We found 34 diseases and 77 genes matching your search

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Filippi syndrome

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

Filippi syndrome

Filippi syndrome is an extremely rare genetic condition characterized by a small head (microcephaly), webbing of the fingers and toes (syndactyly), intellectual disability, growth delay, and distinctive facial features (high and broad nasal bridge, thin nostrils, small chin or micrognathia, and a high frontal hairline). Other features can include undescended testicles in males, extra fingers (polydactyly), as well as teeth and hair abnormalities. So far, less than 25 cases have been reported in the medical literature. This condition is inherited in an autosomal recessive fashion. The exact underlying genetic cause is not known
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Filippi syndrome

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

Filippi syndrome is characterised by microcephaly, cutaneous syndactyly of the fingers and toes, intellectual deficit, growth retardation and a characteristic facies (high and broad nasal bridge, thin alae nasi, micrognathia and a high frontal hairline). So far, less than 25 cases have been reported. Cryptorchidism, polydactyly, and teeth and hair anomalies may also be present. Transmission is autosomal recessive. Last update: April 2008
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Filippi syndrome

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

Description

A number sign (#) is used with this entry because of evidence that Filippi syndrome (FLPIS) is caused by homozygous or compound heterozygous mutation in the CKAP2L gene (616174) on chromosome 2q13.Filippi syndrome is characterized by short stature, microcephaly, syndactyly, intellectual disability, and facial dysmorphism consisting of bulging forehead, broad and prominent nasal bridge, and diminished alar flare. Common features include cryptorchidism, speech impairment, and clinodactyly of the fifth finger, Some patients exhibit visual disturbances, polydactyly, seizures, and/or ectodermal abnormalities, such as nail hypoplasia, long eyelashes, hirsutism, and microdontia (summary by Hussain et al., 2014).

Clinical features

Scott et al. (1971) described a craniodigital syndrome with mental retardation in 3 brothers. The mother and the maternal grandmother had soft tissue syndactyly between toes 2 and 3. The father and mother were 46 and 31 years old, respectively, at the birth of their first child. Somatic and mental development was delayed. From birth the facies were abnormal with brachycephaly, small and narrow nose, 'startled' appearance, thick head hair with extension of the hair unusually far on the temples and sideburn areas, long eyelashes, thick eyebrows, and somewhat short mandible. The digital anomalies were soft-tissue syndactyly between toes 2 and 3 and between fingers 2, 3, and 4. The der...

Symptoms

INHERITANCE: Autosomal recessive

GROWTH: [Weight]; Low weight; [Other]; Intrauterine growth retardation; Postnatal growth retardation

HEAD AND NECK: [Head]; Microcephaly; [Face]; Broad forehead; Hairy forehead; Short philtrum; [Eyes]; Poor vision; Retrobulbar venous varix; Proptosis; Optic atrophy; [Nose]; Prominent columella; Broad nasal bridge; Hypoplastic alae nasi; [Mouth]; Straight mouth; Thin lips; [Teeth]; Small teeth; Abnormally shaped teeth; Hypodontia (rare); Serrated incisors (rare)

CARDIOVASCULAR: [Heart]; Ventricular septal defect; [Vascular]; Retrobulbar venous varix

GENITOURINARY: [Internal genitalia, male]; Cryptorchidism; Ambiguous genitalia (rare)

SKELETAL: [Skull]; Microcephaly; [Hands]; Bilateral cutaneous syndactyly of third and fourth fingers; Fifth-finger clinodactyly; [Feet]; Bilateral cutaneous syndactyly of second, third, and fourth toes; Hypoplasia of fifth toes (in some patients)

SKIN, NAILS, HAIR: [Hair]; Abnormal hair growth pattern; Sparse hair (rare); Hypertrichosis (rare)

NEUROLOGIC: [Central nervous system]; Mental retardation; Seizures; Dystonic movements; Dystonic tongue protrusion; Cerebellar atrophy; Arachnoidal cyst; Diffuse enlargement of subarachnoid spaces and lateral ventricles (rare); Megacisterna magna (rare)

MOLECULAR BASIS: Caused by mutation in the cytoskeleton-associated protein 2-like gene (CKAP2L, 616174.0001)
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Microcephaly - intellectual disability - phalangeal and neurological anomalies

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

This syndrome is characterised by microcephaly, severe intellectual deficit, phalangeal anomalies (cutaneous syndactyly of the fingers, toe brachyclinodactyly and nail hypoplasia) and neurological manifestations (epilepsy, spastic/dystonic paraplegia and brisk reflexes). So far, it has been described in three children born to a consanguineous couple of Pakistani origin. Hypotonia, pre- and postnatal growth retardation, a characteristic face (broad forehead with a low frontal hair line, a broad nasal bridge and prominent columella, hypoplastic alae nasi, short philtrum, and a straight mouth with thin lips and downward slanting palpebral fissures) and optic atrophy were also reported. Autosomal recessive inheritance is likely. Last update: April 2008
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Woods syndrome

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

Clinical features

Among the children of a Pakistani couple related as first cousins, Woods et al. (1992) observed a distinctive nonprogressive disorder characterized by variable phalangeal anomalies, microcephaly, pre- and postnatal growth retardation, poor vision, dystonic movements, characteristic face, and severe mental retardation. Three children, 2 girls and a boy, were affected. The 2 girls had bilateral complete cutaneous syndactyly of the third and fourth fingers; the boy had bilateral single palmar creases. All 3 children showed dystonic tongue movements with tongue protrusion. One of the children had an asymptomatic ventricular septal defect and the same child developed a venous varix behind the right eye, causing proptosis and occasional subluxation of the eye, during the second year. She had bilateral optic atrophy. The second sister also showed optic atrophy; ophthalmoscopy was not performed in the brother. The facies were described as showing broad and hairy forehead, broad nasal bridge, prominent columella, relatively hypoplastic alae nasi, short philtrum, and a straight mouth with thin lips. Woods et al. (1992) concluded that the condition in their family was different from Filippi syndrome (272440) because the facial appearances were different and children with Filippi syndrome do not have localizing neurologic signs.

For a similar craniofacial syndrome, see 251255.

Inheritance

Consanguinity in the family reported by Woods et al. (1992) suggested autosomal recessive inheritance of the disorder.
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Mental retardation and microcephaly with pontine and cerebellar hypoplasia

Retrieved: 27-07-2015
Source: WIKIPEDIA (Original article)
Associated genes: cask
Mental retardation and microcephaly with pontine and cerebellar hypoplasia (MICPCH), also known as Mental retardation, X-linked, syndromic, Najm type (MRXSNA), is a rare genetic disorder of infants characterised by intellectual disability and pontocerebellar hypoplasia. The disorder is associated with a mutation in the CASK gene which is transmitted in an X-linked manner. As with the vast majority of genetic disorders, there is no known cure to MICPCH.

See also

Pontocerebellar hypoplasia X-linked mental retardation
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X-linked intellectual disability, Najm type

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

Najm type X-linked intellectual deficit is a rare cerebellar dysgenesis syndrome characterized by variable clinical manifestations ranging from mild intellectual deficit with or without congenital nystagmus, to severe cognitive impairment associated with cerebellar and pontine hypoplasia/atrophy and abnormalities of cortical development. Prevalence of this rare neurological syndrome is unknown. Up to 35 families have been reported to date. Patients (mostly females) have been reported to have variable clinical manifestations including intellectual deficit, severe developmental delay, seizures, unsteady gait, sensorineural hearing loss and postnatal microcephaly (in most cases). Minor facial anomalies include: low or broad forehead, hypertelorism, long philtrum and micrognathia. Ocular findings are also variable and include congenital nystagmus, strabismus, cataracts, myopia or reduced visual acuity. Males appear to be more severely affected. Point mutations and deletions in the CASK gene (Xp11.4) have been found in patients with this syndrome. Magnetic resonance imaging (MRI) generally shows pontocerebellar hypoplasia/atrophy and simplified cortical gyri. Molecular genetic testing is needed to confirm diagnosis. Transmission follows an X-linked dominant pattern. Expert reviewer(s) Dr Ginevra ZANNI Last update: February 2013
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Mental retardation and microcephaly with pontine and cerebellar hypoplasia

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

Description

A number sign (#) is used with this entry because of evidence that the MICPCH syndrome is caused by heterozygous mutation or deletion in the CASK gene (300172) on chromosome Xp11.

Missense variants in the CASK gene have been shown to cause a milder mental retardation syndrome, sometimes including nystagmus, most often in males (FGS4; 300422).Mental retardation and microcephaly with pontine and cerebellar hypoplasia (MICPCH) is an X-linked disorder affecting females and characterized by severe intellectual disability, microcephaly, and variable degrees of pontocerebellar hypoplasia. Affected individuals have very poor psychomotor development, often without independent ambulation or speech, and axial hypotonia with or without hypertonia. Some may have sensorineural hearing loss or eye anomalies. Dysmorphic features include overall poor growth, severe microcephaly (-3.5 to -10 SD), broad nasal bridge and tip, large ears, long philtrum, micrognathia, and hypertelorism (summary by Moog et al., 2011).

Clinical features

Najm et al. (2008) reported several patients with a phenotype of congenital and marked postnatal microcephaly, severe mental retardation, and disproportionate pontine and cerebellar hypoplasia. Four were female and 1 was male. The first girl was referred at 4 years of age because of congenital and marked postnatal microcephaly, severe mental retardation, and sensorineural hearing loss. Her brain MRI showed re...

Symptoms

INHERITANCE: X-linked dominant

GROWTH: [Height]; Short stature; [Weight]; Low weight; [Other]; Growth retardation, postnatal

HEAD AND NECK: [Head]; Microcephaly, progressive (-3.5 to -10 SD); [Face]; Oval face; Long philtrum; Micrognathia; [Ears]; Large ears; Hearing loss, sensorineural (less common); [Eyes]; Large eyes; Hypertelorism, mild; Epicanthal folds; Optic nerve hypoplasia (less common); Optic disc pallor (less common); Strabismus (less common); Nystagmus (less common); [Nose]; Broad nasal bridge; Prominent nasal bridge; Broad nasal tip; Small nose; [Mouth]; High-arched palate

SKELETAL: [Spine]; Scoliosis (less common)

SKIN, HAIR, NAILS: [Skin]; Hypohidrosis

MUSCLE, SOFT TISSUE: Hypotonia; Muscle weakness

NEUROLOGIC: [Central nervous system]; Delayed psychomotor development; Mental retardation, moderate to severe; Most never acquire independent ambulation; Lack of speech development; Axial hypotonia; Peripheral hypertonia; Spasticity; Hyperreflexia; Seizures (less common); Hyposensitivity to pain (less common); Proportionate pontocerebellar hypoplasia seen on MRI; Dilated fourth ventricle; Simplified gyration in the frontal cortex (less common)

MISCELLANEOUS: Onset at birth or early infancy; Dysmorphic facial features are variable

MOLECULAR BASIS: Caused by mutation in the calcium/calmodulin-dependent serine protein kinase gene (CASK, 300172.0001)

Carnevale syndrome

Retrieved: 27-07-2015
Source: Orphanet (Original article)
Associated genes: colec11, masp1

This disease has been moved to Craniofacial-ulnar-renal syndrome

3mc syndrome 2

Retrieved: 27-07-2015
Source: OMIM (Original article)
Associated genes: colec11, masp1

Description

A number sign (#) is used with this entry because of evidence that 3MC syndrome-2 is caused by homozygous mutation in the COLEC11 gene (612502) on chromosome 2p25.The term '3MC syndrome' encompasses 4 rare autosomal recessive disorders that were previously designated the Carnevale, Mingarelli, Malpuech, and Michels syndromes, respectively. The main features of these syndromes are facial dysmorphism that includes hypertelorism, blepharophimosis, blepharoptosis, and highly arched eyebrows, which are present in 70% to 95% of cases. Cleft lip and palate, postnatal growth deficiency, cognitive impairment, and hearing loss are also consistent findings, occurring in 40% to 68% of cases. Craniosynostosis, radioulnar synostosis, and genital and vesicorenal anomalies occur in 20% to 30% of cases. Rare features include anterior chamber defects, cardiac anomalies, caudal appendage, umbilical hernia (omphalocele), and diastasis recti (summary by Rooryck et al., 2011).

