Diseases,Skin and Connective Tissue Diseases,Congenital, Hereditary, and Neonatal Diseases and Abnormalities,Bones, muscles, and connective tissues,Skin, hair, and nails,arthrogryposis multiplex congenita,prenatal myasthenia,CHRNA1,CHRNA1 gene,CHRND,CHRND gene,CHRNG,CHRNG gene,RAPSN,RAPSN gene,Escobar syndrome,familial pterygium syndrome,pterygium 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,congenital,heritable disorders,inherited disorders
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Acrogeria, Gottron type

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

Acrogeria, Gottron type

Acrogeria, Gottron type is a premature aging syndrome. Characteristic signs include fragile, thin skin on the hands and feet. Other parts of the body (e.g., face, forearms, and lower legs) are variably affected. It is generally considered to be a mild, nonprogressive, congenital form of skin atrophy due to the loss of the fatty tissue directly under the skin. Other symptoms reported in individual cases include small hands and feet, prominent veins on the chest, small stature, small jaw, premature senility, premature hair greying, endocrine disturbances, and cataracts. Currently the cause of this condition is unknown
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Acrogeria

Retrieved: 27-07-2015
Source: WIKIPEDIA (Original article)
Acrogeria (also known as "Gottron's syndrome") is a cutaneous condition characterized by premature aging, more especially in the form of unusually fragile, thin skin on the hands and feet (distal extremities). The prefix "acro" stems from the Greek akros which alludes to "extremity, tip" while the suffix "geria" comes from the Greek gerôn which means "elder". This is one of the classic congenital premature aging syndromes, occurring early in life, among which are: pangeria (Werner's syndrome), progeria (Hutchinson-Gilford's syndrome) and acrogeria (Gottron's syndrome) and was characterized in 1940.Gottron, H. Familiaere Akrogerie. Arch. Derm. Syph. 181: 571-583, 1940. Onset is in early childhood, it progresses over the next few years and then remains stable over time with morphology, colour and site remaining constant. A bruising tendency has been observed. It is believed that Gottron syndrome may affect more females than males. Approximately forty cases have been reported in the medical literature, since the discovery of the disorder.

Signs and symptoms

This disorder is characterized by a reduction and loss of subcutaneous fat and collagen of the hands and feet, above all. It can be defined it as a mild, nonprogressive, congenital form of premature skin senility due to the disappearance of the fatty tissue directly under the skin. More precisely, skin lesions deal with large, fixed, geographic and symmetrical fine scaly recessive erythematous plaques distributed over the dorsal side of distal extremities. Skin lesions can be associated with osteoarticular alterations. Other outcomes and observations may include abnormally small hands and feet with unusually prominent veins on the upper trunk (chest), short stature, and, sometimes, abnormally small jaw (micrognathia). Most of the cases analyzed show atrophy of the skin at the tip of the nose, which gives a sculptural appearance. The nails may be dystrophic or thick, but, most of the time, they are normal. In the skin histopathology, there is atrophy of the dermis and subcutaneum. The collagen fibers are loose and dispersed, and the elastic fibers are always fragmented. However, the epidermis is not affected. Although some patients present clinical features similar to those of progeria and metageria, they do not usually show generalized atherosclerosis. Therefore, they do not usually have premature myocardic or coronary disease.

Causes

The etiology of acrogeria is still not well determined. This disorder is thought to be inherited as an autosomal recessive genetic trait. However, the mode of genetic inheritance is not accurately known. It has been considered autosomal dominant and autosomal recessive, though most reported cases own a positive family background. Mutations in the COL3A1 gene, located at chromosome 2q31–q32, have been reported in varied phenotypes, including acrogeria and vascular rupture in Ehlers-Danlos' syndrome (more especially type IV).

In the fibroblast culture, a reduction o...
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Ehlers-Danlos syndrome, progeroid type

Retrieved: 27-07-2015
Source: Orphanet (Original article)
Associated genes: b4galt7, dcn, prg2, tgfb1

Ehlers-Danlos syndrome, progeroid type (EDS-PF) is a form of Ehlers-Danlos syndrome (EDS; see this term) characterized by a premature aging with sparse hair, macrocephaly, loose elastic skin, failure to thrive, joint laxity, psychomotor retardation, hypotonia, and defective wound healing with atrophic scars. Last update: January 2014
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Ehlers-danlos syndrome, progeroid type, 1

Retrieved: 27-07-2015
Source: OMIM (Original article)
Associated genes: b4galt7, dcn, prg2, tgfb1

Description

A number sign (#) is used with this entry because Ehlers-Danlos syndrome progeroid type 1 (EDSP1) is caused by homozygous or compound heterozygous mutation in the B4GALT7 gene (604327) on chromosome 5q35.The features of the progeroid form of Ehlers-Danlos syndrome include an aged appearance, developmental delay, short stature, craniofacial disproportion, generalized osteopenia, defective wound healing, hypermobile joints, hypotonic muscles, and loose but elastic skin (Okajima et al., 1999).

- Genetic Heterogeneity of the Progeroid Type of Ehlers-Danlos Syndrome

See EDSP2 (615349), caused by mutation in the B3GALT6 gene (615349).

Clinical features

Kresse et al. (1987) described a boy, aged 4 years 9 months, with features of both Ehlers-Danlos syndrome and progeria. In addition to delayed mental development, there were multiple abnormalities of connective tissue, including short stature, osteopenia of all bones and dysplasia of some, defective deciduous teeth, loose but elastic skin, delayed wound healing with the formation of thin, atrophic scars, scanty scalp hair, hypotonic muscles, and hypermobile joints. The patient lacked several characteristic features of progeria (176670) such as diminished subcutaneous fat, prominent scalp veins, generalized alopecia, and joint contractures. He also did not conform with well-defined progeroid syndromes since he lacked the severe mental deficiency and neurologic abnormalities of de Barsy syndrome (219150), the deafness and photosensitivity of Cockayne syndrome (216400), and the ocular abnormalities of Hallermann-Streiff syndrome (234100).

Hernandez et al. (1979) likewise reported cases (2 unrelated males) with what appeared to be a new variety of EDS. Mental retardation, short stature, wrinkled facies, curly and fine hair, scanty eyebrows and eyelashes, te...

Symptoms

INHERITANCE: Autosomal recessive

GROWTH: [Height]; Short stature; [Other]; Failure to thrive

HEAD AND NECK: [Head]; Macrocephaly; [Face]; Broad, flat forehead; Small face; [Ears]; Absent ear lobes; [Eyes]; Prominent eyes; [Nose]; Broad nasal bridge; [Mouth]; Small mouth; Bifid uvula

CHEST: [External features]; Narrow chest; [Ribs, sternum, clavicles, and scapulae]; Short clavicles

SKELETAL: Osteopenia; [Pelvis]; Coxa valga; [Limbs]; Joint laxity; Radioulnar synostosis; [Hands]; Transverse palmar creases; Long, slender fingers; [Feet]; Long, slender toes; Pes planus

SKIN, NAILS, HAIR: [Skin]; Loose, elastic skin; Thin, atrophic scars; Transverse palmar creases; Cutis gyrata of palms and soles; [Hair]; Sparse scalp hair

NEUROLOGIC: [Central nervous system]; Psychomotor retardation; Hypotonia

LABORATORY ABNORMALITIES: Galactosyltransferase I deficiency in fibroblasts

MOLECULAR BASIS: Caused by mutations in the xylosylprotein 4-beta-galactosyltransferase, polypeptide 7 gene (B4GALT7, 604327.0001)
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Raine syndrome

Retrieved: 27-07-2015
Source: OMIM (Original article)
Associated genes: fam20c

Description

A number sign (#) is used with this entry because of evidence that Raine syndrome is caused by homozygous or compound heterozygous mutation in the FAM20C gene (611061) on chromosome 7p22.Raine syndrome is a neonatal osteosclerotic bone dysplasia of early and aggressive onset that usually results in death within the first few weeks of life, although there have been some reports of survival into childhood. Radiographic studies show a generalized increase in the density of all bones and a marked increase in the ossification of the skull. The increased ossification of the basal structures of the skull and facial bones underlies the characteristic facial features, which include narrow prominent forehead, proptosis, depressed nasal bridge, and midface hypoplasia. Periosteal bone formation is also characteristic of this disorder and differentiates it from osteopetrosis and other known lethal and nonlethal osteosclerotic bone dysplasias. The periosteal bone formation typica...

Symptoms

INHERITANCE: Autosomal recessive

GROWTH: [Height]; Short stature

HEAD AND NECK: [Head]; Microcephaly; Brachycephaly; Turribrachycephaly; Plagiocephaly (in some patients); Wide fontanelles; [Face]; Craniofacial dysplasia; Midface hypoplasia; 'Fishlike' facies; Choanal atresia or choanal stenosis; Micrognathia; Prognathism (in some patients); [Ears]; Low-set ears; Dysplastic ears (in some patients); Posteriorly rotated ears (in some patients); Protruding ears (in some patients); Hearing loss, mixed (in some patients); [Eyes]; Exophthalmos; Downslanting palpebral fissures; Hypertelorism (in some patients); Arched eyebrows (in some patients); [Nose]; Hypoplastic nose; Depressed nasal bridge; [Mouth]; Gingival hyperplasia; Cleft palate; High palate; Small mouth; Wide mouth (in some patients); Large protruding tongue; [Teeth]; Abnormal teeth (in some patients); Natal teeth (in some patients); Small teeth (in some patients); Enamel dysplasia (in some patients); [Neck]; Short neck

RESPIRATORY: [Lung]; Pulmonary hypoplasia

CHEST: [External features]; Pectus excavatum (in some patients); Small thorax; [Ribs, sternum, clavicles, and scapulae]; Multiple fracture-like rib lesions

GENITOURINARY: [External genitalia, male]; Microscrotum (in some patients); [Kidneys]; Decreased tubular resorption of phosphate (in some patients); Hydronephrosis (in some patients); Double renal pelvis (in some patients); Renal cortex calcification (in some patients); [Ureters]; Hydroureter, bilateral (in some patients); Stenotic ostia of ureters (in some patients)

SKELETAL: Osteosclerosis, generalized; Arthrogryposis (rare); [Spine]; Absence of ossification of vertebral bodies C3 to C5 (rare); Vertebral segmentation defects (rare); [Skull]; Osteosc...
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Arthrogryposis, distal, type 1a

Retrieved: 27-07-2015
Source: OMIM (Original article)
Associated genes: tpm2, myh3, tnnt3

Description

A number sign (#) is used with this entry because distal arthrogryposis type 1A (DA1A) is caused by heterozygous mutation in the TPM2 gene (190990) on chromosome 9p13.The distal arthrogryposes are a group of disorders that mainly involve the distal parts of the limbs. They are characterized by congenital contractures of 2 or more different body areas without a primary neurologic or muscle disease. The prototypic distal arthrogryposis is type 1 (DA1), which is characterized largely by camptodactyly and clubfoot. Hypoplasia and/or absence of some interphalangeal creases is common. The shoulders and hips are less frequently affected. While the pattern of affected joints is consistent, the degree to which the joints are affected is highly variable, with equinovarus deformities ranging from mild to severe and hand involvement ranging from isolated hypoplasia of the distal interphalangeal crease of the fifth digit to severely clenched fists and ulnar deviation of the wrist. The various phenotypic forms of distal arthrogryposis are classified hierarchically according to the proportion of features they share with one another and are designated DA1 through DA10 (summary by Bamshad et al., 2009).

There are other forms of arthrogryposis multiplex congenita (AMC), including a lethal congenital form (see LCCS1, 253310).

- Genetic Heterogeneity of Distal Arthrogryposes

Distal arthrogryposis type 1 includes DA1A, caused by mutation in the TPM2 gene, and DA1B (614335), caused by mutation in the MYBPC1 gene (160794) on chromosome 12q23.2. Other forms include DA2A (Freeman-Sheldon syndrome, 193700), caused by mutation in the MYH3 gene (160720) on chromosome 17p13.1; DA2B (Sheldon-Hall syndrome, 601680), caused by mutation in MYH3, the TNNT3 gene (600692) on chromosome 11p15.5, the TNNI2 gene (191043), also on 11p15.5, or TPM2 (190990) on chromosome 9p13; DA3 (Gordon syndrome, 114300) and DA5 (108145), caused by mutation in...