For a discussion of genetic heterogeneity of 3MC syndrome, see 3MC1 (257920).

Clinical features

Carnevale et al. (1989) described 2 sons of consanguineous parents with an apparently distinct syndrome manifested by eyelid ptosis, convergent strabismus, partial agenesis of the abdominal muscles, hip dislocation, cryptorchidism, and developmental delay. The elbows showed an ability to extend fully with limitation of pronation and supination. In addition to blepharoptosis, the brothers had blepharophimosis and epicanthus inversus as in the autosomal dominant disorder of blepharophimosis (110100).

Guion-Almeida and Rodini (1995) reported a Brazilian girl born of first-cousin parents and presenting with craniosynostosis, telecanthus, blepharophimosis, blepharoptosis, epicanthus inversus, cleft lip and palate, skeletal defects, and hearing loss. She did not have mental retardation.

...

Symptoms

INHERITANCE: Autosomal recessive

GROWTH: [Other]; Postnatal growth retardation

HEAD AND NECK: [Head]; Asymmetric head; [Face]; Broad forehead; Broad philtrum; Prominent premaxilla; [Ears]; Hearing loss (rare); [Eyes]; Hypertelorism; Highly arched eyebrows; Downward slanted palpebral fissures; Ptosis; Strabismus; Eversion of the lower eyelids; Blepharophimosis; [Nose]; High nasal bridge; Broad nasal bridge; Broad, flat nasal tip; [Mouth]; Cleft lip; Cleft palate; Downturned corners of the mouth; [Neck]; Torticollis

ABDOMEN: [External features]; Umbilical depression

SKELETAL: Joint hypermobility; [Skull]; Craniosynostosis; Asymmetric skull; [Spine]; Vertebral anomalies; [Limbs]; Limited elbow mobility; Radioulnar synostosis (in some patients)

MUSCLE, SOFT TISSUE: Diastasis recti; Abdominal muscle hypoplasia; Umbilical depression

NEUROLOGIC: [Central nervous system]; Mental retardation (rare)

MOLECULAR BASIS: Caused by mutation in the collectin 11 gene (612502.0001)
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Simosa craniofacial syndrome

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

Clinical features

Simosa et al. (1989) described the cases of a mother and son with high forehead, elongated and flattened face, arched and sparse eyebrows, short palpebral fissures, telecanthus, long nose and hypoplastic nostrils, long philtrum, microstomia, high and narrow palate, nasal speech, chin dimples, and a highly unusual bilateral auricular malformation. Intelligence and hearing were normal. Although to some extent the facies suggested the 'whistling face' syndrome (193700), it appeared to be a distinct entity.

Symptoms

INHERITANCE: Autosomal dominant

HEAD AND NECK: [Face]; Flat facies; Long face; Long philtrum; Chin dimples; Broad forehead; [Ears]; Normal hearing; Low-set ears; Posteriorly rotated ears; Auricular malformation; [Eyes]; Arched, sparse eyebrows; Telecanthus; Blepharophimosis; [Nose]; Long nose; Hypoplastic nostrils; Broad nasal bridge; Flattened nasal tip; [Mouth]; Microstomia; High, narrow palate

GENITOURINARY: [External genitalia, male]; Inguinal hernia

SKIN, NAILS, HAIR: [Skin]; Chin dimples; [Hair]; Arched, sparse eyebrows

VOICE: Nasal speech
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Trisomy 22

Retrieved: 27-07-2015
Source: GARD (Original article)
Associated genes: cd6, kit, myh11, flt3

Trisomy 22

Trisomy 22 is a chromosome disorder in which an extra (third) copy of chromosome 22 is present in every cell of the body where there should normally only be two copies. This condition is commonly found in miscarriages, but only rarely in liveborn infants. Most affected individuals die shortly before or shortly after birth due to severe complications. Common features include an underdeveloped midface (midface hypoplasia) with flat/broad nasal bridge, malformed ears with pits or tags, cleft palate, hypertelorism (wide-spaced eyes), microcephaly and other cranial abnormalities, congenital heart disease, genital abnormalities, and intrauterine growth restriction (IUGR)
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Nasopalpebral lipoma - coloboma - telecanthus

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

This syndrome is characterized by nasopalpebral lipomas, bilateral lid coloboma, and telecanthus. It has been described in less than 30 patients. Other manifestations may include maxillary hypoplasia, hypertelorism, and dysmorphic features. It is transmitted as an autosomal dominant trait with complete penetrance. Surgery can be performed to repair the eyelid coloboma and remove the bilateral nasopalpebral lipomas. Last update: December 2006
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Palpebral coloboma-lipoma syndrome

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

Description

Nasopalpebral lipoma-coloboma syndrome is an autosomal dominant condition characterized by upper eyelid and nasopalpebral lipomas, colobomas of upper and lower eyelids, telecanthus, and maxillary hypoplasia (summary by Suresh et al., 2011).

Clinical features

Penchaszadeh et al. (1980, 1982) described a Venezuelan family in which 8 persons in 3 generations showed bilateral coloboma of the upper and lower lids at the junction between their middle and inner thirds; prominent circumscribed, rounded deposits of fat in the medial region of both upper lids; aplasia or malposition of the lacrimal puncta; ocular hypertelorism; broad nasal bridge and fatty accumulations on the nasal bridge and nasolabial areas. Male-to-male transmission was observed. Penetrance appeared to be complete. One affected male in the second generation had affected children by each of 2 wives and only normal children by a third.

This syndrome was validated by the Turkish family reported by Akarsu and Sayli (1991) in which 7 members in 4 generations were affected. Features included congenital nasopalpebral lipoma, telecanthus, and bilateral colobomas of upper and lower lids without midface hypoplasia. The family contained 2 instances of male-to-male transmission. The appearance as pictured from both the Venezuelan and the Turkish family was striking. The syndrome is easily distinguished from frontonasal dysplasia (136760) and from craniofrontonasal dysplasia (304110), which it only superficially resembles.

Bock-Kunz et al. (2000) described the ophthalmic manifestations and clinical course of a newborn with nasopalpebral lipoma-coloboma syndrome. In addition to the ocular and maxillofacial findings described in the existing literature, the patient had small amplitude jerk nystagmus with a latent component, high hyperopic astigmatism, and variable, intermittent exotropia which resolved with part-time occlusion of the preferred eye. Surgery was performed to repair the bilateral upper eyelid coloboma and remove the bilateral nasopalpebral lipomata. Cytogenetic studies revealed no evidence of chromosomal abnormality, and the authors concluded that the patient's craniofacial dysmorphism had resulted from a spontaneous mutation.

Suresh et al. (2011) described a sporadic case of nasopalpebral lipoma-coloboma syndrome in a 16-year-old Indian girl, born of nonconsanguineous parents. In addition to the typical features of the disorder, she had a limbal dermoid.

Inheritance

The transmission pattern of the disorder in the families reported by Penchaszadeh et al. (1982) and Akarsu and Sayli (1991) was consistent with autosomal dominant inheritance with complete penetrance.

Symptoms

Eyes: Coloboma of upper and lower eyelids; Lipomas of upper lids; Aplasia or malposition of lacrimal puncta; Ocular hypertelorism

Nose: Broad nasal bridge; Lipomas of nasal bridge and nasolabial areas

Inheritance: Autosomal dominant

Primordial short stature - microdontia - opalescent and rootless teeth

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

This disease has been moved to Microcephalic osteodysplastic primordial dwarfism type II

Aarskog-Scott syndrome

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

Aarskog-Scott syndrome (AAS) is a rare developmental disorder characterized by facial, limbs and genital features, and a disproportionate acromelic short stature. AAS prevalence is not known, but less than 100 cases have been reported in the literature since the first description in 1970. However, prevalence estimates are thought to be around 1/25,000. About 40 molecularly proven cases are published worldwide. AAS predominantly concerns males. Facial features include widow's peak and hypertelorism, both observed in female carriers, and downslanting palpebral fissures, broad nasal bridge, anteversed nostrils, low set and protuberant ears, maxillary hypoplasia and transverse crease below the lower lip. AAS patients have short and broad hands and feet, interdigital webbing, clinodactyly, and hyperextension of proximal interphalangeal joints and flexion at distal interphalangeal joints causing swan neck deformity of fingers. Size is generally normal at birth, but growth is slow in infancy and childhood, leading to short stature until puberty, which is often delayed. A growth spurt in late teens, generally, results in a moderate short stature. Genital anomalies may include cryptorchidism, macroorchidism, shawl scrotum and, more rarely, hypospadias. Fertility is normal. Female carriers may have only a subtle phenotype with hypertelorism and widow's peak. Patients may present a neurodevelopmental phenotype with learning and behavioural disabilities that are often confined to early childhood. When present, mental impairment is rarely severe. Although clinically and genetically heterogeneous, the best characterized form of the disorder is caused by mutations in the FGD1 gene (faciogenital dysplasia 1 gene; Xp11.21). Other gene(s) might be involved since most familial cases still do not have identified genetic cause. Clinical diagnosis is based on physical examination and the recognition of the most distinctive clinical hallmarks. Molecular genetics, based on analysi...

Helsmoortel-van der aa syndrome

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

Clinical features

A number sign (#) is used with this entry because of evidence that Helsmoortel-Van der Aa syndrome (HVDAS) is caused by heterozygous mutation in the ADNP gene (611386) on chromosome 20q13.Helsmoortel et al. (2014) reported 10 unrelated children with intellectual disability, autism spectrum disorder, and dysmorphic facial features. The patients were ascertained from several large cohorts of individuals with similar features. Nine of the 10 patients had developmental delay apparent in infancy, and 5 of the patients had severe intellectual disability in childhood, with some being nonverbal. Neuropsychiatric features were relatively common, including attention deficit/hyperactivity disorder, anxiety disorder, obsessive compulsive behavior, and stereotypic behaviors. Other frequent findings included hypotonia, feeding problems in infancy, recurrent infections, short stature, joint laxity, and hand abnormalities. Two patients had seizures and 3 had a congenital heart defect. Dysmorphic features varied, but included prominent forehead, high hairline, downslanting palpebral fissures, notched eyelids, broad nasal bridge, thin upper lip, and smooth philtrum.

Pescosolido et al. (2014) reported a 6-year-old girl with HVDAS who presented in infancy with hypotonia, multiple cyanotic episodes thought to be due to breath holding, and feeding difficulties. She showed global developmental delay with delayed language, attention deficit-hyperactivity disorder, a nonspecific mood disorder, and autistic features. Dysmorphic features included broad forehead and slightly tented lips. She also had visual problems, including hypermetropia, cortical visual impairment, exotropia, mild amblyopia, and astigmatism. Treatment resulted in significant improvement in her...