Symptoms

INHERITANCE: Autosomal dominant

CHEST: [Ribs, sternum, clavicles, and scapulae]; Stiff shoulders

SKELETAL: [Spine]; Mild scoliosis; [Pelvis]; Hip flexion contractures; Congenital hip dislocations; Decreased hip abduction; [Limbs]; Elbow flexion contractures; Knee flexion contractures; [Hands]; Tightly clenched fists (neonate); Camptodactyly (adult); Ulnar deviation (adult); Absent distal interphalangeal creases; Single transverse palmar creases; [Feet]; Talipes equinovarus; Calcaneovalgus deformities; Vertical talus

SKIN, NAILS, HAIR: [Skin]; Absent distal interphalangeal creases; Single transverse palmar creases

NEUROLOGIC: [Central nervous system]; Normal intelligence

MISCELLANEOUS: Marked intrafamilial and interfamilial variability; Most frequently affected joints - hands (98%) and feet (88%); Genetic heterogeneity (see 601680)

MOLECULAR BASIS: Caused by mutations in the tropomyosin 2 gene (TPM2, 190990.0001)
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Fetal akinesia deformation sequence

Retrieved: 27-07-2015
Source: OMIM (Original article)
Associated genes: chrng, rapsn, dok7, gbe1

Description

A number sign (#) is used with this entry because biallelic mutations in the RAPSN (601592), DOK7 (610285), and MUSK (601296) genes have been identified in patients with a fetal akinesia deformation sequence (FADS) phenotype.

As mutations in these genes have been associated with congenital myasthenic syndromes (see, e.g., CMS1A; 601462), the disorders in these patients likely represent extreme phenotypes of CMS (Vogt et al., 2009).The fetal akinesia deformation sequence (FADS) refers to a clinically and genetically heterogeneous constellation of features including fetal akinesia, intrauterine growth retardation, arthrogryposis, and developmental anomalies, including lung hypoplasia, cleft palate, and cryptorchidism (Vogt et al., 2009). It shows phenotypic overlap with the lethal form of multiple pterygium syndrome (see 253290).

Nomenclature

Although early descriptions by Pena and Shokeir (1974, 1976) resulted in the eponym, Moessinger (1983), Hall (1986), and Hageman et al. (1987) noted that Pena-Shokeir is not a specific unitary diagnosis or syndrome, but rather a description of a clinically and genetically heterogeneous phenotype resulting from fetal ak...

Symptoms

INHERITANCE: Autosomal recessive

GROWTH: [Other]; Small for gestational age; Intrauterine growth retardation

HEAD AND NECK: [Face]; Rigid, expressionless face; Long philtrum; Micrognathia; [Ears]; Small, posteriorly rotated ears; Poorly folded ears; [Eyes]; Prominent eyes; Hypertelorism; Telecanthus; Short palpebral fissures; Ptosis; [Nose]; Depressed nasal tip; [Mouth]; Small mouth; High arched palate; Cleft palate; [Neck]; Short neck

RESPIRATORY: [Lung]; Pulmonary hypoplasia

CHEST: [External features]; Small thorax; [Ribs, sternum, clavicles, and scapulae]; Thin ribs

ABDOMEN: [Gastrointestinal]; Short-gut syndrome

GENITOURINARY: [Internal genitalia, male]; Cryptorchidism

SKELETAL: [Pelvis]; Hip ankylosis; [Limbs]; Elbow ankylosis; Knee ankylosis; Thin, gracile long bones; [Hands]; Ulnar deviation of hands; Camptodactyly; Absent or sparse dermal ridges; [Feet]; Ankle ankylosis; Rocker-bottom feet; Talipes equinovarus

MUSCLE, SOFT TISSUE: Neurogenic muscle atrophy

NEUROLOGIC: [Central nervous system]; Hydrocephalus; Microgyria; Cerebellar hypoplasia; Absent septum pellucidum; Cavum septum pellucidum

PRENATAL MANIFESTATIONS: [Amniotic fluid]; Polyhydramnios; [Placenta and umbilical cord]; Small or abnormal placenta; Short umbilical cord; [Delivery]; Premature birth; Stillborn (30%)

MOLECULAR BASIS: Caused by mutation in the 43-kD receptor-association protein of the synapse, gene (RAPSN, 601592.0013); Caused by mutation in the downstream of tyrosine kinase 7 gene (DOK7, 610285.0009); Caused by mutation in the skeletal muscle receptor tyrosine kinase gene (MUSK, 601296.0006)
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Oral and digital anomalies with ichthyosis

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

Description

In a male and female offspring of healthy first-cousin Pakistani parents, Clayton-Smith and Donnai (1989) described a similar pattern of unusual facial features, limb malformations, and postnatal-onset ichthyosis. The male had a small mouth with thin upper lip and a midline groove in the lower lip. In both children the fingers were tapering and lacked distal flexion creases. The daughter had a large gap between the second and third fingers.

Symptoms

Skin: Postnatal-onset ichthyosis

HEENT: Small mouth; Thin upper lip; Midline groove in lower lip

Limbs: Tapered fingers; Distal finger flexion creases absent; Gap between second and third fingers

Inheritance: Autosomal recessive
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Ichthyosis - oral and digital anomalies

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

This syndrome is characterised by ichthyosis, unusual facies (small mouth with a thin upper lip and lower lip with a midline groove) and digital anomalies (tapered fingers with a lack of distal flexion creases and wide spacing between the second and third fingers). It has been described in two sibs born to first cousin parents. Transmission appears to be autosomal recessive. Last update: April 2007
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Treacher Collins syndrome

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

Treacher Collins syndrome

Treacher Collins syndrome (TCS) is a condition that affects the development of bones and other tissues in the face. The signs and symptoms of this disorder vary greatly, ranging from almost unnoticeable to severe. Most affected people have underdeveloped facial bones, particularly the cheek bones, and a very small jaw and chin (micrognathia). Other features may include cleft palate, eye abnormalities, and hearing loss. TCS may be caused by mutations in the TCOF1, POLR1C, or POLR1D genes. When it is due to the TCOF1 or POLR1D gene, it is inherited in an autosomal dominant manner. About 60% of these cases are due to a new mutation in the gene and are not inherited from a parent. When it is due to the POLR1C gene, it is inherited in an autosomal recessive manner. In some cases, the genetic cause of the condition is unknown
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Treacher Collins syndrome

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

What is Treacher Collins syndrome?

Treacher Collins syndrome is a condition that affects the development of bones and other tissues of the face. The signs and symptoms of this disorder vary greatly, ranging from almost unnoticeable to severe. Most affected individuals have underdeveloped facial bones, particularly the cheek bones, and a very small jaw and chin (micrognathia). Some people with this condition are also born with an opening in the roof of the mouth called a cleft palate. In severe cases, underdevelopment of the facial bones may restrict an affected infant's airway, causing potentially life-threatening respiratory problems. People with Treacher Collins syndrome often have eyes that slant downward, sparse eyelashes, and a notch in the lower eyelids called an eyelid coloboma. Some affected individuals have additional eye abnormalities that can lead to vision loss. This condition is also characterized by absent, small, or unusually formed ears. Hearing loss occurs in about half of all affected individuals; hearing loss is caused by defects of the three small bones in the middle ear, which transmit sound, or by underdevelopment of the ear canal. People with Treacher Collins syndrome usually have normal intelligence.

How common is Treacher Collins syndrome?

This condition affects an estimated 1 in 50,000 people.

What genes are related to Treacher Collins syndrome?

Mutations in the TCOF1, POLR1C, or POLR1D gene can cause Treacher Collins syndrome. TCOF1 gene mutations are the most common cause of the disorder, accounting for 81 to 93 percent of all cases. POLR1C and POLR1D gene mutations cause an additional 2 percent of cases. In individuals without an identified mutation in one of these genes, the genetic cause of the condition is unknown. The proteins produced from the TCOF1, POLR1C, and POLR1D genes all appear to play important roles in the early development of bones and other tissues of the face. These proteins are involved in the production of a molecule called ribosomal RNA (rRNA), a chemical cousin of DN...

Keywords

Treacher Collins syndrome,Bone Diseases,Congenital Abnormalities,Craniofacial Abnormalities,Dysostoses,Congenital, Hereditary, and Neonatal Diseases and Abnormalities,Musculoskeletal Diseases,Bone Diseases, Developmental,Craniofacial Dysostosis,Musculoskeletal Abnormalities,Mandibulofacial Dysostosis,Bones, muscles, and connective tissues,Mouth and teeth,Ear, nose, and throat,Eyes and vision,branchial arches,neural crest cells,treacle,POLR1C,POLR1C gene,POLR1D,POLR1D gene,TCOF1,TCOF1 gene,Franceschetti-Zwahlen-Klein syndrome,mandibulofacial dysostosis (MFD1),Treacher Collins-Franceschetti syndrome,zygoauromandibular dysplasia,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
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Growth delay - hydrocephaly - lung hypoplasia

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

Growth delay - hydrocephaly - lung hypoplasia, also named Game-Friedman-Paradice syndrome, is a rare developmental disorder described in 4 sibs so far and characterized by delayed fetal growth, hydrocephaly with patent aqueduct of Sylvius, underdeveloped lungs and various other anomalies such as small jaw, intestinal malrotation, omphalocele, shortness of lower limbs, bowed tibias and foot deformities. Last update: February 2012
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Sonoda syndrome

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

Clinical features

Among the children of presumably unrelated parents who, however, came from lines that had been located in a rather small town for a long time, Sonoda et al. (1988) described 2 boys and a girl with a syndrome of congenital heart disease, round face with depressed nasal bridge, small mouth, short stature, developmental retardation, relatively dark skin, and high axial triradius in the dermatoglyphic analysis. Pulmonary valvular stenosis was diagnosed in 1 of the children; in a second, ventricular septal defect, which was thought to have closed spontaneously, was diagnosed, and the same lesion may have been present in the third child.

Symptoms

Cardiac: Congenital heart defect; Pulmonary valvular stenosis; Ventricular septal defect

HEENT: Round face; Depressed nasal bridge; Small mouth

Growth: Short stature

Neuro: Mental retardation,

Skin: Dark skin; High axial triradius

Inheritance: Autosomal recessive
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Heart defect - round face - congenital developmental delay

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

Heart defect – round face – congenital developmental delay is very rare syndrome described in three sibs of one Japanese family and characterized by congenital heart disease, round face with depressed nasal bridge, small mouth, short stature, and relatively dark skin and typical dermatoglyphic anomalies, and intellectual deficit. Last update: February 2012
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Microstomia

Retrieved: 27-07-2015
Source: WIKIPEDIA (Original article)
Microstomia (micro- a combining form meaning small + -stomia a combining form meaning mouth = (abnormally) "small mouth") is a clinical feature of many craniofacial syndromes, including Freeman-Sheldon syndrome and Sheldon-Hall syndromes (or distal arthrogryposis multiplex congenita). It may present with whistling-face feature, as well, as in Freeman-Sheldon syndrome. In this syndrome, it impairs alimentation and may require repeated oral surgeries (called commissurotomy) to improve function. It can also be a feature of systemic scleroderma.
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Ehlers-Danlos syndrome, musculocontractural type

Retrieved: 27-07-2015
Source: Orphanet (Original article)
Associated genes: chst14

Ehlers-Danlos syndrome, musculocontractural type (MCEDS) is a form of Ehlers-Danlos syndrome (EDS; see this term) characterized by distinct craniofacial features, multiple contractures, progressive joint and skin laxity, adducted thumb, talipes equinovarus, hemorrhagic diathesis and multisystem fragility-related manifestations. Last update: January 2014
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Ehlers-danlos syndrome, musculocontractural type 1

Retrieved: 27-07-2015
Source: OMIM (Original article)
Associated genes: chst14

Description

A number sign (#) is used with this entry because of evidence that Ehlers-Danlos syndrome musculocontractural type 1 (EDSMC1) is caused by homozygous or compound heterozygous mutation in the CHST14 gene (608429) on chromosome 15q14.The Ehlers-Danlos syndromes (EDS) are a group of heritable connective tissue disorders that share the common features of skin hyperextensibility, articular hypermobility, and tissue fragility (Beighton et al., 1998).