Symptoms

INHERITANCE: Autosomal dominant

GROWTH: [Height]; Short stature; [Weight]; Obesity

HEAD AND NECK: [Head]; Prominent forehead; [Face]; Smooth philtrum; [Eyes]; Downslanting palpebral fissures; Notched eyelid; Ptosis; Strabismus; Hypermetropia; Visual impairment; [Nose]; Broad nasal bridge; Short nose; [Mouth]; Thin upper lip

CARDIOVASCULAR: [Heart]; Congenital heart defect (less common)

ABDOMEN: [Gastrointestinal]; Feeding difficulties

SKELETAL: Joint laxity; [Hands]; Small hands

MUSCLE, SOFT TISSUE: Hypotonia

NEUROLOGIC: [Central nervous system]; Delayed psychomotor development; Developmental delay apparent in infancy; Intellectual disability, mild to severe; Language impairment; Seizures (less common); [Behavioral/psychiatric manifestations]; Autism spectrum disorder; Obsessive-compulsive behavior; Stereotypic behavior; Hyperactivity

IMMUNOLOGY: Recurrent infections

MISCELLANEOUS: Onset in infancy; Variable extraneurologic features

MOLECULAR BASIS: Caused by mutation in the activity-dependent neuroprotector homeobox gene (ADNP, 611386.0001)
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Rhizomelic chondrodysplasia punctata type 2

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

This disease is described under Rhizomelic chondrodysplasia punctata
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Microcephaly, corpus callosum dysgenesis, and cleft lip/palate

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

Clinical features

Tutuncuoglu et al. (1996) described a 46,XY Turkish male infant with microcephaly, severe hypoplasia of the corpus callosum, exophthalmos, cleft lip and palate, seizures, and psychomotor retardation. His parents were first cousins. A similar case was reported by Howard and Young (1988), but their patient also had preaxial polydactyly. Marles and Chudley (1990) described similar findings in a 9-month-old boy: failure to thrive, developmental delay, bilateral cleft lip and palate, and left preaxial polydactyly. The boy had a broad nasal bridge and bilateral epicanthic folds. A right inguinal hernia was repaired surgically. The parents were not related.

Inheritance

Tutuncuoglu et al. (1996) suggested that this condition may be an autosomal recessive disorder.

Symptoms

Head: Microcephaly

Neuro: Hypoplasia of corpus callosum; Seizures; Psychomotor retardation

Eyes: Exophthalmos

Mouth: Cleft lip/palate

Limbs: Preaxial polydactyly

Inheritance: Autosomal recessive
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Pallister w syndrome

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

Description

Pallister et al. (1974) described 2 brothers with a mental retardation syndrome characterized by an unusual physiognomy (frontal prominence), anterior cowlick, hypertelorism, antimongoloid orbital slant, and broad, flat nasal bridge like that of the OPD syndrome (311300), midline notch of upper lip and submucous cleft of the hard palate, absent upper central incisors, limited motion at the elbow due to subluxation, camptodactyly, and pes cavus. In addition to the mental retardation, the patients had grand mal seizures. The mother and a sister were considered mildly affected, consistent with heterozygous manifestation of an X-linked trait. Bottani and Schinzel (1993) described a patient thought to have this disorder. Severe mental retardation with seizures was associated with a pattern of facial dysmorphism, including high broad forehead, downslanting palpebral fissures, hypertelorism, peculiar nose, and peculiar upper lip with a median notch (incomplete midline oral cleft). The face was compared to that of a boxer, i.e., pugilistic face.

Goizet et al. (1999) reported 3 patients with the Pallister W syndrome and reviewed the 4 patients in 2 separate families that had previously been described. Constant features seemed to be characteristic facies with prominent mandible and pugilistic appearance, and central nervous system involvement with strabismus, spasticity, and moderate to severe mental retardation.

Symptoms

Neuro: Mental retardation; Seizures; Mild spasticity

Facies: Frontal prominence

Eyes: Hypertelorism; Telecanthus; Down-slanting palpebral fissures; Alternating esotropia

Nose: Broad nasal bridge; Flat nasal bridge Broad nasal tip

Mouth: Midline notch of upper lip; Submucous cleft hard palate; Broad uvula

Teeth: Absent upper central incisors

Hair: Anterior cowlick

Joints: Limited elbow motion due to subluxation

Limbs: Cubitus valgus; Short ulna; Bowed radius; Camptodactyly; Clinodactyly; Pes cavus; Metatarsus varus; Pes planus

Inheritance: X-linked
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W syndrome

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

W syndrome is characterised by intellectual deficit, epileptic seizures and facial dysmorphism. Skeletal anomalies are also often present. To date, it has been described in six male patients. The mode of transmission appears to be X-linked dominant. Last update: October 2006
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Smith-Magenis syndrome

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

Smith-Magenis syndrome

El síndrome de Smith-Magenis es un trastorno genético que afecta muchos órganos y sistemas del cuerpo y que se debe a una delección (pérdida) de material genético en una región especifica del cromosoma 17.Aunque esta región contiene varios genes, los investigadores creen que esta asociada con la pérdida de un gen particular, RAI1. La mayoría de los casos no se heredan. Se caracteriza por un atraso intelectual moderado, atraso en el lenguaje y algunas características del rostro que son distintivas. El tratamiento es de apoyo
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Smith-Magenis syndrome

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

Smith-Magenis syndrome (SMS) is a complex genetic disorder characterized by variable intellectual deficit, sleep disturbance, craniofacial and skeletal anomalies, psychiatric disorders, and speech and motor delay. SMS has an estimated prevalence of 1/15,000-25,000 and has been identified worldwide in all ethnic groups, but is probably underdiagnosed. Males and females are affected equally. Patients have a recognizable clinical picture. Craniofacial features include brachycephaly, frontal bossing, hypertelorism, synophrys, upslanting palpebral fissures, midface hypoplasia, a broad square-shaped face with depressed nasal bridge, an everted upper lip with a ``tented'' appearance, and micrognathia in infancy. Dental anomalies include tooth agenesis and taurodontism. Short stature is common in young patients, with height typically in the normal range as adults. Excess weight and/or obesity in teens and adults are common. Other skeletal anomalies include brachydactyly, scoliosis, 5th-finger clinodactyly, 2/3 toe syndactyly, forearm and elbow limitations, vertebral anomalies, persistent fetal finger pads, and polydactyly. Otolaryngological problems such as velopharyngeal insufficiency, a hoarse deep voice, and vocal cord nodules and polyps are also common; hearing loss (60% of patients) is variable and may be mild to moderate. Ophthalmologic features (>60%) include myopia and iris anomalies and rarely, retinal detachment (often resulting from violent behaviors). Mild to moderate intellectual deficit, significant speech delay, decreased sensitivity to pain, peripheral neuropathy, as well as characteristic sleep disturbances and maladaptive behaviors (outbursts/temper tantrums, attention seeking, aggression, disobedience, distraction, and self-injurious behaviors) are common. Organ malformations (30-40%) include cardiac, renal, urinary tract, and central nervous system (CNS) abnormalities. SMS is typically a sporadic disorder caused either by a 17p11.2 deletion e...
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Smith-Magenis syndrome

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

What is Smith-Magenis syndrome?

Smith-Magenis syndrome is a developmental disorder that affects many parts of the body. The major features of this condition include mild to moderate intellectual disability, delayed speech and language skills, distinctive facial features, sleep disturbances, and behavioral problems. Most people with Smith-Magenis syndrome have a broad, square-shaped face with deep-set eyes, full cheeks, and a prominent lower jaw. The middle of the face and the bridge of the nose often appear flattened. The mouth tends to turn downward with a full, outward-curving upper lip. These facial differences can be subtle in early childhood, but they usually become more distinctive in later childhood and adulthood. Dental abnormalities are also common in affected individuals. Disrupted sleep patterns are characteristic of Smith-Magenis syndrome, typically beginning early in life. Affected people may be very sleepy during the day, but they have trouble falling asleep and awaken several times each night. People with Smith-Magenis syndrome have affectionate, engaging personalities, but most also have behavioral problems. These include frequent temper tantrums and outbursts, aggression, anxiety, impulsiveness, and difficulty paying attention. Self-injury, including biting, hitting, head banging, and skin picking, is very common. Repetitive self-hugging is a behavioral trait that may be unique to Smith-Magenis syndrome. People with this condition also compulsively lick their fingers and flip pages of books and magazines (a behavior known as "lick and flip"). Other signs and symptoms of Smith-Magenis syndrome include short stature, abnormal curvature of the spine (scoliosis), reduced sensitivity to pain and temperature, and a hoarse voice. Some people with this disorder have ear abnormalities that lead to hearing loss. Affected individuals may have eye abnormalities that cause nearsightedness (myopia) and other vision problems. Although less common, he...

Keywords

Smith-Magenis syndrome,Chromosome Disorders,Genetic Diseases, Inborn,Congenital Abnormalities,Chronobiology Disorders,Congenital, Hereditary, and Neonatal Diseases and Abnormalities,Nervous System Diseases,Abnormalities, Multiple,Smith-Magenis Syndrome,Bones, muscles, and connective tissues,Brain and nervous system,Mental health and behavior,contiguous gene deletion syndrome,del 17p11.2,del(17)(p11.2),microdeletion,RAI1,RAI1 gene,17p11.2 monosomy,17p- syndrome,chromosome 17p deletion syndrome,deletion 17p syndrome,partial monosomy 17p,SMS,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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Alpha-thalassemia/mental retardation syndrome, chromosome 16-related

Retrieved: 27-07-2015
Source: OMIM (Original article)
Associated genes: cyp11b2, hbhr, hba2, hba1

Clinical features

A number sign (#) is used with this entry because of evidence that the disorder represents a contiguous gene syndrome due to a deletion in chromosome 16p that involves the alpha-1 (HBA1; 141800) and alpha-2 (HBA2; 141850) genes, among others.

X-linked alpha-thalassemia/mental retardation syndrome (ATR-X; 301040) is a similar phenotypic disorder caused by mutation in the ATRX gene (300032).Weatherall et al. (1981) reported the association of hemoglobin H disease (Hb H; see alpha-thalassemias, 141800) and mental retardation in 3 unrelated patients of northern European descent.

Hjelle et al. (1982) described a somewhat similar case in a male of northern European extraction. Hb H was associated with multiple congenital anomalies: spina bifida from T6 to the sacrum with a T10-L4 myelomeningocele, congenital cataracts, bilateral inguinal hernias, bilateral deformities of the femoral necks, and subluxation of the left hip. One of his 2 sibs also had congenital cataracts, but there was no family history of other congenital anomalies or of fetal wastage. According to restriction enzyme analyses, the father had 2 alpha-globin genes on one chromosome and only 1 gene on the homolog (i.e., was a silent alpha-thalassemia carrier), whereas the mother had cis alpha-thalassemia trait (i.e., 2 alpha genes on 1 chromosome and none on the homolog). T...