The major characteristics of the musculocontractural form of EDS include distinctive craniofacial dysmorphism, congenital contractures of thumbs and fingers, clubfeet, severe kyphoscoliosis, muscular hypotonia, hyperextensible thin skin with easy bruisability and atrophic scarring, wrinkled palms, joint hypermobility, and ocular involvement (summary by Malfait et al., 2010).

- Genetic Heterogeneity of Musculocontractural Ehlers-Danlos Syndrome

Ehlers-Danlos syndrome musculocontractural type 2 (EDSMC2; 615539...

Symptoms

INHERITANCE: Autosomal recessive

GROWTH: [Weight]; Severely wasted build

HEAD AND NECK: [Head]; Brachycephaly; Large fontanel with delayed closure; [Face]; Broad, flat forehead; Microretrognathia in infancy; Protruding jaw from adolescence; Facial asymmetry from adolescence; [Ears]; Low-set and rotated ears; Prominent ears; Hearing impairment; [Eyes]; Eye anomalies, variable; Blue sclerae; Hypertelorism; Downslanting palpebral fissures; Strabismus; Myopia; Glaucoma; Microcornea; Retinal detachment; Anterior chamber abnormality; [Nose]; Short with hypoplastic columella; Long philtrum; [Mouth]; Thin upper lip; Small mouth in infancy; High-arched palate; Cleft palate

CARDIOVASCULAR: [Heart]; Valve anomalies; Atrial septal defect; [Vascular]; Hematomas, recurrent large subcutaneous

RESPIRATORY: [Lung]; Hemopneumothorax

CHEST: [Ribs, sternum, clavicles, and scapulae]; Pectus excavatum; Flat, thin pectus; [Diaphragm]; Hiatal hernia

ABDOMEN: [External features]; Umbilical hernia; Diastasis recti; [Gastrointestinal]; Constipation; Diverticular perforation (rare); Duodenal obstruction due to malrotation

GENITOURINARY: [Internal genitalia, male]; Cryptorchidism (in most patients); [Kidneys]; Hydronephrosis, bilateral; [Bladder]; Cystitis, recurrent (in some patients); Enlarged bladder (in some patients)

SKELETAL: Mild osteopenia in childhood (in some patients); Congenital contractures, multiple; Joint laxity, generalized; Joint dislocations, recurrent; Tendon abnormalities; [Spine]; Scoliosis; [Limbs]; Hypermobility of shoulders; [Hands]; Adducted thumbs, bilateral, in infancy; Arachnodactyly; Slender and/or cylindrical fingers; Arthrogryposis, distal; Hypermobility of small joints; [Feet...
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Hunter-McAlpine craniosynostosis

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

This syndrome is characterised by craniosynostosis, intellectual deficit, short stature, facial dysmorphism (oval face with almond-shaped palpebral fissures, droopy eyelids and a small nose) and minor distal anomalies. It has been described in 10 patients. Transmission is autosomal dominant and the syndrome is associated with partial duplication of the long arm of chromosome 5 (5q35-5qter). Last update: September 2007
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Hunter-mcalpine craniosynostosis syndrome

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

Clinical features

Hunter et al. (1977) identified 6 members of family with characteristic facial features, including microcephaly, almond-shaped palpebral fissures, and downturned or small mouth, mental retardation, mild skeletal anomalies, short stature, and craniosynostosis.

Van Maldergem et al. (1990) and Ades et al. (1993) reported 3 additional patients with similar features.

Thomas et al. (1996) reported a patient and suggested the designation Hunter-McAlpine syndrome for this disorder. There is phenotypic overlap with Ruvalcaba syndrome (180870).

Cytogenetics

Thomas et al. (1996) described a sporadic case who also had an interstitial deletion of 17q23.1-q24.2, suggesting the possibility that Hunter-McAlpine syndrome maps to that region.

In affected individuals of the family described by Hunter et al. (1977) and in the patient described by Ades et al. (1993), Hunter et al. (2005) identified cryptic translocations resulting in duplication of 5q35-qter. Subtelomeric FISH analysis in the family reported by Hunter et al. (1977) revealed the presence of 5qter material on the short arm of chromosome 13; all obligate carriers had the balanced translocation t(5;13). The patient reported by Ades et al. (1993) had an extra 5q signal present on 1q, indicating a duplication of 5qter and monosomy of 1qter. Hunter et al. (2005) noted similarities in clinical features between these cases and other reported cases with duplication of this chromosome segment.

Inheritance

The pedigree pattern in the family reported by Hunter et al. (1977) supported autosomal dominant inheritance.

Symptoms

Head: Craniosynostosis

Neuro: Mental deficiency

Eyes: Almond-shaped palpebral fissures

Mouth: Downturned or small mouth

Skel: Mild acral-skeletal anomalies

Growth: Short stature

Lab: 17q23.1-q24.2 deletion in a sporadic case

Inheritance: Autosomal dominant
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Teebi-shaltout syndrome

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

Description

Teebi and Shaltout (1989) described a syndrome of craniofacial anomalies, abnormal hair, camptodactyly, and caudal appendage in the daughter of consanguineous Arab parents. Craniofacial anomalies included scaphocephaly with prominent occiput and bitemporal depression, hypertelorism, ptosis and blepharophimosis, bulbous nose with hypoplastic alae nasi, small mouth, and abnormal teeth. Froster et al. (1993) reported on a second family with the same pattern of anomalies occurring in a liveborn female and 3 spontaneously aborted fetuses. Additional findings in their cases included unilateral microphthalmia and kidney anomalies. The parents were first cousins of Tunisian descent.
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Progeroid facial appearance with hand anomalies

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

Clinical features

Giannotti et al. (1997) described a father and son with a progeroid syndrome characterized by an unusual facial appearance, sparse subcutaneous fat, and hand anomalies including syndactyly, camptodactyly, and clinodactyly ('finger deviation'). Mild mental retardation, microcephaly, and congenital heart defect were found only in the son. The heart defect in the son was tetralogy of Fallot, which was corrected at the age of 4 years. At the age of 7, he showed sparse hair, prominent veins (particularly over the scalp and limbs), frontal bossing, upslanting palpebral fissures, bilateral blepharophimosis, prominent nose, short philtrum, small mouth, thin lips, rounded chin, and large, prominent, abnormally modeled ears, with folded helix, and prominent antehelix and antitragus. The fingers were long with partial cutaneous syndactyly of fingers 2 and 3 and clinocamptodactyly of the fifth fingers. Audiometric examination showed bilateral conductive deafness. The father was the first child of healthy, nonconsanguineous parents; his father was 33 and mother 28 years of age at the time of his birth. At the time of evaluation he was 48 years old. His facial anomalies were said to be superimposable to those found in his son, including blepharophimosis, prominent thin nose, short philtrum, small mouth, thin lips, and long prominent ears. There was radial deviation of the third fingers, ulnar deviation of the fourth fingers, and camptodactyly of the fifth fingers. Subcutaneous fat was sparse and a reticular venous pattern was prominent.

Symptoms

INHERITANCE: Autosomal dominant

HEAD AND NECK: [Head]; Microcephaly; [Face]; Short philtrum; Frontal bossing; [Ears]; Prominent ears; Conductive hearing loss; [Eyes]; Blepharophimosis; Upslanting palpebral fissures; [Nose]; Prominent nose; [Mouth]; Thin lips; Small mouth

CARDIOVASCULAR: [Heart]; Tetralogy of Fallot

SKELETAL: [Hands]; Long fingers; Partial cutaneous syndactyly (2-3 fingers); Fifth finger camptodactyly; Fifth finger clinodactyly

SKIN, NAILS, HAIR: [Skin]; Prominent veins (especially over scalp and limbs); [Hair]; Sparse hair

MUSCLE, SOFT TISSUE: Sparse subcutaneous fat

NEUROLOGIC: [Central nervous system]; Mental retardation, mild

PRENATAL MANIFESTATIONS: [Amniotic fluid]; Oligohydramnios
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Midface hypoplasia, obesity, developmental delay, and neonatal hypotonia

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

Description

Rozendaal et al. (2003) reported 2 brothers born to consanguineous parents who presented with hypotonia and hypoglycemia in the neonatal period and later developed obesity and developmental delay. They had brachydactyly and similar facial features, including a prominent forehead, low nasal bridge, midface hypoplasia, full lips, a small mouth, and small, low-set ears with overfolded helices. Their sister had mild developmental delay and obesity. No additional anomalies were found, and metabolic investigations, including peroxisomal functions, were normal. The authors suggested that the patients had a previously unreported condition with an autosomal recessive or X-linked mode of inheritance.

Symptoms

INHERITANCE: Autosomal recessive

GROWTH: [Weight]; Obesity

HEAD AND NECK: [Face]; Prominent forehead; Midface hypoplasia; [Ears]; Small ears; Low-set ears; Over-folded helices; Mixed hearing loss; Thick helices; [Eyes]; Broad lateral eyebrows; Epicanthal folds; Ptosis; [Nose]; Low nasal bridge; Anteverted nares; [Mouth]; Full lips; Small mouth

SKELETAL: Delayed bone age; [Hands]; Brachydactyly

SKIN, NAILS, HAIR: [Hair]; Coarse scalp hair; Broad lateral eyebrows

NEUROLOGIC: [Central nervous system]; Hypotonia (neonatal); Developmental delay

METABOLIC FEATURES: Hypoglycemia (neonatal)

MISCELLANEOUS: Sister of affected male siblings had mild learning disabilities and obesity
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Amelia (birth defect)

Retrieved: 27-07-2015
Source: WIKIPEDIA (Original article)
Amelia (birth defect) Amelia (from Greek ἀ- "lack of" plus μέλος (plural: μέλεα or μέλη) "limb") is the birth defect of lacking one or more limbs. It can also result in a shrunken or deformed limb. For example, a child might be born without an elbow or forearm. The term may be modified to indicate the number of legs or arms missing at birth, such as tetra-amelia for the absence of all four limbs. A related term is meromelia, which is the partial absence of a limb or limbs. http://www.healthline.com/galecontent/amelia?print=true

Causes

The complete absence of an arm or leg in amelia occurs as a result of the limb formation process being either prevented or interrupted very early in the developing embryo: between 24 and 36 days following fertilization.http://www.healthline.com/galecontent/amelia?print=true Tetra-amelia syndrome appears to have an autosomal recessive pattern of inheritance - that is, the parents of an individual with tetra-amelia syndrome each carry one copy of the mutated gene, but do not show signs and symptoms of the condition.http://ghr.nlm.nih.gov/condition/tetra-amelia-syndrome In a few cases, amelia may be attributed to health complications during the early stages of pregnancy, including infection, failed abortion or complications associated with removal of an IUD after pregnancy.

Description

Amelia may be present as an isolated defect, but it is often associated with major malformations in other organ systems. These frequently include cleft lip and/or palate, body wall defects, malformed head, and defects of the neural tube, kidneys, and diaphragm. Facial clefts may be accompanied by other facial anomalies such as abnormally small jaw, and missing ears or nose. The body wall defects allow internal organs to protrude through the abdomen. Head malformations may be minor to severe with a near absence of the brain. The diaphragm may be herniated or absent and one or both kidneys may be small or absent. or missing limbs

Symptoms

The diagnosis of tetra-amelia syndrome is established clinically and can be made on routine prenatal ultrasonography. WNT3 is the only gene known to be associated with tetra-amelia syndrome. Molecular genetic testing on a clinical basis can be used to diagnose the incidence of the syndrome. The mutation detection frequency is unknown as only a limited number of families have been studied. Affected infants are often stillborn or die shortly after birth.http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=tetra-amelia

See also

Amniotic Band Syndrome Dysmelia Hemimelia Phocomelia Tetra-colon Thalidomide
Ehlers–Danlos syndrome (EDS) is an inherited connective tissue disorder with different presentations that have been classified into several primary types. EDS is caused by a defect in the structure, production, or processing of collagen or proteins that interact with collagen, such as mutations in the COL5A or COL3A genes. The collagen in connective tissue helps tissues resist deformation. Collagen is an important contributor to the physical strength of skin, joints, muscles, ligaments, blood vessels and visceral organs; abnormal collagen renders these structures more elastic. Depending on the individual, the severity of the mutation can vary from mild to life-threatening. There is no cure, and treatment is supportive, including close monitoring of the digestive, excretory and particularly the cardiovascular systems. Occupational and physical therapy, bracing, and corrective surgery may help with the frequent injuries and pain that tend to develop in certain types of EDS, although ext...