Symptoms

INHERITANCE: Autosomal dominant

GROWTH: [Height]; Short stature; [Weight]; Obesity, mild (less common)

HEAD AND NECK: [Head]; Microcephaly; [Face]; Wide, flat, broad forehead; Long philtrum; Retrognathia, mild; [Ears]; Small ears; [Eyes]; Epicanthal folds; Hypertelorism; Downslanting palpebral fissures; Ptosis; [Nose]; Flat, broad nasal bridge; Triangular nasal tip; Anteverted nostrils; [Mouth]; High-arched palate; Protruding tongue; [Teeth]; Crowded teeth; [Neck]; Short neck; Webbed neck

CARDIOVASCULAR: [Vascular]; Patent ductus arteriosus (in 1 reported case)

CHEST: [External features]; Asymmetric chest; [Breasts]; Abnormally placed nipples; Accessory nipple

GENITOURINARY: [External genitalia, male]; Micropenis; Hypospadias; [Internal genitalia, male]; Cryptorchidism

SKELETAL: [Hands]; Clinodactyly of isolated digits; [Feet]; Talipes equinovarus

NEUROLOGIC: [Central nervous system]; Mental retardation, mild to moderate; Seizures (less common)

HEMATOLOGY: Alpha-thalassemia; Microcytic, hypochromic anemia; Hb H inclusions in red blood cells

LABORATORY ABNORMALITIES: Subtelomeric deletion of chromosome 16p; Normal serum ferritin

MISCELLANEOUS: Highly variable phenotype; See also X-linked alpha-thalassemia/mental retardation syndrome (301040); Contiguous gene syndrome

MOLECULAR BASIS: A contiguous gene syndrome caused by deletion of the alpha-1 hemoglobin (141800) and alpha-2 hemoglobin (141850) genes
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Hypertelorism - hypospadias - polysyndactyly syndrome

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

Hypertelorism-hypospadias-polysyndactyly syndrome is a very rare syndrome associating an acro-fronto-facio-nasal dysostosis with genitourinary anomalies. It has been described in three families. Craniofacial manifestations include wide anterior fontanel, flat occiput, hypertelorism, ptosis, proptosis, broad nasal bridge and nasal tip, long philtrum and posteriorly rotated or low set ears. Hypospadias and shawl scrotum are present in all males. Acral manifestations include syndactyly of fingers, broad thumbs or halluces or preaxial polydactyly. The affected patients have no intellectual deficit. The condition seems to be hereditary, and transmitted as an autosomal recessive trait. Last update: October 2010

Digitorenocerebral syndrome

Retrieved: 27-07-2015
Source: Orphanet (Original article)
Associated genes: tbc1d24

Deafness onychodystrophy osteodystrophy and mental retardation syndrome

Retrieved: 27-07-2015
Source: GARD (Original article)
Associated genes: tbc1d24

Deafness onychodystrophy osteodystrophy and mental retardation syndrome

Deafness onychodystrophy osteodystrophy and mental retardation (DOOR) syndrome is a rare genetic disorder that is usually recognized shortly after birth. The term DOOR is an acronym with each letter representing a common feature in affected individuals: (D)eafness due to a defect of the inner ear or auditory nerve; (O)nychodystrophy or malformation of the nails; (O)steodystrophy, meaning malformation of certain bones; and mild to profound mental (R)etardation, which is now referred to as intellectual disability. In some cases, individuals may also experience seizures. This condition is inherited in an autosomal recessive fashion; the exact genetic cause is unknown
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CLN10 disease

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

This disease is described under Neuronal ceroid lipofuscinosis
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Mental retardation, autosomal dominant 18

Retrieved: 27-07-2015
Source: OMIM (Original article)
Associated genes: gatad2b

Clinical features

A number sign (#) is used with this entry because this form of mental retardation (MRD18) is caused by heterozygous mutation in the GATAD2B gene (614998) on chromosome 1q23.De Ligt et al. (2012) reported a girl (patient 69) with global developmental delay who learned to walk at 3 years and had a few single words at age 8. She had tics, high pain threshold, and hypoplasia of the optic nerve. At 34 years of age, she had severe intellectual disability and strabismus and made grimaces. Height and head circumference were normal. Facial characteristics included thin blonde hair, deeply set eyes, tubular nose with a broad nasal tip, and a large mouth with a thin upper lip. The woman was found to have a mutation in the GATAD2B gene. De Ligt et al. (2012) screened a second cohort of 765 individuals with intellectual disability and identified a second mutation in GATAD2B in a patient with severe developmental delay with delayed motor milestones, limited speech, and overlapping facial features.

Willemsen et al. (2013) reported a girl with developmental delay and similar dysmorphic features as the patients reported by de Ligt et al. (2012). The patient was hypotonic in the neonatal period and thereafter showed delayed psychomotor development. She learned to walk at age 2 years and started to speak during the third year, but only spoke 6 words at age 12 years. Her behavior was characterized by hyperactivity, inappropriate laughter, obsession for shiny objects, and mild self-mutilation. She also had strabismus and hypermetropic astigmatism. Facial dysmorphism included a broad forehead, a broad nasal bridge with full nose tip, a broad mouth with wide-spaced central incisors, short philtrum, and long palpebral fissures. She had thin, blond hair. Her fingers were long and she had fleshy hands.

Cytogenetics

Willemsen et al. (2013) reported a girl with intellectual disability associated with a de novo heterozygous 249-kb deletion of chromosome 1q21.3 encompassing 10 genes and disrupting GATAD2B. No other known disease-related genes were in the deleted region. The girl had hypotonia and feeding difficulties in the neonatal period, followed by delayed psychomotor development and poor speech. Medical problems included hypermetropia and strabismus, and she had 1 episode of absence epilepsy. Facial dysmorphism included hypertelorism, a broad forehead, a broad and flat nasal bridge, and a full square tip of the nose. She had thin, blond hair.

Molecular genetics

In 2 patients with severe intellectual disability and similar dysmorphic features, de Ligt et al. (2012) identified heterozygous de novo mutations in the GATAD2B gene: a nonsense mutation (Q470X; 614998.0001) and a frameshift mutation (614998.0002).

In a patient with intellectual disability and dysmorphic features, Willemsen et al. (2013) identified a heterozygous truncating mutation in the GATAD2B gene (614998.0003). Her unaffected mother carried the mutation in mosaic state (10% in peripheral blood leukocytes). ...
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Hyperphosphatasia with mental retardation syndrome 4

Retrieved: 27-07-2015
Source: OMIM (Original article)
Associated genes: pgap3

Description

A number sign (#) is used with this entry because hyperphosphatasia with mental retardation syndrome-4 (HPMRS4) is caused by homozygous or compound heterozygous mutation in the PGAP3 gene (611801) on chromosome 17q12.Hyperphosphatasia with mental retardation syndrome-4 is an autosomal recessive neurologic disorder characterized by severely delayed psychomotor development, mental retardation, lack of speech acquisition, seizures, and dysmorphic facial features. Laboratory studies show increased serum alkaline phosphatase (summary by Howard et al., 2014).

For a discussion of genetic heterogeneity of HPMRS, see HPMRS1 (239300).

Clinical features

Howard et al. (2014) reported 5 patients from 3 families with HPMRS4. One of the patients had previously been reported by Thompson et al. (2012). All patients had severely delayed psychomotor development since early infancy, with hypotonia and inability to speak or walk independently. Four patients developed seizures between ages 18 months and 12 years; 3 had generalized seizures and 1 had myoclonic seizures. Dysmorphic facial features included hypertelorism, upslanting palpebral fissures, broad nasal bridge, short nose, long philtrum, tented upper lip, full cheeks, and large fleshy earlobes. Three sibs in 1 family had postnatal microcephaly (-2 to -3 SD). Two patients had cleft palate, and brain MRI of 1 patient showed thin corpus callosum and dilated lateral ventricles. Laboratory studies showed increased serum alkaline phosphatase. Brachytelephalangy was not present.

Inheritance

The transmission pattern in the families with HPMRS4 reported by Howard et al. (2014) was consistent with autosomal recessive inheritance.

Molecular genetics

In 5 patients from 3 families with HPMRS4, Howard et al. (2014) identified homozygous or compound heterozygous mutations in the PGAP3 gene (611801.0001-611801.0004). The mutation in the first family was found by exome sequencing. Transfection of wildtype PGAP3 into CHO cells that lack both PGAP3 and PGAP2 (615187) restored the first step in fatty acid remodeling, but the second step remained defective, leading to a reduction in surface level...

Symptoms

INHERITANCE: Autosomal recessive

GROWTH: [Other]; Poor growth (1 patient)

HEAD AND NECK: [Head]; Microcephaly (-2 to -3 SD) (in some patients); [Ears]; Large fleshy earlobes; [Eyes]; Hypertelorism; Upslanting palpebral fissures; [Nose]; Broad nasal bridge; Broad nasal tip; [Mouth]; Tented upper lip; Thin upper lip; Cleft palate (in some patients); Bruxism

MUSCLE, SOFT TISSUE: Hypotonia

NEUROLOGIC: [Central nervous system]; Delayed psychomotor development, severe; Inability to walk; Lack of speech development; Seizures, generalized; Seizures, myoclonic; Involuntary movements

LABORATORY ABNORMALITIES: Increased serum alkaline phosphatase

MISCELLANEOUS: Onset in infancy

MOLECULAR BASIS: Caused by mutation in the post-GPI attachment to proteins 3 gene (PGAP3, 611801.0001)
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Chromosome 10q26 deletion syndrome

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

Cytogenetics

A number sign (#) is used with this entry because it represents a contiguous gene deletion syndrome.Lewandowski et al. (1978) first reported a patient with partial deletion of chromosome 10q. Shapiro et al. (1985) reported 8 unrelated patients with deletions of various segments of chromosome 10q.

Clinical features

Mehta et al. (1987) reported a boy with deletion of chromosome 10q26. He showed developmental delay and moderate mental retardation. Physical characteristics included short stature, microcephaly, dolichocephaly, triangular face, prominent nasal root with beaked nose and flared nostrils, long philtrum, small pointed jaw, and convergent strabismus. He also had fifth finger clinodactyly, limited elbow extension, and undescended testes. All who worked with him noted hyperkinesis and aggressive behavior with limited attention span and diminished need for sleep. He alternated between being provocative or destructive and affectionate.

Tanabe et al. (1999) reported a mal...

Symptoms

INHERITANCE: Autosomal dominant

GROWTH: [Height]; Short stature; [Weight]; Low birth weight; [Other]; Postnatal growth retardation

HEAD AND NECK: [Head]; Microcephaly; Dolichocephaly; Frontal bossing; [Face]; Facial asymmetry; Triangular face; Long philtrum; Micrognathia; [Ears]; Prominent ears; Low-set ears; Rotated ears; Hearing loss, sensorineural (in patients with larger deletions); Structural inner ear abnormalities (in patients with larger deletions); Vestibular anomalies (less common); [Eyes]; Strabismus; Hypertelorism; Downslanting palpebral fissures; Upslanting palpebral fissures; Epicanthal folds; [Nose]; Prominent nose; Broad nasal bridge; Beaked nose; Flared nostrils; [Mouth]; Thin upper lip; [Neck]; Short neck; Webbed neck

CARDIOVASCULAR: [Heart]; Atrial septal defect (less common); [Vascular]; Patent ductus arteriosus (less common)

CHEST: [External features]; Widely spaced nipples

GENITOURINARY: [External genitalia, male]; Micropenis; Hypoplastic scrotum; [Internal genitalia, male]; Cryptorchidism; [Bladder]; Vesicoureteric reflux (less common)

SKELETAL: [Skull]; Craniosynostosis (reported in 1 patient); [Limbs]; Limited elbow extension; [Hands]; Clinodactyly; Syndactyly; [Feet]; Clinodactyly; Syndactyly

SKIN, NAILS, HAIR: [Hair]; Low posterior hairline; [Nails]; Nail hypoplasia

NEUROLOGIC: [Central nervous system]; Hypotonia; Seizures; Developmental delay, variable; Mental retardation; Wide-based gait; Vestibular anomalies (less common); Speech and language delay; Learning difficulties; [Behavioral/psychiatric manifestations]; Aggressive behavior; Hyperactivity; Poor attention span; Affectionate behavior

LABORATORY ABNORMALITIES: Cytogenetic d...
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Goldberg-Shprintzen megacolon syndrome

Retrieved: 27-07-2015
Source: GARD (Original article)
Associated genes: kiaa1279

Goldberg-Shprintzen megacolon syndrome

Goldberg-Shprintzen megacolon syndrome is a very rare genetic condition characterized by Hirschsprung disease, megacolon, small head, widely spaced eyes, cleft palate, short stature, and learning disability. This condition has been described in about 15 individuals to date. Some of the reported cases also had iris coloboma, hypotonia, epilepsy, and ptosis. One of the described patients had sparse scalp hair, a sloping forehead, sparse eyebrows, broad nasal bridge, large ears, pointed chin, ventricular septal defect, hypospadias, syndactyly between the second and third fingers, and clubfeet. This condition appears to be inherited as an autosomal recessive trait and was found to be caused by mutations in the KIAA1279 gene
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Goldberg-Shprintzen megacolon syndrome

Retrieved: 27-07-2015
Source: Orphanet (Original article)
Associated genes: kiaa1279

Goldberg-Shprintzen megacolon syndrome is a multiple malformation syndrome characterized by Hirschprung megacolon with microcephaly, hypertelorism, submucous cleft palate, short stature and learning disability. It has been described in about 10 patients, boys and girls. Some of the reported cases also had iris coloboma, hypotonia, and ptosis. One of the described patients had sparse scalp hair, a sloping forehead, sparse eyebrows, telecanthus, broad nasal bridge, large ears, pointed chin, ventricular septal defect, hypospadias with bifid scrotum, cutaneous syndactyly between the second and third fingers, and rocker bottom feet. The Goldberg-Shprintzen megacolon syndrome appears to be inherited as an autosomal recessive trait and was found to be caused by mutations in KIAA1279 on chromosome 10q21.3-q22.1. Severe constipation and abdominal distention lead to diagnosis of congenital megacolon in the first few days of life. Histological findings from rectal biopsy show aganglionosis of the submucosal plexus and confirm Hirschsprung disease. Colostomy may be performed in an emergency. In some patients, epilepsy appears in the first months. Computerised tomography (CT) and magnetic resonance imaging (MRI) of the brain should be carried out in order to evaluate the consequences of microcephaly and/or to search for causes of epilepsy. They may show polymicrogyria (malformation of the cerebral cortex characterized by an increased number of smaller circonconvolutions or gyri), ventriculomegaly, loss of parenchymal volume (brain atrophy or hypoplasia, especially of the white matter), thin and hypoplastic corpus callosum, and variable disruption of cerebral cortical structure. Genetic counseling should inform parents of an affected child of a recurrence risk of 25% for each subsequent pregnancy. No case of prenatal diagnosis has been reported so far, but after the birth of an index case, the syndrome might be suspected if microcephaly, growth retardation and/or hyperec...
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Goldberg–Shprintzen syndrome

Retrieved: 27-07-2015
Source: WIKIPEDIA (Original article)
Associated genes: kiaa1279
Goldberg–Shprintzen is a condition associated with mutations in KIAA1279 gene. Hirschsprung's disease may be part of the presentation.

Ciliary dyskinesia, primary, 31

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

Clinical features

A number sign (#) is used with this entry because of evidence that primary ciliary dyskinesia-31 (CILD31) is caused by compound heterozygous mutation in the CENPF gene (600236) on chromosome 1q32.

For a phenotypic description and a discussion of genetic heterogeneity of primary ciliary dyskinesia, see CILD1 (244400).Waters et al. (2015) reported a Caucasian family in which 4 fetuses had an embryonic lethal ciliopathy phenotype. The fetuses died in midgestation, and autopsy showed hydrocephalus, cerebellar hypoplasia, agenesis of the corpus callosum, duodenal atresia, gastrointestinal malrotation, and renal hypodysplasia. Abnormal craniofacial features included microcephaly, cleft palate, micrognathia, hypertelorism, low-set ears, prominent nose, broad nasal root, and high nasal bridge.

- Clinical Variability

Waters et al. (2015) reported a patient with microcephaly and mild to moderate learning disabilities who was compound heterozygous for 2 truncating mutations in the CENPF gene (600236.0001 and 600236.0003). Other body systems were unaffected and overall growth was normal.

Inheritance

The transmission pattern in the family with CILD31 reported by Waters et al. (2015) was consistent with autosomal recessive inheritance.

Molecular genetics

In 4 affected fetuses from a nonconsanguineous Caucasian family with CILD31, Waters et al. (2015) identified compound heterozygous mutations in the CENPF gene (600236.0001 and 600236.0002). The mutations were found by whole-exome sequencing. Exome sequencing of the CENPF gene in 1,000 patients with microcephaly further identified 1 patient who was compound heterozygous for 2 truncating mutations (600236.0001 and 600236.0003). Renal epithelial cells from the fetuses from the first family showed that the cilia were shortened compared to controls, consistent with defective ciliogenesis.

Animal model

Waters et al. (2015) found that morpholino knockdown of cenpf in zebrafish embryos resulted in decreased survival and a ciliopathy phenotype, including axis curvature defects, abnormal heart looping, hydrocephalus, and pronephric cysts. Mutant zebrafish also showed left-right patterning defects and shortened Kupffer vesicle cilia compared to controls.

Symptoms

INHERITANCE: Autosomal recessive

HEAD AND NECK: [Head]; Microcephaly; [Face]; Micrognathia; [Ears]; Low-set ears; [Eyes]; Hypertelorism; [Nose]; Broad nasal bridge; High nasal bridge; Short columella; [Mouth]; Cleft palate

ABDOMEN: [Gastrointestinal]; Duodenal atresia

GENITOURINARY: [Kidneys]; Renal hypodysplasia

NEUROLOGIC: [Central nervous system]; Learning disabilities (1 patient); Hydrocephalus; Agenesis of the corpus callosum; Cerebellar hypoplasia

MISCELLANEOUS: Four sibs from 1 family died in utero mid-gestation; One unrelated patient had only mild microcephaly and learning disabilities

MOLECULAR BASIS: Caused by mutation in the centromeric protein F gene (CENPF, 600236.0001)
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Tel Hashomer camptodactyly syndrome

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

Tel Hashomer camptodactyly syndrome is a rare syndrome characterized by camptodactyly, muscle hypoplasia and weakness, skeletal anomalies, facial dysmorphism and abnormal dermatoglyphics. Up to 2005, 20 cases had been reported. Dysmorphic features include facial asymmetry, hypertelorism, broad nasal bridge, long philtrum and a small mouth. Winging scapulae, scoliosis, syndactyly and clinodactyly are commonly observed. The affected patients usually have normal mental development. The molecular basis of the syndrome has not yet been elucidated. Inheritance is probably autosomal recessive. Last update: January 2011
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Chromosome 15q26-qter deletion syndrome

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

Clinical features

A number sign (#) is used with this entry because it represents a contiguous gene deletion syndrome.Drayer et al. (1977) reported 2 sibs with mental retardation and multiple congenital anomalies, including facial dysmorphism, and skeletal abnormalities. Rump et al. (2008) provided a follow-up of the patients reported by Drayer et al. (1977). Both patients were born with microcephaly and showed growth retardation with failure to thrive. The older sister had excessive scalp hair, a broad nasal bridge, epicanthal folds, blepharophimosis, strabismus, low-set dysplastic ears, hyperextensible joints, and perceptive hearing loss. The younger brother had broad nasal bridge, epicanthal folds, blepharophimosis, divergent strabismus, low-set dysplastic ears, bilateral hearing loss, and an atrial septal defect. Both had moderate to severe mental retardation. Both also had brachydactyly characterized by short second and fifth fingers, small thumbs, and talipes equinovarus. Nails were normal. Radiographs showed absence of the middle phalanges of the second and fifth fingers, short middle phalanges of the third and fourth fingers, and short proximal phalanges of the thumbs. The toes also showed absent phalanges. There were no obvious anomalies of the internal organs.

Roback et al. (1991) described a patient with a chromosome 15q26.1-qter deletion and monozygosity for the insulin-like growth factor I receptor gene (IGF1R; 147370). Clinical features included intrauterine growth retardation (IUGR), microcephaly, micrognathia, renal anomalies, lung hypoplasia, and delayed growth and development. The authors reviewed the clinical findings in patients with similar chromosome 15 deletions and speculated that the loss of an IGF1R allele may be related to the severe IUGR and postnatal growth deficiency observed in their patient and other patients with distal 15q deletions.

Tonnies et al. (2001) reported a girl wit...

Symptoms

INHERITANCE: Isolated cases

GROWTH: [Height]; Short stature; [Weight]; Low birth weight; [Other]; Intrauterine growth retardation; Failure to thrive

HEAD AND NECK: [Head]; Microcephaly; [Face]; Micrognathia; Triangular facies; [Ears]; Low-set ears; [Eyes]; Strabismus; Blepharophimosis; [Nose]; Broad nasal bridge

CARDIOVASCULAR: [Heart]; Congenital cardiac anomalies; Septal defects

GENITOURINARY: [External genitalia, male]; Hypospadias; Cryptorchidism; Micropenis

SKELETAL: [Hands]; Brachydactyly; Absence or hypoplastic middle phalanges; [Feet]; Talipes equinovarus; Brachydactyly; Absence or hypoplastic middle phalanges

NEUROLOGIC: [Central nervous system]; Delayed psychomotor development; Mental retardation

MISCELLANEOUS: Onset in utero; Variable phenotype

MOLECULAR BASIS: A contiguous gene deletion syndrome caused by deletion (5.8 Mb) of chromosome 15q26-qter encompassing the IGF1R gene (147370)
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Chromosome xq28 duplication syndrome

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

Clinical features

A number sign (#) is used with this entry because this disorder is caused by copy number increase of a small region on distal chromosome Xq28. One report has identified a 0.3-Mb region of Xq28 (chrX:153.2-153.5 Mb, NCBI36) containing at least 11 genes and including the GDI1 gene (300104), which is mutated in MRX41 (300849). Two additional reports have identified a more distal 0.5-Mb region (chrX:153.7-154.2 Mb (NCBI36/hg19)) containing at least 8 genes and including the RAB39B gene (300774), which is mutated in MRX72 (300271).Vandewalle et al. (2009) reported 4 families with X-linked mental retardation. The first family was of Belgian origin and had 4 affected males in 2 generations. All had normal growth, moderate mental retardation, and variable mild dysmorphic features, including mild 2-3 toe syndactyly, ataxic gait, and strabismus. The second family was of German origin and consisted of 2 affected brothers. The older brother was of average gestational size but was very floppy and was found to have a classic Dandy-Walker malformation, with cerebellar hypoplasia and agenesis of the corpus callosum. He developed seizures at 15 months of age and was microcephalic. Dysmorphic features included large ears, upslanting palpebral fissures, epicanthal folds, and thin lips. His brother also had a Dandy-Walker malformation, with agenesis of the cerebellar vermis and hypoplasia of the corpus callosum. At 19 months he had not developed seizures but had microcephaly. The third family reported by Vandewalle et al. (2009) was of Spanish origin and was reported as case 6 by Madrigal et al. (2007). The index case was born to nonconsanguineous parents at 8 months of pregnancy complicated by an acute pancreatitis. He developed neonatal seizures and cyanotic crises, and was hospitalized for 10 days. Imaging of his brain showed ventricular dilatation and large asymmetric cisterna magna. Gross motor milestones were within normal range. His speech development was delayed. At age 7, he had mild dysmorphic features with microcephaly, a high palate, medial eyebrow flare, and prominent ears. His IQ was 58. Neurologic examination was normal. No clinical details were available for 2 maternal brothers who were institutionalized. The fourth family was a sporadic case born to healthy, unrelated German parents. He had mild global psychomotor delay and did not begin walking until 20 months of age. Mild dysmorphic features were present, including brachycephaly, broad forehead, hypotelorism, and epicanthus inversus, more pronounced at the left side. He had a rather flat midface with flat nasal root and a short philtrum. He had a high palate and a small chin. Head circumference was at the 25th percentile.