Signs and symptoms

Signs vary widely based on which type of EDS the patient has. In each case, however, the signs are ultimately due to faulty or reduced amounts of collagen. EDS typically affects the joints, skin, and blood vessels. Following is a list of major signs and symptoms. Musculoskeletal: Hyper-flexible joints (It is possible to be very flexible or have "double joints", however, this is not the same as EDS.) Unstable joints that are prone to: sprain, dislocation, subluxation and hyperextension Early onset of advanced osteoarthritis Chronic degenerative joint disease Swan neck deformity of the fingershttp://jhs.sagepub.com/cgi/content/abstract/22/1/128 Boutonniere deformity of the fingers Tearing of tendons or muscles Deformities of the spine, such as: scoliosis (curvature of the spine), kyphosis (a thoracic hump), tethered spinal cord syndrome, occipitoatlantoaxial hypermobility Myalgia (muscle pain) and arthralgia (joint pain), which may be severe Trendelenburg's sign Osgood-Schlatter Disease Skin: Fragile skin that tears easily Easy bruising Redundant skin folds Molluscoid pseudotumors, especially on pressure points Subcutaneous spheroids Cardiovascular: Arterial rupture Valvular heart disease (such as mitral valve prolapse, which creates an increased risk for infective endocarditis during surgery, as well as possibly progressing to a life-threatening degree of severity of the prognosis of mitral valve prolapse)http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=eds3 Dilation and/or rupture of ascending aorta Other manifestations or complications: Hiatial hernia Anal prolapse Collapsed lung (pneumothorax) Nerve compression disorders (carpal tunnel syndrome, acroparesthesia, neuropathy)http://www.answers.com/topic/ehlers-danlos-syndrome Insensitivity to local anesthetics. Arnold–Chiari malformation (brain disorder)http://www.northshorelij.com/workfiles/chiari/J%20Neurosurg%20Spine%20article%20Dec%2007.pdf Platelet aggregatio...
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Harrod syndrome

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

Description

Harrod et al. (1977) reported 2 brothers with an unusual syndrome of mental retardation, unusual facial appearance, large protruding ears, arachnodactyly, hypogenitalism, failure to thrive, and minor anomalies. The younger child also had malrotation of the small bowel and died at the age of 2 months before surgery for pyloric stenosis. Autopsy showed multiple microcysts of the renal cortex. Jurenka and Van Allen (1996) reported the case of a 46-year-old man with striking resemblance to the children described by Harrod et al. (1977). In addition to the features described by Harrod et al. (1977), he had megacolon and varicose veins, suggestive of a connective tissue disorder. An unusual facial appearance consisted of hypotelorism, long nose, highly arched palate, pointed chin, and a small mouth with malocclusion. Both brothers reported by Harrod et al. (1977) had an aberrant subclavian artery, and both had undescended testes and hypospadias. The appearance of the ears was particularly striking, as illustrated by photographs.

Symptoms

Neuro: Mental retardation

Facies: Unusual facial appearance; Pointed chin

Eyes: Hypotelorism

Nose: Long nose

Mouth: High arched palate; Small mouth

Teeth: Malocclusion

Ears: Large protruding ears

Limbs: Arachnodactyly

GU: Hypogenitalism; Undescended testes; Hypospadias; Multiple renal cortical microcysts

Growth: Failure to thrive

GI: Small bowel malrotation; Pyloric stenosis; Megacolon

Vascular: Varicose veins; Aberrant subclavian artery

Inheritance: ? Autosomal recessive
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Harrod syndrome

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

Harrod syndrome is characterized by the association of intellectual deficit, facial dysmorphism (a highly arched palate, pointed chin, and small mouth, hypotelorism, a long nose and large protruding ears), arachnodactyly, hypogenitalism (undescended testes and hypospadias) and failure to thrive. So far, it has been described in three males (including two brothers). The etiology remains unknown and an autosomal recessive mode of transmission has been suggested. Last update: November 2009
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Cerebro-costo-mandibular syndrome

Retrieved: 27-07-2015
Source: GARD (Original article)
Associated genes: cog1

Cerebro-costo-mandibular syndrome

Cerebro-costo-mandibular syndrome (CCMS) is a very rare condition characterized by severe micrognathia (abnormally small jaw), abnormalities of the roof of the mouth (palate), and rib defects. Other signs and symptoms may include intellectual disability and microcephaly (small head size). In some cases, the features cause respiratory problems in early infancy and can be life-threatening. Most cases appear to occur randomly (sporadically), but both autosomal dominant and autosomal recessive inheritance have been reported. No specific gene known to cause the condition has been identified. Treatment and prognosis depend on the features and severity in each affected person
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Cerebro-oculo-facio-skeletal syndrome

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

Cerebro-oculo-facio-skeletal syndrome

Cerebro-oculo-facio-skeletal (COFS) syndrome is a degenerative disorder that primarily involves the brain, eyes, and spinal cord. Affected individuals have mild to severe intellectual disability, severely reduced muscle tone (hypotonia), impaired reflexes, vision impairment, and involuntary eye movements. Children with COFS syndrome have distinctive facial features, including low-set ears, small eyes, small head size (microcephaly), and a small jaw (micrognathia). They may also have abnormalities of the skull, limbs, heart, and kidneys. Individuals with COFS syndrome are often diagnosed at birth. In many cases, the cause of the disorder is unknown. Some children with this condition have mutations in the ERCC1, ERCC2, ERCC5, or ERCC6 gene. When an individual has the features of COFS syndrome and a mutation in the ERCC6 gene, they are said to have Cockayne syndrome type II.  COFS syndrome is inherited in an autosomal recessive manner. Most children with this condition do not live past age 5. Treatment involves supportive care and is based on an individual's symptoms
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Emanuel syndrome

Retrieved: 27-07-2015
Source: GARD (Original article)
Associated genes: cyp11b2, der22t11-22, tbx1

Emanuel syndrome

Emanuel syndrome is a chromosome disorder that causes problems with physical and intellectual development. Signs and symptoms can vary but may include severe intellectual disability; small head size (microcephaly); failure to thrive; cleft palate or high-arched palate; small jaw (micrognathia); congenital heart defects; and abnormalities of the ears, kidneys, and/or male genitals. It is caused by having extra material from chromosomes 11 and 22 in each cell. Almost all people with Emanuel syndrome inherit the extra chromosome material from an unaffected parent with a balanced translocation. Treatment focuses on the specific signs and symptoms in each person
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Trisomy 18

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

Trisomy 18

Trisomy 18 is a chromosome disorder characterized by having 3 copies of chromosome 18 instead of the usual 2 copies. Signs and symptoms include severe intellectual disability; low birth weight; a small, abnormally shaped head; a small jaw and mouth; clenched fists with overlapping fingers; congenital heart defects; and various abnormalities of other organs. Trisomy 18 is a life-threatening condition; many affected people die before birth or within the first month of life. Some children have survived to their teenage years, but with serious medical and developmental problems. Most cases are not inherited and occur sporadically (by chance)
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Isolated Pierre Robin sequence

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

What is isolated Pierre Robin sequence?

Pierre Robin sequence is a set of abnormalities affecting the head and face, consisting of a small lower jaw (micrognathia), a tongue that is placed further back than normal (glossoptosis), and an opening in the roof of the mouth (a cleft palate). This condition is described as a "sequence" because one of its features, an underdeveloped lower jaw (mandible), sets off a sequence of events before birth that cause the other signs and symptoms. Specifically, having an abnormally small jaw affects placement of the tongue and formation of the palate, leading to glossoptosis and cleft palate. The combination of features characteristic of Pierre Robin sequence can lead to difficulty breathing and problems eating early in life. As a result, some affected babies have an inability to grow and gain weight at the expected rate (failure to thrive). In some children with Pierre Robin sequence, growth of the mandible catches up, and these individuals have normal-sized chins. Some people have Pierre Robin sequence as part of a syndrome that affects other organs and tissues in the body, such as campomelic dysplasia or Stickler syndrome. These instances are described as syndromic. When Pierre Robin sequence occurs by itself, it is described as nonsyndromic or isolated. Approximately 20 to 40 percent of cases of Pierre Robin sequence are isolated. Read more about campomelic dysplasia and Stickler syndrome.

How common is isolated Pierre Robin sequence?

Isolated Pierre Robin sequence affects an estimated 1 in 8,500 to 14,000 people.

What genes are related to isolated Pierre Robin sequence?

Changes in the DNA near the SOX9 gene are the most common genetic cause of isolated Pierre Robin sequence. It is likely that changes in other genes, some of which have not been identified, also cause isolated Pierre Robin sequence. The SOX9 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 SOX9 protein regulates the activity ...

Keywords

isolated Pierre Robin sequence,Stomatognathic System Abnormalities,Maxillofacial Abnormalities,Congenital Abnormalities,Craniofacial Abnormalities,Congenital, Hereditary, and Neonatal Diseases and Abnormalities,Musculoskeletal Diseases,Jaw Diseases,Stomatognathic Diseases,Jaw Abnormalities,Musculoskeletal Abnormalities,Pierre Robin Syndrome,Bones, muscles, and connective tissues,Mouth and teeth,Ear, nose, and throat,SOX9,SOX9 gene,glossoptosis micrognathia and cleft palate,Pierre Robin syndrome,Pierre-Robin syndrome,Robin sequence,Robin 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
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Cri-du-chat syndrome

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

What is cri-du-chat syndrome?

Cri-du-chat (cat's cry) syndrome, also known as 5p- (5p minus) syndrome, is a chromosomal condition that results when a piece of chromosome 5 is missing. Infants with this condition often have a high-pitched cry that sounds like that of a cat. The disorder is characterized by intellectual disability and delayed development, small head size (microcephaly), low birth weight, and weak muscle tone (hypotonia) in infancy. Affected individuals also have distinctive facial features, including widely set eyes (hypertelorism), low-set ears, a small jaw, and a rounded face. Some children with cri-du-chat syndrome are born with a heart defect.

How common is cri-du-chat syndrome?

Cri-du-chat syndrome occurs in an estimated 1 in 20,000 to 50,000 newborns. This condition is found in people of all ethnic backgrounds.

What are the genetic changes related to cri-du-chat syndrome?

Cri-du-chat syndrome is caused by a deletion of the end of the short (p) arm of chromosome 5. This chromosomal change is written as 5p-. The size of the deletion varies among affected individuals; studies suggest that larger deletions tend to result in more severe intellectual disability and developmental delay than smaller deletions. The signs and symptoms of cri-du-chat syndrome are probably related to the loss of multiple genes on the short arm of chromosome 5. Researchers believe that the loss of a specific gene, CTNND2, is associated with severe intellectual disability in some people with this condition. They are working to determine how the loss of other genes in this region contributes to the characteristic features of cri-du-chat syndrome. Read more about the CTNND2 gene and chromosome 5.

Can cri-du-chat syndrome be inherited?

Most cases of cri-du-chat syndrome are not inherited. The deletion occurs most often as a random event during the formation of reproductive cells (eggs or sperm) or in early fetal development. Affected people typically have no history of the disorder in their family. About 10 percent of people with cri-du-chat syndrome inherit the chromosome abnormality f...