In addition to mental retardation and dysmorphic features, Vandewalle et al. (2009) found ventricular aberrations in 2 families. A large fourth ventricle was seen in family 1, and a ventricular dilatation in family 3.

Cytogenetics

El-Hattab et al. (2011) reported 4 boys, ...
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Mental retardation, buenos aires type

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

Clinical features

Among the children of a consanguineous mating, Mutchinick (1972) described 2 with an apparently distinctive syndrome of mental and physical retardation, peculiar facies, and heart and renal malformations. True microcephaly and Seckel dwarfism were suggested but for one or another reason did not satisfy the features of these cases.

Doerfler et al. (1997) examined 2 brothers from the Ruhr area in Germany with a phenotype similar to that described by Mutchinick (1972). A third brother with multiple malformations had died in infancy. On further investigation they found that the 2 sib pairs, that from Argentina and that from Germany, now living some 12,000 km apart, originated from the same geographic region in Poland. The 3 brothers described by Doerfler et al. (1997) came from a nonconsanguineous family and showed microcephaly, mental and physical retardation, speech disorder, facial anomalies, and internal hydrocephalus. The youngest brother died at the age of 5 months. He had situs abdominalis inversus and atrial septal defect, and had been operated on for internal hydrocephalus and atresia of the biliary duct.

Tonoki et al. (1999) described a Japanese girl with Mutchinick syndrome, indicating that it is not restricted to descendants of individuals from East Prussia.

Symptoms

INHERITANCE: Autosomal recessive

GROWTH: [Other]; Failure to thrive

HEAD AND NECK: [Head]; Microcephaly; [Face]; High forehead; Prognathism; [Ears]; Low-set ears; Protruding ears; [Eyes]; Strabismus; Myopia; Hypertelorism; Ptosis; Downslanting palpebral fissure; Long, curly eyelashes; Light blue irides; [Nose]; Prominent nose; Broad nasal bridge; [Mouth]; Large mouth; Thin upper lip; High-arched palate; [Teeth]; Dental malocclusion; Irregular ridges on incisors; Carious teeth

CARDIOVASCULAR: [Heart]; Atrial septal defect

CHEST: [Ribs, sternum, clavicles, and scapulae]; Pectus excavatum; Pectus carinatum

ABDOMEN: Situs abdominalis inversus; [Biliary tract]; Intrahepatic atresia of biliary duct; [Gastrointestinal]; Feeding problems

GENITOURINARY: [External genitalia, male]; Hypospadias; [Kidneys]; Calyceal dilation

SKELETAL: [Spine]; Cuboid-shaped thoracolumbar vertebral bodies; [Hands]; Fifth finger clinodactyly; Hyperconvex thumb nails; [Feet]; Pes planus

SKIN, NAILS, HAIR: [Nails]; Hyperconvex thumb nails; [Hair]; Long, curly eyelashes; Blond hair

NEUROLOGIC: [Central nervous system]; Mental retardation; Hydrocephalus; Partial agenesis of corpus callosum; Spastic gait
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Chromosome 3q29 duplication syndrome

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

Clinical features

A number sign (#) is used with this entry because the phenotype is caused by a microduplication of chromosome 3q29 (chr3: 197.1-198.9 Mb, NCBI35).

See also 609425 for a chromosome 3q29 deletion syndrome.Lisi et al. (2008) reported a 3-generation family in which 5 members had mild to moderate mental retardation and minor dysmorphic features associated with an interstitial microduplication of chromosome 3q29. Clinical features included microcephaly, round face, bulbous nose, short or downslanting palpebral fissures, excessive hand creases, and pes planus.

Cytogenetics

By FISH analysis, array comparative genomic hybridization (CGH), and SNP genotype analysis Lisi et al. (2008) found the microduplication of chromosome 3q29 was between 1.61 and 1.76 Mb in size, with the breakpoints occurring between 2 nearly identical low-copy repeat sequences. The proximal break occurred between SNP dbSNP rs11926771 (base position 197,145,041) and SNP dbSNP rs6797622 (base position 197,223,225), while the distal breakpoint occurred between SNP dbSNP rs11922324 (base position 198,832,486) and SNP dbSNP rs6583248 (base position 198,910,079) (NCBI35).

Symptoms

INHERITANCE: Autosomal dominant

GROWTH: [Weight]; Obesity

HEAD AND NECK: [Head]; Microcephaly; [Face]; Round face; Long face; [Eyes]; Downslanted palpebral fissures; Short palpebral fissures; Large eyes; [Nose]; Bulbous nose; Short nose; Wide nasal bridge; Broad nasal bridge

SKELETAL: [Hands]; Excessive hand creases; [Feet]; Pes planus

SKIN, NAILS, HAIR: [Hair]; Low posterior hairline

NEUROLOGIC: [Central nervous system]; Cognitive delay; Mental retardation, mild to moderate

LABORATORY ABNORMALITIES: 1.61- and 1.76-Mb microduplication of 3q29

MOLECULAR BASIS: Caused by microduplication of 3q29.
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Chromosome 3q29 microduplication syndrome

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

Chromosome 3q29 microduplication syndrome

Chromosome 3q29 microduplication syndrome is a rare chromosome abnormality characterized by having an extra copy of material (duplication) on a specific part of the long arm of chromosome 3. The signs and symptoms vary among affected individuals, but the most common features include mild or moderate intellectual disability and microcephaly. The condition may occur for the first time in the affected individual (de novo) or it can be inherited from a mildly affected or apparently normal parent. Treatment is directed toward the specific signs and symptoms present in each individual
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3q29 microduplication

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

3q29 microduplications are recently described chromosomal abnormalities with unclear clinical significance. They have been reported in fewer than 30 patients. The clinical phenotype is extremely variable and the most consistent features are mild or moderate intellectual deficit and microcephaly. Among duplications, only some appear to be the reciprocal duplication products of 3q29 microdeletion (see this term) and the others flank, span, or partially overlap the common deletion region. These results suggest that other mechanisms in addition to non-allelic homologous recombination (NAHR) mediate rearrangements of 3q29. These microduplications appear de novo or are inherited from mildly affected or completely normal parents. The clinical significance of reciprocal 3q29 microduplication is still unclear. Expert reviewer(s) Dr Nicole MORICHON-DELVALLEZ Last update: March 2011
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Hyperphosphatasia with mental retardation syndrome 2

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

Description

A number sign (#) is used with this entry because hyperphosphatasia with mental retardation syndrome-2 (HPRMS2) can be caused by compound heterozygous mutation in the PIGO gene (614730) on chromosome 9p13.Hyperphosphatasia with mental retardation syndrome-2 is an autosomal recessive disorder characterized by moderately to severely delayed psychomotor development, facial dysmorphism, brachytelephalangy, and increased serum alkaline phosphatase (hyperphosphatasia). Some patients may have additional features, such as cardiac septal defects or seizures (summary by Krawitz et al., 2012).

Clinical features

Krawitz et al. (2012) reported 2 sisters, born of unrelated British parents, and an unrelated girl with hyperphosphatasia with mental retardation. All 3 patients had normal birth parameters, but were born with anal stenosis or anal atresia with perineal fistula. One of the sisters had vesicoureteral reflux. The unrelated girl also had atrial septal defect, peripheral pulmonary stenosis, left coronal synostosis causing plagiocephaly, enlarged ventricles, and microcephaly (-5 SD). Two of the patients showed poor growth. Psychomotor development was moderately to severely retarded and all showed hypotonia. The unrelated girl died at age 22 months of severe generalized seizures. Common facial features in these patients included wide-set eyes with long palpebral fissures, short nose with broad nasal bridge and tip, and a tented mouth. Fingers showed nail hypoplasia, especially of the second, fourth, and fifth digits, and absent nails of the fifth digits. The halluces were broad, but the toes showed small nails or aplasia of nails, especially of the fourth and fifths digits, all findings consistent with b...

Symptoms

INHERITANCE: Autosomal recessive

GROWTH: [Other]; Poor growth

HEAD AND NECK: [Head]; Microcephaly (1 patient); [Eyes]; Hypertelorism; Long palpebral fissures; [Nose]; Short nose; Broad nasal bridge; Broad nasal tip; [Mouth]; Tented mouth

CARDIOVASCULAR: [Heart]; Atrial septal defect (1 patient)

ABDOMEN: [Gastrointestinal]; Anal stenosis; Anal atresia

GENITOURINARY: [Bladder]; Vesicoureteral reflux (1 patient)

SKELETAL: [Skull]; Plagiocephaly (1 patient); Coronal synostosis (1 patient); [Hands]; Brachytelephalangy; [Feet]; Brachytelephalangy; Broad halluces

SKIN, NAILS, HAIR: [Nails]; Hypoplastic or absent nails

NEUROLOGIC: [Central nervous system]; Delayed psychomotor development, moderate to severe; Delayed speech and language development; Hypotonia; Seizures (1 patient); Enlarged ventricles (1 patient)

LABORATORY ABNORMALITIES: Increased serum alkaline phosphatase; Hyperphosphatasia

MISCELLANEOUS: Onset at birth; Three patients (2 sisters and 1 unrelated female) have been reported (last curated July 2012)

MOLECULAR BASIS: Caused by mutation in the phosphatidylinositol glycan, class O gene (PIGO, 614730.0001)
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Chromosome 14q11-q22 deletion syndrome

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

Clinical features

A number sign (#) is used with this entry because it represents a contiguous gene deletion syndrome.Grammatico et al. (1994) reported a boy with severe psychomotor retardation and dysmorphic features associated with a small de novo interstitial deletion of chromosome 14q11.2-q13 identified by karyotype analysis. In the first months of life, he was noted to have microcephaly with plagiocephaly, spastic tetraparesis, left hip subluxation, and poor growth. Dysmorphic features included upslanting palpebral fissures, flat nasal bridge with enlarged nares, and poorly folded auricular lobes. He also had cryptorchidism and low implanted thumbs. Neurologic examination at age 3 years showed autistic-like behavior, inability to follow with the eyes, vertical nystagmus, and inability to sit or walk unsupported.

Shapira et al. (1994) reported 2 unrelated girls, of Hispanic and Vietnamese descent, respectively, with psychomotor delay and failure to thrive associated with de novo deletions of proximal 14q. Common features included microcephaly, poor growth, and hypoplasia of the corpus callosum. Both had dysmorphic features, which varied somewhat. The first girl had triangular face, high-arched palate, and prominent chin. Other features included generalized hypertonia, brisk tendon reflexes, poor head control, and inability to fix and follow visually. The second girl had plagiocephaly, open anterior fontanel, prominent forehead, asymmetric low-set, posteriorly-rotated ears, epicanthal folds, flat nasal bridge, small mouth, and micrognathia. She also had a patent foramen ovale, patent ductus arteriosus, and severe hypotoni...

Symptoms

INHERITANCE: Isolated cases

GROWTH: [Other]; Failure to thrive; Poor growth

HEAD AND NECK: [Head]; Microcephaly; Plagiocephaly; Poor head control; [Face]; Triangular face; Micrognathia; Long philtrum; [Ears]; Low-set ears; Malformed auricles; [Eyes]; Poor eye contact; Lack of fixation; Triangular medial eyebrows with distal tapering; Epicanthal folds; Deep-set eyes; Short palpebral fissures; Widely-spaced eyes; Optic atrophy; Cortical blindness; [Nose]; Short nose; Flat nasal bridge; Broad nose; [Mouth]; Cupid's bow; Small mouth; High-arched palate

CARDIOVASCULAR: [Heart]; Ventricular septal defect (1 patient); Patent foramen ovale (1 patient); [Vascular]; Patent ductus arteriosus (2 patients)

GENITOURINARY: [Internal genitalia, male]; Cryptorchidism

NEUROLOGIC: [Central nervous system]; Hypotonia, neonatal; Delayed psychomotor development; Mental retardation, severe; Inability to walk; Minimal or lack of speech; Hypertonia; Seizures; Spasticity; Hyperreflexia; Hypoplasia of the corpus callosum; Abnormal myelination

MISCELLANEOUS: Variable features; Contiguous gene deletion syndrome

MOLECULAR BASIS: Caused by deletion of 3.0-30.0Mb on 14q11-q22
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Hyperphosphatasia with mental retardation syndrome 1

Retrieved: 27-07-2015
Source: OMIM (Original article)
Associated genes: pgap3, pigv, pigo, pgap2

Description

A number sign (#) is used with this entry because hyperphosphatasia with mental retardation syndrome-1 (HPMRS1) is caused by homozygous or compound heterozygous mutation in the PIGV gene (610274) on chromosome 1p36.Hyperphosphatasia with mental retardation syndrome-1 is an autosomal recessive disorder characterized by mental retardation, various neurologic abnormalities such as seizures and hypotonia, and hyperphosphatasia. Other features include facial dysmorphism and variable degrees of brachytelephalangy (summary by Krawitz et al., 2010).

- Genetic Heterogeneity of Hyperphosphatasia with Mental Retardation Syndrome

See also HPMRS2 (614749), caused by mutation in the PIGO gene (614730) on chromosome 9p13; HPMRS3 (614207), caused by mutation in the PGAP2 gene (615187) on chromosome 11p15; HPMRS4 (615716), caused by mutation in the PGAP3 gene (611801) on chromosome 17q12; and HPMRS5 (616025), caused by mutation in the PIGW gene (610275) on chromosome 17q12.

Clinical features

Mabry et al. (1970) reported 3 sibs and a first cousin with severe mental retardation, seizures, various neurologic abnormalities, and greatly elevated alkaline phosphatase. Both pairs of parents were consanguineous. The alkaline phosphatase present in excess seemed to be of hepatic origin.

Kruse et al. (1988) reported that over a 10-year period they had observed 9 children (6 females) from 6 families who had unexplained persistent hype...

Symptoms

INHERITANCE: Autosomal recessive

HEAD AND NECK: [Face]; Midface hypoplasia; Prognathism; [Eyes]; Hypertelorism; Long palpebral fissures; Arched eyebrows; [Nose]; Broad nasal bridge; Broad nasal tip; [Mouth]; Cleft palate (rare); Short philtrum; Downturned corners of the mouth; Tented mouth

CARDIOVASCULAR: [Heart]; Ventral septal defect (rare)

ABDOMEN: [Gastrointestinal]; Feeding problems necessitating tube feeding (in some patients); Anteriorly displaced anus (in some patients); Anovestibular fistula (in some patients); Anorectal anomalies (in some patients)

SKELETAL: [Skull]; Plagiocephaly; [Hands]; Hypoplastic terminal phalanges (brachytelephalangy); Tapered fingers; [Feet]; Hypoplastic toes (in some patients); Bilateral adducted forefoot (rare)

SKIN, NAILS, HAIR: [Nails]; Hypoplastic nails (in some patients); Curved nails (in some patients)

NEUROLOGIC: [Central nervous system]; Hypotonia; Seizures; Mental retardation, severe; Athetoid and dystonic hand movements (in some patients); Moderate cortical atrophy (in some patients); Delayed myelinization (in some patients); Speech delay (in some patients); No speech development (in most patients)

LABORATORY ABNORMALITIES: Elevated alkaline phosphatase (varies from 1.3-20 times age-adjusted upper limit of normal); Hyperphosphatasia

MOLECULAR BASIS: Caused by mutation in the phosphatidylinositol glycan, class V gene (PIGV, 610274.0001)
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Growth delay due to insulin-like growth factor I resistance

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

Growth delay due to IGF-I resistance is characterised by variable intrauterine and postnatal growth retardation and elevated serum IGF-I levels. Addition features include variable degrees of intellectual deficit, microcephaly and dysmorphism (broad nasal bridge and tip, smooth philtrum, thin upper and everted lower lips, short fingers, clinodactyly, wide-set nipples and pectus excavatum). Prevalence is unknown. IGF-I resistance may be caused by a variety of genetic defects: ring chromosome 15, distal heterozygous 15q deletions encompassing the IGF1R gene (15q26.3), or IGF1R gene mutations. Intellectual deficit is pronounced in patients with ring chromosome 15 but varies depending on the size of the deletion and on the functions of other deleted genes in patients with 15q deletions. Partial IGF-I insensitivity due to IGF1R haploinsufficiency has been reported in one patient with a small deletion encompassing one allele of the IGF1R gene and was characterised by small size for gestational age, persistent growth failure that improved considerably with GH therapy, and the absence of intellectual deficit. IGF1R mutations have been described in six patients so far and were associated with variable growth delay and degrees of intellectual deficit. In all but one of these patients, the mutations were heterozygous and transmitted as an autosomal dominant trait. Diagnosis relies on karyotyping for detection of ring chromosome 15, detection of small deletions encompassing IGF1R and detection of IGF1R mutations by sequence variation screening methods or by direct sequencing of the 21 IGF1R exons and their intron-exon junctions. The differential diagnosis should include bio-inactive IGF-I resulting in IGF-I deficiency (see this term). Measurement of IGF-I levels can be used for diagnosis but circulating levels of IGF-I may vary over time for the same patient and may not be elevated in case of poor nutritional status. Affected families should be offered genetic counselli...
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Juberg-Marsidi syndrome

Retrieved: 27-07-2015
Source: Orphanet (Original article)
Associated genes: atrx, serpina2, mmab, antxr1

Juberg-Marsidi syndrome is an X-linked mental retardation (XLMR) syndrome belonging to the group of conditions characterised by the association of intellectual deficit with hypotonic facies (Mental retardation, X-linked-hypotonic facies; see this term). Prevalence is unknown but since its initial description in 1980 several unrelated families with affected males have been reported. The syndrome is characterised by facial dysmorphism (a flat and broad nasal bridge, prominent forehead, upslanting palpebral fissures, hypertelorism and various ear anomalies), growth failure, sensorineural deafness, microgenitalism and severe intellectual deficit. Inheritance is X-linked recessive and the syndrome is caused by mutations in the ATRX gene (Xq13.3). Last update: May 2008
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Trichorhinophalangeal syndrome type 2

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

Trichorhinophalangeal syndrome type 2

Trichorhinophalangeal syndrome type 2 (TRPS2), also known as Langer-Giedion syndrome, is an extremely rare inherited multisystem disorder. The condition is characterized by intellectual deficit and numerous other abnormalities including excess folds of skin, multiple bony growths (exostoses), characteristic facial features, and cone-shaped phalangeal epiphyses (the growing ends of the bones in the fingers). The range and severity of symptoms varies greatly from person to person. TRPS2 is transmitted in an autosomal dominant manner, but many sporadic cases have been reported. TRPS2 is due to the absence of genetic material (chromosomal deletions) on chromosome 8, which often includes the TRPS1 gene and EXT1 gene. The size of the deletion varies from person to person
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Hamel cerebro-palato-cardiac syndrome

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

Hamel cerebro-palato-cardiac syndrome is an X-linked intellectual disability syndrome (XLMR; see this term) characterized by intellectual deficiency, microcephaly and short stature. It belongs to the group of disorders collectively referred to as Renpenning syndrome (see this term). The prevalence is unknown. It has been reported in a family with 2 brothers and their 2 maternal uncles who presented with severe intellectual deficiency. Marked facial characteristics (abnormal ears, bulbous nose, broad nasal bridge, malar hypoplasia, small mouth, and micrognathia), cleft or highly arched palate, and atrial septal defects were observed. Three out of four patients died in infancy or early childhood. Hamel cerebro-palato-cardiac syndrome represents the more severe phenotypic variant. The syndrome is caused by mutations in the PQBP1 gene. Expansions or reductions in the DR/ER repeat in the polar-amino-acid-rich domain (PRD) are responsible for a truncated protein that is thought to disrupt polyglutamine binding. Hamel cerebro-palato-cardiac syndrome follows an X-linked recessive pattern of inheritance. Genetic testing is possible to identify carrier females and to inform them of the risk of passing on the gene to their offspring. Expert reviewer(s) Pr Vincent DES PORTES Last update: June 2012

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

Filippi syndrome

Filippi syndrome is an extremely rare genetic condition characterized by a small head (microcephaly), webbing of the fingers and toes (syndactyly), intellectual disability, growth delay, and distinctive facial features (high and broad nasal bridge, thin nostrils, small chin or micrognathia, and a high frontal hairline). Other features can include undescended testicles in males, extra fingers (polydactyly), as well as teeth and hair abnormalities. So far, less than 25 cases have been reported in the medical literature. This condition is inherited in an autosomal recessive fashion. The exact underlying genetic cause is not known


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

This syndrome is characterised by microcephaly, severe intellectual deficit, phalangeal anomalies (cutaneous syndactyly of the fingers, toe brachyclinodactyly and nail hypoplasia) and neurological manifestations (epilepsy, spastic/dystonic paraplegia and brisk reflexes). So far, it has been described in three children born to a consanguineous couple of Pakistani origin. Hypotonia, pre- and postnatal growth retardation, a characteristic face (broad forehead with a low frontal hair line, a broad nasal bridge and prominent columella, hypoplastic alae nasi, short philtrum, and a straight mouth with thin lips and downward slanting palpebral fissures) and optic atrophy were also reported. Autosomal recessive inheritance is likely. Last update: April 2008


Retrieved: 27-07-2015
Source: WIKIPEDIA (original)
Associated genes: cask
Mental retardation and microcephaly with pontine and cerebellar hypoplasia (MICPCH), also known as Mental retardation, X-linked, syndromic, Najm type (MRXSNA), is a rare genetic disorder of infants characterised by intellectual disability and pontocerebellar hypoplasia. The disorder is associated with a mutation in the CASK gene which is transmitted in an X-linked manner. As with the vast majority of genetic disorders, there is no known cure to MICPCH.

See also

Pontocerebellar hypoplasia X-linked mental retardation


Retrieved: 27-07-2015
Source: Orphanet (original)
Associated genes: colec11, masp1

This disease has been moved to Craniofacial-ulnar-renal syndrome


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

Clinical features

Simosa et al. (1989) described the cases of a mother and son with high forehead, elongated and flattened face, arched and sparse eyebrows, short palpebral fissures, telecanthus, long nose and hypoplastic nostrils, long philtrum, microstomia, high and narrow palate, nasal speech, chin dimples, and a highly unusual bilateral auricular malformation. Intelligence and hearing were normal. Although to some extent the facies suggested the 'whistling face' syndrome (193700), it appeared to be a distinct entity.