Keywords

cri-du-chat syndrome,Genetic Diseases, Inborn,Congenital Abnormalities,Congenital, Hereditary, and Neonatal Diseases and Abnormalities,Pathological Conditions, Signs and Symptoms,Nervous System Diseases,Signs and Symptoms,Neurologic Manifestations,Neurobehavioral Manifestations,Chromosome Disorders,Intellectual Disability,Mental Disorders,Mental Disorders Diagnosed in Childhood,Behavior and Behavior Mechanisms,Abnormalities, Multiple,Cri-du-Chat Syndrome,Brain and nervous system,Heart and circulation,CTNND2,CTNND2 gene,5p deletion syndrome,5p- syndrome,cat cry syndrome,chromosome 5p- syndrome,monosomy 5p,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
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Megaepiphyseal dwarfism

Retrieved: 27-07-2015
Source: OMIM (Original article)
Associated genes: col11a2, col2a1

Description

Gorlin et al. (1973) described a seemingly 'new' syndrome in a 9-year-old boy who may have been the product of father-daughter incest. Unusual facies consisted of snub nose, epicanthal folds, and cleft palate. These findings and large joints were evident from birth. The prominence of almost all joints was progressive. Inferior subluxation of both lenses was found at age 9 years and this could be accounted for by the finding of homocystinuria. However, the authors concluded that the child had another recessive disorder resulting from the parental consanguinity.

Symptoms

HEENT: Unusual facies; Snub nose; Epicanthal folds; Cleft palate; Inferior lens subluxation

Skel: Large joints; Short stature

Inheritance: Autosomal recessive; ? variant of Oto-spondylo-megaepiphyseal dysplasia (215150)
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Otospondylomegaepiphyseal dysplasia

Retrieved: 27-07-2015
Source: Orphanet (Original article)
Associated genes: col11a2, col2a1

Otospondylomegaepiphyseal dysplasia (OSMED) is an inborn error of cartilage collagen formation characterized by sensorineural hearing loss, enlarged epiphyses, skeletal dysplasia with disproportionately short limbs, vertebral body anomalies and a characteristic facies. The prevalence is unknown but less than 30 cases have been described in the literature so far. Typical facial features include midface hypoplasia, a short nose with anteverted nares and a flat nasal bridge, a long philtrum, cleft palate/bifid uvula, micrognathia, and hypertelorism. Joint pain and restricted mobility of the metacarpophalangeal joints appear during the second decade of life. The sensorineural hearing loss is generally described as moderate and nonprogressive. Early onset of osteoarthritis has also been reported. OSMED is inherited as an autosomal recessive trait and is classed among the type XI collagenopathies as the majority of reported cases have been associated with homozygous mutations in the COL11A2 gene (6p21.3), encoding the alpha2 chain of type XI collagen. Diagnosis is made on the basis of the clinical phenotype and typical radiographic findings: shortening of the long bones (humerus, radius, ulna, tibia, and fibula) with large epiphyses and metaphyseal flaring, coronal clefting and mild to moderate platyspondyly. OSMED shows significant clinical overlap with Weissenbacher-Zweymuller syndrome (WZS) and Stickler syndrome (see these terms). Whilst OSMED and Stickler syndrome can be distinguished early in life due to the absence of ocular anomalies in OSMED, differentiation of OSMED and WZS (also associated with heterozygous mutations in the COL11A2 gene) may be more problematic. Treatment is symptomatic only, involving closure of the cleft palate, audiometry and adapted management of the hearing loss, and treatment of the joint pain. The prognosis depends on the severity of the osteoarthritis (which may require early joint replacement), hearing loss and joint pain. Expe...
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OSMED

Retrieved: 27-07-2015
Source: GHR (Original article)
Associated genes: col11a2, col2a1

What is OSMED?

Otospondylomegaepiphyseal dysplasia (OSMED) is a skeletal disorder characterized by skeletal abnormalities, distinctive facial features, and severe hearing loss. The condition involves the ears (oto-), affects the bones of the spine (spondylo-), and enlarges the ends (epiphyses) of long bones in the arms and legs. The features of OSMED are similar to those of another skeletal disorder, Weissenbacher-Zweymüller syndrome. People with OSMED are often shorter than average because the bones in their legs are unusually short. Other skeletal features include enlarged joints; short arms, hands, and fingers; and flattened bones of the spine (platyspondyly). People with the disorder often experience back and joint pain, limited joint movement, and arthritis that begins early in life. Severe high-tone hearing loss is common in people with OSMED. Typical facial features include protruding eyes; a flattened bridge of the nose; an upturned nose with a large, rounded tip; and a small lower jaw. Virtually all affected infants are born with an opening in the roof of the mouth (a cleft palate). The skeletal features of OSMED tend to diminish during childhood, but other signs and symptoms, such as hearing loss and joint pain, persist into adulthood. Read more about Weissenbacher-Zweymüller syndrome.

How common is OSMED?

This condition is rare; the prevalence is unknown. Only a few families with OSMED have been reported worldwide.

What genes are related to OSMED?

Mutations in the COL11A2 gene cause OSMED. The COL11A2 gene is one of several genes that provide instructions for the production of type XI collagen. This type of collagen is important for the normal development of bones and other connective tissues that form the body's supportive framework. Mutations in the COL11A2 gene that cause OSMED disrupt the production or assembly of type XI collagen molecules. The loss of type XI collagen prevents bones and other connective tissues from developing properly. Read more about the COL11A2 gene.

Keywords

otospondylomegaepiphyseal dysplasia,Collagen Diseases,Skin and Connective Tissue Diseases,Connective Tissue Diseases,Bones, muscles, and connective tissues,Mouth and teeth,Ear, nose, and throat,type XI collagenopathy,COL11A2,COL11A2 gene,Chondrodystrophy with sensorineural deafness,Insley-Astley syndrome,Mega-epiphyseal dwarfism,Nance-Insley syndrome,Nance-Sweeney chondrodysplasia,Oto-spondylo-megaepiphyseal dysplasia,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
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Otospondylomegaepiphyseal dysplasia

Retrieved: 27-07-2015
Source: WIKIPEDIA (Original article)
Associated genes: col11a2, col2a1
Otospondylomegaepiphyseal dysplasia (OSMED) is an autosomal recessive disorder of bone growth that results in skeletal abnormalities, severe hearing loss, and distinctive facial features. The name of the condition indicates that it affects hearing (oto-) and the bones of the spine (spondylo-), and enlarges the ends of bones (megaepiphyses). The features of OSMED are similar to those of another skeletal disorder, Weissenbacher-Zweymüller syndrome. Otospondylomegaepiphyseal dysplasia is a subtype of collagenopathy, types II and XI.

Diagnosis

The distinctive characteristics of OSMED include severe bone and joint problems and very severe hearing loss. This disorder affects the epiphyses, the parts of the bone where growth occurs. People with the condition are often shorter than average because the bones in their arms and legs are unusually short. Other skeletal signs include enlarged joints, short hands and fingers, and flat bones of the spine (vertebrae). People with the disorder often experience back and joint pain, limited joint movement, and arthritis that begins early in life. Severe high-tone hearing loss is common. Typical facial features include protruding eyes; a sunken nasal bridge; an upturned nose with a large, rounded tip; and a small lower jaw. Some affected infants are born with an opening in the roof of the mouth, which is called a cleft palate.

Pathophysiology

Mutations in the COL11A2 gene cause otospondylomegaepiphyseal dysplasia. The protein made by the COL11A2 gene is involved in the production of type XI collagen. This type of collagen is important for the normal development of bone and other connective tissues. Mutations in the COL11A2 gene lead to a loss of function of this type of collagen, resulting in the signs and symptoms of OSMED. OSMED is inherited in an autosomal recessive pattern, which means the defective gene is located on an autosome, and two copies of the defective gene - one from each parent - must be inherited for a person to be affected by the disorder. The parents of a child with an autosomal recessive disorder are usually not affected but are carriers of one copy of the altered gene. A recessive pattern of inheritance makes OSMED unique among the type II and type XI collagenopathies.

Epidemiology

The frequency of this disorder is unknown, but it is very rare. Only a few families with the condition have been reported.

External links

This article incorporates public domain text from The U.S. National Library of Medicine
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Schilbach-rott syndrome

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

Description

Schilbach-Rott syndrome is an autosomal dominant disorder characterized by hypotelorism, epicanthal folds, cleft palate, dysmorphic facies, and hypospadias in males. The phenotype is variable; mild mental retardation has been reported (summary by Shkalim et al., 2009).

Clinical features

In 10 persons over 5 generations of a family, Schilbach and Rott (1988) found ocular hypotelorism, submucosal cleft palate, and, in males, hypospadias. Other anomalies were blepharophimosis, upslant of palpebral fissures, and a tendency to cutaneous syndactyly of fingers 3 and 4 and toes 2 and 3. One instance of male-to-male transmission was reported in earlier generations in which hypotelorism was said to have been present but was not documented by examination or by photographs.

Joss et al. (2002) described 2 brothers with cleft palate and facial appearance closely resembling the cases described by Schilbach and Rott (1988). One had hypospadias and learning disability and, like his mother, was of short stature.

Becerra-Solano et al. (2007) reported a Mexican father and son with Schilbach-Rott syndrome. The 3.5-year-old son had low Apgar scores at birth along with central cleft palate, hypospadias, and inguinal hernia. He later exhibited delayed psychomotor development. Dysmorphic features included brachycephaly with prominent metopic ridge, right ptosis, blepharophimosis, epicanthal folds, hypotelorism, small nose with high bridge, anteverted small ears with attached lobules, and short neck. His father had similar features without hypospadias. Both individuals also had microcephaly. Becerra-Solano et al. (2007) suggested autosomal dominant inheritance.

De Carvalho et al. (2008) reported a 4-year-old Brazilian girl with blepharophimosis, long face, broad forehead with a high anterior hairline, anteverted and prominent ears, malar hypoplasia, a broad nasal tip and columella, deeply grooved philtrum, small mouth, thin lips, and a long chin. She also had a broad thorax with a pectus carinatum, long and tapering fingers and toes, bilateral clinodactyly of the fourth and fifth fingers, and long, narrow great toes. Expressive language development ...

Symptoms

INHERITANCE: Autosomal dominant

GROWTH: [Height]; Short stature (in some patients)

HEAD AND NECK: [Head]; Small head circumference; Microcephaly; [Face]; Asymmetric face; Micrognathia; [Ears]; Posteriorly rotated ears; Hypoplastic ears; [Eyes]; Hypotelorism; Upslanting palpebral fissures; Blepharophimosis; Epicanthal folds; [Nose]; Long nose; Prominent nose; [Mouth]; Cleft palate; Bifid uvula; Small mouth

GENITOURINARY: [External genitalia, male]; Hypospadias

SKELETAL: [Hands]; Syndactyly; Clinodactyly

NEUROLOGIC: [Central nervous system]; Mental retardation, mild (in some patients); [Behavioral/psychiatric manifestations]; Attention deficit-hyperactivity disorder

MISCELLANEOUS: Variable phenotype
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Stevenson-carey syndrome

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

Clinical features

Stevenson and Carey (2007) described 2 sisters with a multiple congenital anomaly syndrome with mental retardation, Pierre-Robin sequence, and cerebellar hypoplasia. Both sisters had similar craniofacial features including coloboma, microphthalmia, downslanting palpebral fissures, anteverted nares, small mouth with down-turned corners, and Pierre-Robin sequence with cleft palate. Echocardiograms revealed left superior vena cava draining into the coronary sinus. The younger sister also had an atrial septal defect. Skeletal features included camptodactyly of the fingers with the index fingers overlying the third fingers and congenital hip dysplasia. MRIs of both girls demonstrated hypoplastic corpus callosum, enlarged cisterna magna, and cerebellar hypoplasia. Both had significant developmental delay and seizures. Stevenson and Carey (2007) noted phenotypic overlap with the Ritscher-Schinzel (220210) and Toriello-Carey (217980) syndromes but concluded that the distinct pattern of malformations represented a provisionally unique syndrome.

Craft et al. (2010) reported 2 sibs, a girl and a boy, born of consanguineous Pakistani parents, with features reminiscent of 3C syndrome. Both had delayed psychomotor development and dysmorphic facial features, including downslanting palpebral fissures, prominent nasal bridge, micrognathia, and small head size. Both patients and an otherwise unaffected sister had flexion contractures of the fingers; the affected sister also had flexion contractures of the large joints and scoliosis. The affected sister had marked cerebellar vermis hypoplasia, ventricular septal defect, and mitral valve stenosis, but the affected brother did not ha...

Symptoms

INHERITANCE: Autosomal recessive

HEAD AND NECK: [Head]; Brachycephaly; [Ears]; Low-set ears; Posteriorly rotated ears; Narrow ear canals; [Eyes]; Downslanting palpebral fissures; Microphthalmia; Coloboma (iris, optic nerve); [Nose]; Anteverted nares; Prominent nasal tip; Hypoplastic nasal alae; [Mouth]; Pierre-Robin sequence; Small mouth; Downturned corners of mouth

CARDIOVASCULAR: [Heart]; Atrial septal defect; Left superior vena cava draining to coronary sinus

RESPIRATORY: Central hypoventilation

ABDOMEN: [Gastrointestinal]; Gastroesophageal reflux, severe; Constipation

GENITOURINARY: Urinary tract infections

SKELETAL: [Spine]; Scoliosis; [Pelvis]; Congenital hip dysplasia; [Limbs]; Contractures (elbows, wrists, knees, ankles); [Hands]; Camptodactyly; Second finger overlap with third finger; Hypoplastic flexion creases

SKIN, NAILS, HAIR: [Skin]; Hypoplastic flexion creases

NEUROLOGIC: [Central nervous system]; Developmental delay; Mental retardation; Seizures; Hypoplastic corpus callosum; Enlarged cisterna magna; Cerebellar hypoplasia

PRENATAL MANIFESTATIONS: [Placenta and umbilical cord]; Two-vessel cord
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Bamforth-Lazarus syndrome

Retrieved: 27-07-2015
Source: Orphanet (Original article)
Associated genes: foxe1, bche, tgfb3, msx1

Bamforth-Lazarus syndrome is a very rare syndrome of congenital hypothyroidism characterized by thyroid dysgenesis (in most cases athyreosis), cleft palate and spiky hair, with or without choanal atresia, and bifid epiglottis. Facial dysmorphism and porencephaly have been reported in isolated cases. Only 8 patients from 6 families have been reported to date. Newborns present at birth with thyroid dysgenesis (in most cases athyreosis) leading to congenital hypothyroidism that manifests with lethargy, poor feeding, macroglossia, cold or mottled skin, persistent jaundice, and umbilical hernia. Neonatal hyperbilirubinemia is also common. All newborns with Bamforth- Lazarus syndrome have a cleft palate and spiky hair. Some may also present with choanal atresia and bifid epiglottis. Facial dysmorphism, consisting of microcephaly, hypertelorism, anteverted nares, narrow nasal bridge, low-set ears, small jaw and retrognathia, has been reported in one case. Porencephaly was also recently described in one case. Bamforth-Lazarus syndrome is due to homozygous loss-of-function missense mutations located within the forkhead domain of the FOXE1 gene (9q22), encoding thyroid transcription factor 2 (TTF-2). TTF-2 is expressed in the thyroid gland (as well as elsewhere like the tongue, epiglottis and palate) and is thought to play a crucial role in thyroid morphogenesis. Cases reported so far have all been due to homozygous loss-of-function mutations apart from one case described recently with a novel FOXE1 homozygous mutation causing increased thyroid gene expression. Diagnosis is based on clinical findings of congenital hypothyroidism with cleft palate and spiky hair along with findings of thyroid ultrasonography (USG) and computed tomography examination. Thyroid tissue is either completely absent or non-functional. Serum thyroid stimulation hormone (TSH) levels should be measured (levels will be elevated on newborn screening filter paper test, as is seen in all cases of a...
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Bowen-Conradi syndrome

Retrieved: 27-07-2015
Source: GHR (Original article)
Associated genes: emg1

What is Bowen-Conradi syndrome?

Bowen-Conradi syndrome is a disorder that affects many parts of the body and is usually fatal in infancy. Affected individuals have a low birth weight, experience feeding problems, and grow very slowly. Their head is unusually small overall (microcephaly), but is longer than expected compared with its width (dolicocephaly). Characteristic facial features include a prominent, high-bridged nose and an unusually small jaw (micrognathia) and chin. Affected individuals typically have pinky fingers that are curved toward or away from the ring finger (fifth finger clinodactyly) or permanently flexed (camptodactyly), feet with soles that are rounded outward (rocker-bottom feet), and restricted joint movement. Other features that occur in some affected individuals include seizures; structural abnormalities of the kidneys, heart, brain, or other organs; and an opening in the lip (cleft lip) with or without an opening in the roof of the mouth (cleft palate). Affected males may have the opening of the urethra on the underside of the penis (hypospadias) or undescended testes (cryptorchidism). Babies with Bowen-Conradi syndrome do not achieve developmental milestones such as smiling or sitting, and they usually do not survive more than 6 months.

How common is Bowen-Conradi syndrome?

Bowen-Conradi syndrome is common in the Hutterite population in Canada and the United States; it occurs in approximately 1 per 355 newborns in all three Hutterite sects (leuts). A few individuals from outside the Hutterite community with signs and symptoms similar to Bowen-Conradi syndrome have been described in the medical literature. Researchers differ as to whether these individuals have Bowen-Conradi syndrome or a similar but distinct disorder.

What genes are related to Bowen-Conradi syndrome?

Bowen-Conradi syndrome is caused by a mutation in the EMG1 gene. This gene provides instructions for making a protein that is involved in the production of cellular structures called ribosomes, which process the cell's genetic inst...

Keywords

Bowen-Conradi syndrome,Abnormalities, Multiple,Congenital Abnormalities,Congenital, Hereditary, and Neonatal Diseases and Abnormalities,Brain and nervous system,Mouth and teeth,ribosomal biogenesis,ribosome biogenesis,ribosomopathy,EMG1,EMG1 gene,Bowen-Conradi Hutterite syndrome,Bowen Hutterite syndrome,Bowen syndrome Hutterite type,BWCNS,Hutterite 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,congenital,heritable disorders,inherited disorders,heritable diseases,inherited diseases,family disorders,family diseases
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Fumarase deficiency

Retrieved: 27-07-2015
Source: GHR (Original article)
Associated genes: fh, chpt1, dhdds
Fumarase deficiency

What is fumarase deficiency?

Fumarase deficiency is a condition that primarily affects the nervous system, especially the brain. Affected infants may have an abnormally small head size (microcephaly), abnormal brain structure, severe developmental delay, weak muscle tone (hypotonia), and failure to gain weight and grow at the expected rate (failure to thrive). They may also experience seizures. Some people with this disorder have unusual facial features, including a prominent forehead (frontal bossing), low-set ears, a small jaw (micrognathia), widely spaced eyes (ocular hypertelorism), and a depressed nasal bridge. An enlarged liver and spleen (hepatosplenomegaly) may also be associated with this disorder, as well as an excess of red blood cells (polycythemia) or deficiency of white blood cells (leukopenia) in infancy. Affected individuals usually survive only a few months, but a few have lived into early adulthood.

How common is fumarase deficiency?

Fumarase deficiency is a very rare disorder. Approximately 100 affected individuals have been reported worldwide. Several were born in an isolated religious community in the southwestern United States.

What genes are related to fumarase deficiency?

The FH gene provides instructions for making an enzyme called fumarase (also known as fumarate hydratase). Fumarase participates in an important series of reactions known as the citric acid cycle or Krebs cycle, which allows cells to use oxygen and generate energy. Specifically, fumarase helps convert a molecule called fumarate to a molecule called malate. Mutations in the FH gene disrupt the enzyme's ability to help convert fumarate to malate, interfering with the function of this reaction in the citric acid cycle. Impairment of the process that generates energy for cells is particularly harmful to cells in the developing brain, and this impairment results in the signs and symptoms of fumarase deficiency. Read more about the FH gene.

How do people inherit fumarase deficiency?

This condition is inherited in an autosomal recessive pattern, which means both copie...

Keywords

fumarase deficiency,Metabolism, Inborn Errors,Nutritional and Metabolic Diseases,Genetic Diseases, Inborn,Congenital, Hereditary, and Neonatal Diseases and Abnormalities,Metabolic Diseases,Brain and nervous system,Food, nutrition, and metabolism,polygamists' Down's,FH,FH gene,fumarate hydratase deficiency,fumaric aciduria,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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Periodic paralysis

Retrieved: 27-07-2015
Source: WIKIPEDIA (Original article)
Periodic paralysis (also known as Myoplegia paroxysmalis familiaris) is a group of rare genetic diseases that lead to weakness or paralysis (rarely death) from common triggers such as cold, heat, high carbohydrate meals, not eating, stress or excitement and physical activity of any kind. The underlying mechanism of these diseases are malfunctions in the ion channels in skeletal muscle cell membranes that allow electrically charged ions to leak in or out of the muscle cell, causing the cell to depolarize and become unable to move (a channelopathy). The symptoms of periodic paralysis can also be caused by hyperthyroidism, and are then labeled thyrotoxic periodic paralysis; however, if this is the underlying condition there are likely to be other characteristic manifestations, enabling a correct diagnosis.

Types

Periodic paralysis is an autosomal dominant myopathy with considerable variation in penetrance, leading to a spectrum of familial phenotypes (only one parent needs to carry the gene mutation to affect the children, but not all family members who share the gene are affected to the same degree). Specific diseases include: Hypokalemic periodic paralysis (), where potassium leaks into the muscle cells from the bloodstream. Hyperkalemic periodic paralysis (), where potassium leaks out of the cells into the bloodstream. Paramyotonia congenita (), a form which often accompanies hyperkalemic periodic paralysis, but may present alone. The primary symptom of paramyotonia congenita is muscle contracture which develops during exercise or activity. Paramyotonia congenita attacks may also be triggered by a low level of potassium in the bloodstream. This means people with both hyperkalemic periodic paralysis and paramyotonia congenita can have attacks with fluctuations of potassium up or down. Andersen-Tawil syndrome (), a form of periodic paralysis that includes significant heart rhythm problems, fainting and risk of sudden death. Potassium levels may...

Diagnosis

This disease is unusually difficult to diagnose. Patients often report years of wrong diagnosis and treatments that made them worse instead of better. Part of this may be that migraines are present in up to 50% of patients and can cause a confusing array of symptoms including headaches, speech difficulties and visual, auditory or sensory auras. DNA testing is available for only a half dozen common gene mutations, while dozens of known mutations are possible but are not routinely tested. Electromyography (EMG) findings are not specific. The old glucose/insulin provocative testing can cause life-threatening symptoms and should not be used. Also of note is that potassium levels do not have to range outside of normal limits to cause serious, even life-threatening paralysis. These diseases are not the same as having a very low level of potassium (hypokalemia) or high potassium (hyperkalemia) and must not be treated as such. The total body store of potassium is usually normal; it is just in the wrong place.

Catel–Manzke syndrome

Retrieved: 27-07-2015
Source: WIKIPEDIA (Original article)
Catel–Manzke syndrome is a rare genetic disorder characterized by distinctive abnormalities of the index fingers; the classic features of Pierre Robin syndrome; occasionally with additional physical findings. Pierre Robin syndrome refers to a sequence of abnormalities that may occur as a distinct syndrome or as part of another underlying disorder. Pierre Robin syndrome is characterized by an unusually small jaw (Micrognathia), downward displacement or retraction of the tongue (Glossoptosis), and incomplete closure of the roof of the mouth (Cleft palate). It is also linked to Hyper Mobility Syndrome.

Presentation

Infants with Catel–Manzke syndrome have an extra (supernumerary), irregularly shaped bone known as a Hyperphalangy located between the first bone of the index finger (proximal phalanx) and the corresponding bone within the body of the hand (second metacarpal). As a result, the index fingers may be fixed in an abnormally bent position (clinodactyly). In some rare cases, additional abnormalities of the hands may also be present. Due to the presence of micrognathia, glossoptosis, and cleft palate, affected infants may have feeding and breathing difficulties; growth deficiency; consistent middle ear infections (otitis media); and other complications. In addition, some infants with the syndrome may have structural abnormalities of the heart that are present at birth (congenital heart defects). The range and severity of symptoms and findings may vary from case to case. Catel–Manzke syndrome usually appears to occur randomly, for unknown sporadic reasons.

Genetic prevalence

Currently there are only around 26 people in the world that are known to have this rare condition. Inheritance is thought to be X-linked recessive.
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Blepharophimosis intellectual disability syndromes

Retrieved: 27-07-2015
Source: GARD (Original article)
Associated genes: kat6b, opa1

Blepharophimosis intellectual disability syndromes

Blepharophimosis intellectual disability syndromes refers to a group of syndromes, including Ohdo syndrome and Say Barber Biesecker Young-Simpson syndrome, that are characterized by narrow eye openings (blepharophimosis), drooping of the upper eye lids (ptosis) and intellectual disability. Dr. Ohdo published an article in 1986 describing the first three cases of this syndrome (in a brother, sister, and cousin). Since that time many other case reports describing people with similar (yet variable) features have been reported. The syndromes usually occur sporadically. In most cases the underlying cause can not be determined

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

Description

In 4 generations of a family, Hall et al. (1975) observed a syndrome of small mouth and jaw with limited jaw movement disappearing by adulthood but with horizontal depression above the chin; mild microcephaly; ears missing the antihelix; and severe flexion contractures of the hands and feet, leading to subluxation of the fingers and clubfeet in the most severely affected child. There was no male-to-male transmission.

Hall et al. (1982) reported 13 additional unrelated patients with a disorder similar to that described by Hall et al. (1975). They termed the disorder distal arthrogryposis type IIe. Clinical features in all patients included trismus and an unusual camptodactyly in the newborn period with hyperextension of the metacarpophalangeal joint, distal flexion contractures, and variations in the degree of severity. All patients also had hip and feet involvement, and wrists were commonly flexed. Other variable features included mild developmental delay, micrognathia, horizontal groove on the chin, facial asymmetry, reduced facial expression, and high-arched palate. The inheritance pattern in 3 families was consistent with autosomal dominance. Average paternal age at conception was 36.

This disorder shows phenotypic overlap with trismus-pseudocamptodactyly syndrome (158300).

Symptoms

Mouth: Small mouth; Small jaw; Limited jaw movement; Horizontal depression above the chin

Head: Mild microcephaly

Ears: Antihelix absent

Limbs: Severe flexion contractures of hands and feet; Subluxation of fingers; Clubfeet

Inheritance: Autosomal dominant


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

Description

The large number of distinct types of the Ehlers-Danlos syndrome that have already been identified indicates great heterogeneity, but clearly that heterogeneity is not exhausted by the present classification. Some of the unclassified families are apparently recessive (see 225320); some, such as that reported by Friedman and Harrod (1982), are seemingly dominant. These authors reported a mother and son with large hernias, positional foot deformities, thoracic deformity, asthma, and eczematoid dermatitis. Both had facial asymmetry, prominent nasal bridge and small jaw. The mother had severe thoracolumbar kyphoscoliosis and 'cigarette paper' scars over the legs. She died of dissecting aortic aneurysm and at autopsy had cystic medial necrosis of the aorta and myxomatous degeneration and elongation of the mitral and tricuspid valves. McKusick (1972) observed dissecting aortic aneurysm in type VI EDS (225400). Loose-jointedness, stretchable skin, Gorlin sign (tip of tongue to tip of nose) and a few papyraceous scars occurred in a man who died of dissecting aneurysm, as did his sister and mother who showed similar systemic signs.

Symptoms

Abdomen: Hernias

Limbs: Positional foot deformities

Thorax: Thoracic deformity

Pulmonary: Asthma

Skin: Eczematoid dermatitis; Stretchable skin; Cigarette-paper scars

Facies: Facial asymmetry; Prominent nasal bridge; Small jaw; Gorlin sign (tip of tongue to tip of nose)

Spine: Thoracolumbar kyphoscoliosis

Joints: Loose-jointedness

Vascular: Dissecting aortic aneurysm

Lab: Cystic medial necrosis of the aorta; Myxomatous valvular degeneration

Inheritance: Autosomal dominant form(s); genetic heterogeneity


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

Clinical features

Bacha and Hoo (2001) described a brother and sister of a Bosnian refugee family with similar clinical features, including sparse hair in the first year of life, prominent nose, small mouth, micrognathia, high-arched palate or cleft palate, crumpled upper helices, flexion limitation of the distal interphalangeal joints of the fingers, and mild developmental delay. The authors suggested that this represented a distinct entity with autosomal recessive inheritance.


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

Escher Hirt syndrome

Escher-Hirt syndrome is characterized by small ears with thickened ear lobes, a small jaw, and conductive hearing loss due to ear abnormalities. It has only been described in a few families. Escher-Hirt syndrome is inherited in an autosomal dominant pattern


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

Hanhart syndrome

Hanhart syndrome is a rare condition that primarily affects the craniofacial region and the limbs (arms and legs). People affected by this condition are often born with a short, incompletely developed tongue; absent or partially missing fingers and/or toes; abnormalities of the arms and/or legs; and an extremely small jaw. The severity of these physical abnormalities varies greatly among affected people, and children with this condition often have some, but not all, of the symptoms. The cause of Hanhart syndrome is not fully understood. Treatment depends on the signs and symptoms present in each person


Retrieved: 27-07-2015
Source: GHR (original)
Associated genes: chrng, tpm2, gbe1

What is multiple pterygium syndrome?

Multiple pterygium syndrome is a condition that is evident before birth with webbing of the skin (pterygium) at the joints and a lack of muscle movement (akinesia) before birth. Akinesia frequently results in muscle weakness and joint deformities called contractures that restrict the movement of joints (arthrogryposis). As a result, multiple pterygium syndrome can lead to further problems with movement such as arms and legs that cannot fully extend. The two forms of multiple pterygium syndrome are differentiated by the severity of their symptoms. Multiple pterygium syndrome, Escobar type (sometimes referred to as Escobar syndrome) is the milder of the two types. Lethal multiple pterygium syndrome is fatal before birth or very soon after birth. In people with multiple pterygium syndrome, Escobar type, the webbing typically affects the skin of the neck, fingers, forearms, inner thighs, and backs of the knee. People with this type may also have arthrogryposis. A side-to-side curvature of the spine (scoliosis) is sometimes seen. Affected individuals may also have respiratory distress at birth due to underdeveloped lungs (lung hypoplasia). People with multiple pterygium syndrome, Escobar type usually have distinctive facial features including droopy eyelids (ptosis), outside corners of the eyes that point downward (downslanting palpebral fissures), skin folds covering the inner corner of the eyes (epicanthal folds), a small jaw, and low-set ears. Males with this condition can have undescended testes (cryptorchidism). This condition does not worsen after birth, and affected individuals typically do not have muscle weakness later in life. Lethal multiple pterygium syndrome has many of the same signs and symptoms as the Escobar type. In addition, affected fetuses may develop a buildup of excess fluid in the body (hydrops fetalis) or a fluid-filled sac typically found on the back of the neck (cystic hygroma). Indiv...

Keywords

multiple pterygium syndrome,Skin Diseases, Genetic,Genetic Diseases, Inborn,Skin Diseases,Skin and Connective Tissue Diseases,Congenital, Hereditary, and Neonatal Diseases and Abnormalities,Bones, muscles, and connective tissues,Skin, hair, and nails,arthrogryposis multiplex congenita,prenatal myasthenia,CHRNA1,CHRNA1 gene,CHRND,CHRND gene,CHRNG,CHRNG gene,RAPSN,RAPSN gene,Escobar syndrome,familial pterygium syndrome,pterygium 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,congenital,heritable disorders,inherited disorders


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

Acrogeria, Gottron type

Acrogeria, Gottron type is a premature aging syndrome. Characteristic signs include fragile, thin skin on the hands and feet. Other parts of the body (e.g., face, forearms, and lower legs) are variably affected. It is generally considered to be a mild, nonprogressive, congenital form of skin atrophy due to the loss of the fatty tissue directly under the skin. Other symptoms reported in individual cases include small hands and feet, prominent veins on the chest, small stature, small jaw, premature senility, premature hair greying, endocrine disturbances, and cataracts. Currently the cause of this condition is unknown


Retrieved: 27-07-2015
Source: Orphanet (original)
Associated genes: b4galt7, dcn, prg2, tgfb1

Ehlers-Danlos syndrome, progeroid type (EDS-PF) is a form of Ehlers-Danlos syndrome (EDS; see this term) characterized by a premature aging with sparse hair, macrocephaly, loose elastic skin, failure to thrive, joint laxity, psychomotor retardation, hypotonia, and defective wound healing with atrophic scars. Last update: January 2014


Retrieved: 27-07-2015
Source: OMIM (original)
Associated genes: fam20c

Description

A number sign (#) is used with this entry because of evidence that Raine syndrome is caused by homozygous or compound heterozygous mutation in the FAM20C gene (611061) on chromosome 7p22.Raine syndrome is a neonatal osteosclerotic bone dysplasia of early and aggressive onset that usually results in death within the first few weeks of life, although there have been some reports of survival into childhood. Radiographic studies show a generalized increase in the density of all bones and a marked increase in the ossification of the skull. The increased ossification of the basal structures of the skull and facial bones underlies the characteristic facial features, which include narrow prominent forehead, proptosis, depressed nasal bridge, and midface hypoplasia. Periosteal bone formation is also characteristic of this disorder and differentiates it from osteopetrosis and other known lethal and nonlethal osteosclerotic bone dysplasias. The periosteal bone formation typica...

Symptoms

INHERITANCE: Autosomal recessive

GROWTH: [Height]; Short stature

HEAD AND NECK: [Head]; Microcephaly; Brachycephaly; Turribrachycephaly; Plagiocephaly (in some patients); Wide fontanelles; [Face]; Craniofacial dysplasia; Midface hypoplasia; 'Fishlike' facies; Choanal atresia or choanal stenosis; Micrognathia; Prognathism (in some patients); [Ears]; Low-set ears; Dysplastic ears (in some patients); Posteriorly rotated ears (in some patients); Protruding ears (in some patients); Hearing loss, mixed (in some patients); [Eyes]; Exophthalmos; Downslanting palpebral fissures; Hypertelorism (in some patients); Arched eyebrows (in some patients); [Nose]; Hypoplastic nose; Depressed nasal bridge; [Mouth]; Gingival hyperplasia; Cleft palate; High palate; Small mouth; Wide mouth (in some patients); Large protruding tongue; [Teeth]; Abnormal teeth (in some patients); Natal teeth (in some patients); Small teeth (in some patients); Enamel dysplasia (in some patients); [Neck]; Short neck

RESPIRATORY: [Lung]; Pulmonary hypoplasia

CHEST: [External features]; Pectus excavatum (in some patients); Small thorax; [Ribs, sternum, clavicles, and scapulae]; Multiple fracture-like rib lesions

GENITOURINARY: [External genitalia, male]; Microscrotum (in some patients); [Kidneys]; Decreased tubular resorption of phosphate (in some patients); Hydronephrosis (in some patients); Double renal pelvis (in some patients); Renal cortex calcification (in some patients); [Ureters]; Hydroureter, bilateral (in some patients); Stenotic ostia of ureters (in some patients)

SKELETAL: Osteosclerosis, generalized; Arthrogryposis (rare); [Spine]; Absence of ossification of vertebral bodies C3 to C5 (rare); Vertebral segmentation defects (rare); [Skull]; Osteosc...


Retrieved: 27-07-2015
Source: OMIM (original)
Associated genes: tpm2, myh3, tnnt3

Description

A number sign (#) is used with this entry because distal arthrogryposis type 1A (DA1A) is caused by heterozygous mutation in the TPM2 gene (190990) on chromosome 9p13.The distal arthrogryposes are a group of disorders that mainly involve the distal parts of the limbs. They are characterized by congenital contractures of 2 or more different body areas without a primary neurologic or muscle disease. The prototypic distal arthrogryposis is type 1 (DA1), which is characterized largely by camptodactyly and clubfoot. Hypoplasia and/or absence of some interphalangeal creases is common. The shoulders and hips are less frequently affected. While the pattern of affected joints is consistent, the degree to which the joints are affected is highly variable, with equinovarus deformities ranging from mild to severe and hand involvement ranging from isolated hypoplasia of the distal interphalangeal crease of the fifth digit to severely clenched fists and ulnar deviation of the wrist. The various phenotypic forms of distal arthrogryposis are classified hierarchically according to the proportion of features they share with one another and are designated DA1 through DA10 (summary by Bamshad et al., 2009).

There are other forms of arthrogryposis multiplex congenita (AMC), including a lethal congenital form (see LCCS1, 253310).

- Genetic Heterogeneity of Distal Arthrogryposes

Distal arthrogryposis type 1 includes DA1A, caused by mutation in the TPM2 gene, and DA1B (614335), caused by mutation in the MYBPC1 gene (160794) on chromosome 12q23.2. Other forms include DA2A (Freeman-Sheldon syndrome, 193700), caused by mutation in the MYH3 gene (160720) on chromosome 17p13.1; DA2B (Sheldon-Hall syndrome, 601680), caused by mutation in MYH3, the TNNT3 gene (600692) on chromosome 11p15.5, the TNNI2 gene (191043), also on 11p15.5, or TPM2 (190990) on chromosome 9p13; DA3 (Gordon syndrome, 114300) and DA5 (108145), caused by mutation in...

Symptoms

INHERITANCE: Autosomal dominant

CHEST: [Ribs, sternum, clavicles, and scapulae]; Stiff shoulders

SKELETAL: [Spine]; Mild scoliosis; [Pelvis]; Hip flexion contractures; Congenital hip dislocations; Decreased hip abduction; [Limbs]; Elbow flexion contractures; Knee flexion contractures; [Hands]; Tightly clenched fists (neonate); Camptodactyly (adult); Ulnar deviation (adult); Absent distal interphalangeal creases; Single transverse palmar creases; [Feet]; Talipes equinovarus; Calcaneovalgus deformities; Vertical talus

SKIN, NAILS, HAIR: [Skin]; Absent distal interphalangeal creases; Single transverse palmar creases

NEUROLOGIC: [Central nervous system]; Normal intelligence

MISCELLANEOUS: Marked intrafamilial and interfamilial variability; Most frequently affected joints - hands (98%) and feet (88%); Genetic heterogeneity (see 601680)

MOLECULAR BASIS: Caused by mutations in the tropomyosin 2 gene (TPM2, 190990.0001)


Retrieved: 27-07-2015
Source: OMIM (original)
Associated genes: chrng, rapsn, dok7, gbe1

Description

A number sign (#) is used with this entry because biallelic mutations in the RAPSN (601592), DOK7 (610285), and MUSK (601296) genes have been identified in patients with a fetal akinesia deformation sequence (FADS) phenotype.

As mutations in these genes have been associated with congenital myasthenic syndromes (see, e.g., CMS1A; 601462), the disorders in these patients likely represent extreme phenotypes of CMS (Vogt et al., 2009).The fetal akinesia deformation sequence (FADS) refers to a clinically and genetically heterogeneous constellation of features including fetal akinesia, intrauterine growth retardation, arthrogryposis, and developmental anomalies, including lung hypoplasia, cleft palate, and cryptorchidism (Vogt et al., 2009). It shows phenotypic overlap with the lethal form of multiple pterygium syndrome (see 253290).

Nomenclature

Although early descriptions by Pena and Shokeir (1974, 1976) resulted in the eponym, Moessinger (1983), Hall (1986), and Hageman et al. (1987) noted that Pena-Shokeir is not a specific unitary diagnosis or syndrome, but rather a description of a clinically and genetically heterogeneous phenotype resulting from fetal ak...

Symptoms

INHERITANCE: Autosomal recessive

GROWTH: [Other]; Small for gestational age; Intrauterine growth retardation

HEAD AND NECK: [Face]; Rigid, expressionless face; Long philtrum; Micrognathia; [Ears]; Small, posteriorly rotated ears; Poorly folded ears; [Eyes]; Prominent eyes; Hypertelorism; Telecanthus; Short palpebral fissures; Ptosis; [Nose]; Depressed nasal tip; [Mouth]; Small mouth; High arched palate; Cleft palate; [Neck]; Short neck

RESPIRATORY: [Lung]; Pulmonary hypoplasia

CHEST: [External features]; Small thorax; [Ribs, sternum, clavicles, and scapulae]; Thin ribs

ABDOMEN: [Gastrointestinal]; Short-gut syndrome

GENITOURINARY: [Internal genitalia, male]; Cryptorchidism

SKELETAL: [Pelvis]; Hip ankylosis; [Limbs]; Elbow ankylosis; Knee ankylosis; Thin, gracile long bones; [Hands]; Ulnar deviation of hands; Camptodactyly; Absent or sparse dermal ridges; [Feet]; Ankle ankylosis; Rocker-bottom feet; Talipes equinovarus

MUSCLE, SOFT TISSUE: Neurogenic muscle atrophy

NEUROLOGIC: [Central nervous system]; Hydrocephalus; Microgyria; Cerebellar hypoplasia; Absent septum pellucidum; Cavum septum pellucidum

PRENATAL MANIFESTATIONS: [Amniotic fluid]; Polyhydramnios; [Placenta and umbilical cord]; Small or abnormal placenta; Short umbilical cord; [Delivery]; Premature birth; Stillborn (30%)

MOLECULAR BASIS: Caused by mutation in the 43-kD receptor-association protein of the synapse, gene (RAPSN, 601592.0013); Caused by mutation in the downstream of tyrosine kinase 7 gene (DOK7, 610285.0009); Caused by mutation in the skeletal muscle receptor tyrosine kinase gene (MUSK, 601296.0006)


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

Description

In a male and female offspring of healthy first-cousin Pakistani parents, Clayton-Smith and Donnai (1989) described a similar pattern of unusual facial features, limb malformations, and postnatal-onset ichthyosis. The male had a small mouth with thin upper lip and a midline groove in the lower lip. In both children the fingers were tapering and lacked distal flexion creases. The daughter had a large gap between the second and third fingers.

Symptoms

Skin: Postnatal-onset ichthyosis

HEENT: Small mouth; Thin upper lip; Midline groove in lower lip

Limbs: Tapered fingers; Distal finger flexion creases absent; Gap between second and third fingers

Inheritance: Autosomal recessive

Treacher Collins syndrome

Treacher Collins syndrome (TCS) is a condition that affects the development of bones and other tissues in the face. The signs and symptoms of this disorder vary greatly, ranging from almost unnoticeable to severe. Most affected people have underdeveloped facial bones, particularly the cheek bones, and a very small jaw and chin (micrognathia). Other features may include cleft palate, eye abnormalities, and hearing loss. TCS may be caused by mutations in the TCOF1, POLR1C, or POLR1D genes. When it is due to the TCOF1 or POLR1D gene, it is inherited in an autosomal dominant manner. About 60% of these cases are due to a new mutation in the gene and are not inherited from a parent. When it is due to the POLR1C gene, it is inherited in an autosomal recessive manner. In some cases, the genetic cause of the condition is unknown


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

Growth delay - hydrocephaly - lung hypoplasia, also named Game-Friedman-Paradice syndrome, is a rare developmental disorder described in 4 sibs so far and characterized by delayed fetal growth, hydrocephaly with patent aqueduct of Sylvius, underdeveloped lungs and various other anomalies such as small jaw, intestinal malrotation, omphalocele, shortness of lower limbs, bowed tibias and foot deformities. Last update: February 2012


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

Clinical features

Among the children of presumably unrelated parents who, however, came from lines that had been located in a rather small town for a long time, Sonoda et al. (1988) described 2 boys and a girl with a syndrome of congenital heart disease, round face with depressed nasal bridge, small mouth, short stature, developmental retardation, relatively dark skin, and high axial triradius in the dermatoglyphic analysis. Pulmonary valvular stenosis was diagnosed in 1 of the children; in a second, ventricular septal defect, which was thought to have closed spontaneously, was diagnosed, and the same lesion may have been present in the third child.

Symptoms

Cardiac: Congenital heart defect; Pulmonary valvular stenosis; Ventricular septal defect

HEENT: Round face; Depressed nasal bridge; Small mouth

Growth: Short stature

Neuro: Mental retardation,

Skin: Dark skin; High axial triradius

Inheritance: Autosomal recessive


Retrieved: 27-07-2015
Source: WIKIPEDIA (original)
Microstomia (micro- a combining form meaning small + -stomia a combining form meaning mouth = (abnormally) "small mouth") is a clinical feature of many craniofacial syndromes, including Freeman-Sheldon syndrome and Sheldon-Hall syndromes (or distal arthrogryposis multiplex congenita). It may present with whistling-face feature, as well, as in Freeman-Sheldon syndrome. In this syndrome, it impairs alimentation and may require repeated oral surgeries (called commissurotomy) to improve function. It can also be a feature of systemic scleroderma.


Retrieved: 27-07-2015
Source: Orphanet (original)
Associated genes: chst14

Ehlers-Danlos syndrome, musculocontractural type (MCEDS) is a form of Ehlers-Danlos syndrome (EDS; see this term) characterized by distinct craniofacial features, multiple contractures, progressive joint and skin laxity, adducted thumb, talipes equinovarus, hemorrhagic diathesis and multisystem fragility-related manifestations. Last update: January 2014


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

This syndrome is characterised by craniosynostosis, intellectual deficit, short stature, facial dysmorphism (oval face with almond-shaped palpebral fissures, droopy eyelids and a small nose) and minor distal anomalies. It has been described in 10 patients. Transmission is autosomal dominant and the syndrome is associated with partial duplication of the long arm of chromosome 5 (5q35-5qter). Last update: September 2007


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

Description

Teebi and Shaltout (1989) described a syndrome of craniofacial anomalies, abnormal hair, camptodactyly, and caudal appendage in the daughter of consanguineous Arab parents. Craniofacial anomalies included scaphocephaly with prominent occiput and bitemporal depression, hypertelorism, ptosis and blepharophimosis, bulbous nose with hypoplastic alae nasi, small mouth, and abnormal teeth. Froster et al. (1993) reported on a second family with the same pattern of anomalies occurring in a liveborn female and 3 spontaneously aborted fetuses. Additional findings in their cases included unilateral microphthalmia and kidney anomalies. The parents were first cousins of Tunisian descent.


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

Clinical features

Giannotti et al. (1997) described a father and son with a progeroid syndrome characterized by an unusual facial appearance, sparse subcutaneous fat, and hand anomalies including syndactyly, camptodactyly, and clinodactyly ('finger deviation'). Mild mental retardation, microcephaly, and congenital heart defect were found only in the son. The heart defect in the son was tetralogy of Fallot, which was corrected at the age of 4 years. At the age of 7, he showed sparse hair, prominent veins (particularly over the scalp and limbs), frontal bossing, upslanting palpebral fissures, bilateral blepharophimosis, prominent nose, short philtrum, small mouth, thin lips, rounded chin, and large, prominent, abnormally modeled ears, with folded helix, and prominent antehelix and antitragus. The fingers were long with partial cutaneous syndactyly of fingers 2 and 3 and clinocamptodactyly of the fifth fingers. Audiometric examination showed bilateral conductive deafness. The father was the first child of healthy, nonconsanguineous parents; his father was 33 and mother 28 years of age at the time of his birth. At the time of evaluation he was 48 years old. His facial anomalies were said to be superimposable to those found in his son, including blepharophimosis, prominent thin nose, short philtrum, small mouth, thin lips, and long prominent ears. There was radial deviation of the third fingers, ulnar deviation of the fourth fingers, and camptodactyly of the fifth fingers. Subcutaneous fat was sparse and a reticular venous pattern was prominent.

Symptoms

INHERITANCE: Autosomal dominant

HEAD AND NECK: [Head]; Microcephaly; [Face]; Short philtrum; Frontal bossing; [Ears]; Prominent ears; Conductive hearing loss; [Eyes]; Blepharophimosis; Upslanting palpebral fissures; [Nose]; Prominent nose; [Mouth]; Thin lips; Small mouth

CARDIOVASCULAR: [Heart]; Tetralogy of Fallot

SKELETAL: [Hands]; Long fingers; Partial cutaneous syndactyly (2-3 fingers); Fifth finger camptodactyly; Fifth finger clinodactyly

SKIN, NAILS, HAIR: [Skin]; Prominent veins (especially over scalp and limbs); [Hair]; Sparse hair

MUSCLE, SOFT TISSUE: Sparse subcutaneous fat

NEUROLOGIC: [Central nervous system]; Mental retardation, mild

PRENATAL MANIFESTATIONS: [Amniotic fluid]; Oligohydramnios