Symptoms

INHERITANCE: Autosomal dominant

HEAD AND NECK: [Face]; Flat facies; Long face; Long philtrum; Chin dimples; Broad forehead; [Ears]; Normal hearing; Low-set ears; Posteriorly rotated ears; Auricular malformation; [Eyes]; Arched, sparse eyebrows; Telecanthus; Blepharophimosis; [Nose]; Long nose; Hypoplastic nostrils; Broad nasal bridge; Flattened nasal tip; [Mouth]; Microstomia; High, narrow palate

GENITOURINARY: [External genitalia, male]; Inguinal hernia

SKIN, NAILS, HAIR: [Skin]; Chin dimples; [Hair]; Arched, sparse eyebrows

VOICE: Nasal speech


Retrieved: 27-07-2015
Source: GARD (original)
Associated genes: cd6, kit, myh11, flt3

Trisomy 22

Trisomy 22 is a chromosome disorder in which an extra (third) copy of chromosome 22 is present in every cell of the body where there should normally only be two copies. This condition is commonly found in miscarriages, but only rarely in liveborn infants. Most affected individuals die shortly before or shortly after birth due to severe complications. Common features include an underdeveloped midface (midface hypoplasia) with flat/broad nasal bridge, malformed ears with pits or tags, cleft palate, hypertelorism (wide-spaced eyes), microcephaly and other cranial abnormalities, congenital heart disease, genital abnormalities, and intrauterine growth restriction (IUGR)


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

This syndrome is characterized by nasopalpebral lipomas, bilateral lid coloboma, and telecanthus. It has been described in less than 30 patients. Other manifestations may include maxillary hypoplasia, hypertelorism, and dysmorphic features. It is transmitted as an autosomal dominant trait with complete penetrance. Surgery can be performed to repair the eyelid coloboma and remove the bilateral nasopalpebral lipomas. Last update: December 2006


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

This disease has been moved to Microcephalic osteodysplastic primordial dwarfism type II


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

Clinical features

A number sign (#) is used with this entry because of evidence that Helsmoortel-Van der Aa syndrome (HVDAS) is caused by heterozygous mutation in the ADNP gene (611386) on chromosome 20q13.Helsmoortel et al. (2014) reported 10 unrelated children with intellectual disability, autism spectrum disorder, and dysmorphic facial features. The patients were ascertained from several large cohorts of individuals with similar features. Nine of the 10 patients had developmental delay apparent in infancy, and 5 of the patients had severe intellectual disability in childhood, with some being nonverbal. Neuropsychiatric features were relatively common, including attention deficit/hyperactivity disorder, anxiety disorder, obsessive compulsive behavior, and stereotypic behaviors. Other frequent findings included hypotonia, feeding problems in infancy, recurrent infections, short stature, joint laxity, and hand abnormalities. Two patients had seizures and 3 had a congenital heart defect. Dysmorphic features varied, but included prominent forehead, high hairline, downslanting palpebral fissures, notched eyelids, broad nasal bridge, thin upper lip, and smooth philtrum.

Pescosolido et al. (2014) reported a 6-year-old girl with HVDAS who presented in infancy with hypotonia, multiple cyanotic episodes thought to be due to breath holding, and feeding difficulties. She showed global developmental delay with delayed language, attention deficit-hyperactivity disorder, a nonspecific mood disorder, and autistic features. Dysmorphic features included broad forehead and slightly tented lips. She also had visual problems, including hypermetropia, cortical visual impairment, exotropia, mild amblyopia, and astigmatism. Treatment resulted in significant improvement in her...

Symptoms

INHERITANCE: Autosomal dominant

GROWTH: [Height]; Short stature; [Weight]; Obesity

HEAD AND NECK: [Head]; Prominent forehead; [Face]; Smooth philtrum; [Eyes]; Downslanting palpebral fissures; Notched eyelid; Ptosis; Strabismus; Hypermetropia; Visual impairment; [Nose]; Broad nasal bridge; Short nose; [Mouth]; Thin upper lip

CARDIOVASCULAR: [Heart]; Congenital heart defect (less common)

ABDOMEN: [Gastrointestinal]; Feeding difficulties

SKELETAL: Joint laxity; [Hands]; Small hands

MUSCLE, SOFT TISSUE: Hypotonia

NEUROLOGIC: [Central nervous system]; Delayed psychomotor development; Developmental delay apparent in infancy; Intellectual disability, mild to severe; Language impairment; Seizures (less common); [Behavioral/psychiatric manifestations]; Autism spectrum disorder; Obsessive-compulsive behavior; Stereotypic behavior; Hyperactivity

IMMUNOLOGY: Recurrent infections

MISCELLANEOUS: Onset in infancy; Variable extraneurologic features

MOLECULAR BASIS: Caused by mutation in the activity-dependent neuroprotector homeobox gene (ADNP, 611386.0001)


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

This disease is described under Rhizomelic chondrodysplasia punctata


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

Clinical features

Tutuncuoglu et al. (1996) described a 46,XY Turkish male infant with microcephaly, severe hypoplasia of the corpus callosum, exophthalmos, cleft lip and palate, seizures, and psychomotor retardation. His parents were first cousins. A similar case was reported by Howard and Young (1988), but their patient also had preaxial polydactyly. Marles and Chudley (1990) described similar findings in a 9-month-old boy: failure to thrive, developmental delay, bilateral cleft lip and palate, and left preaxial polydactyly. The boy had a broad nasal bridge and bilateral epicanthic folds. A right inguinal hernia was repaired surgically. The parents were not related.

Inheritance

Tutuncuoglu et al. (1996) suggested that this condition may be an autosomal recessive disorder.

Symptoms

Head: Microcephaly

Neuro: Hypoplasia of corpus callosum; Seizures; Psychomotor retardation

Eyes: Exophthalmos

Mouth: Cleft lip/palate

Limbs: Preaxial polydactyly

Inheritance: Autosomal recessive


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

Description

Pallister et al. (1974) described 2 brothers with a mental retardation syndrome characterized by an unusual physiognomy (frontal prominence), anterior cowlick, hypertelorism, antimongoloid orbital slant, and broad, flat nasal bridge like that of the OPD syndrome (311300), midline notch of upper lip and submucous cleft of the hard palate, absent upper central incisors, limited motion at the elbow due to subluxation, camptodactyly, and pes cavus. In addition to the mental retardation, the patients had grand mal seizures. The mother and a sister were considered mildly affected, consistent with heterozygous manifestation of an X-linked trait. Bottani and Schinzel (1993) described a patient thought to have this disorder. Severe mental retardation with seizures was associated with a pattern of facial dysmorphism, including high broad forehead, downslanting palpebral fissures, hypertelorism, peculiar nose, and peculiar upper lip with a median notch (incomplete midline oral cleft). The face was compared to that of a boxer, i.e., pugilistic face.

Goizet et al. (1999) reported 3 patients with the Pallister W syndrome and reviewed the 4 patients in 2 separate families that had previously been described. Constant features seemed to be characteristic facies with prominent mandible and pugilistic appearance, and central nervous system involvement with strabismus, spasticity, and moderate to severe mental retardation.

Symptoms

Neuro: Mental retardation; Seizures; Mild spasticity

Facies: Frontal prominence

Eyes: Hypertelorism; Telecanthus; Down-slanting palpebral fissures; Alternating esotropia

Nose: Broad nasal bridge; Flat nasal bridge Broad nasal tip

Mouth: Midline notch of upper lip; Submucous cleft hard palate; Broad uvula

Teeth: Absent upper central incisors

Hair: Anterior cowlick

Joints: Limited elbow motion due to subluxation

Limbs: Cubitus valgus; Short ulna; Bowed radius; Camptodactyly; Clinodactyly; Pes cavus; Metatarsus varus; Pes planus

Inheritance: X-linked

Smith-Magenis syndrome

El síndrome de Smith-Magenis es un trastorno genético que afecta muchos órganos y sistemas del cuerpo y que se debe a una delección (pérdida) de material genético en una región especifica del cromosoma 17.Aunque esta región contiene varios genes, los investigadores creen que esta asociada con la pérdida de un gen particular, RAI1. La mayoría de los casos no se heredan. Se caracteriza por un atraso intelectual moderado, atraso en el lenguaje y algunas características del rostro que son distintivas. El tratamiento es de apoyo


Retrieved: 27-07-2015
Source: OMIM (original)
Associated genes: cyp11b2, hbhr, hba2, hba1

Clinical features

A number sign (#) is used with this entry because of evidence that the disorder represents a contiguous gene syndrome due to a deletion in chromosome 16p that involves the alpha-1 (HBA1; 141800) and alpha-2 (HBA2; 141850) genes, among others.

X-linked alpha-thalassemia/mental retardation syndrome (ATR-X; 301040) is a similar phenotypic disorder caused by mutation in the ATRX gene (300032).Weatherall et al. (1981) reported the association of hemoglobin H disease (Hb H; see alpha-thalassemias, 141800) and mental retardation in 3 unrelated patients of northern European descent.

Hjelle et al. (1982) described a somewhat similar case in a male of northern European extraction. Hb H was associated with multiple congenital anomalies: spina bifida from T6 to the sacrum with a T10-L4 myelomeningocele, congenital cataracts, bilateral inguinal hernias, bilateral deformities of the femoral necks, and subluxation of the left hip. One of his 2 sibs also had congenital cataracts, but there was no family history of other congenital anomalies or of fetal wastage. According to restriction enzyme analyses, the father had 2 alpha-globin genes on one chromosome and only 1 gene on the homolog (i.e., was a silent alpha-thalassemia carrier), whereas the mother had cis alpha-thalassemia trait (i.e., 2 alpha genes on 1 chromosome and none on the homolog). T...

Symptoms

INHERITANCE: Autosomal dominant

GROWTH: [Height]; Short stature; [Weight]; Obesity, mild (less common)

HEAD AND NECK: [Head]; Microcephaly; [Face]; Wide, flat, broad forehead; Long philtrum; Retrognathia, mild; [Ears]; Small ears; [Eyes]; Epicanthal folds; Hypertelorism; Downslanting palpebral fissures; Ptosis; [Nose]; Flat, broad nasal bridge; Triangular nasal tip; Anteverted nostrils; [Mouth]; High-arched palate; Protruding tongue; [Teeth]; Crowded teeth; [Neck]; Short neck; Webbed neck

CARDIOVASCULAR: [Vascular]; Patent ductus arteriosus (in 1 reported case)

CHEST: [External features]; Asymmetric chest; [Breasts]; Abnormally placed nipples; Accessory nipple

GENITOURINARY: [External genitalia, male]; Micropenis; Hypospadias; [Internal genitalia, male]; Cryptorchidism

SKELETAL: [Hands]; Clinodactyly of isolated digits; [Feet]; Talipes equinovarus

NEUROLOGIC: [Central nervous system]; Mental retardation, mild to moderate; Seizures (less common)

HEMATOLOGY: Alpha-thalassemia; Microcytic, hypochromic anemia; Hb H inclusions in red blood cells

LABORATORY ABNORMALITIES: Subtelomeric deletion of chromosome 16p; Normal serum ferritin

MISCELLANEOUS: Highly variable phenotype; See also X-linked alpha-thalassemia/mental retardation syndrome (301040); Contiguous gene syndrome

MOLECULAR BASIS: A contiguous gene syndrome caused by deletion of the alpha-1 hemoglobin (141800) and alpha-2 hemoglobin (141850) genes


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

Hypertelorism-hypospadias-polysyndactyly syndrome is a very rare syndrome associating an acro-fronto-facio-nasal dysostosis with genitourinary anomalies. It has been described in three families. Craniofacial manifestations include wide anterior fontanel, flat occiput, hypertelorism, ptosis, proptosis, broad nasal bridge and nasal tip, long philtrum and posteriorly rotated or low set ears. Hypospadias and shawl scrotum are present in all males. Acral manifestations include syndactyly of fingers, broad thumbs or halluces or preaxial polydactyly. The affected patients have no intellectual deficit. The condition seems to be hereditary, and transmitted as an autosomal recessive trait. Last update: October 2010


Retrieved: 27-07-2015
Source: Orphanet (original)
Associated genes: tbc1d24



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

This disease is described under Neuronal ceroid lipofuscinosis


Retrieved: 27-07-2015
Source: OMIM (original)
Associated genes: gatad2b

Clinical features

A number sign (#) is used with this entry because this form of mental retardation (MRD18) is caused by heterozygous mutation in the GATAD2B gene (614998) on chromosome 1q23.De Ligt et al. (2012) reported a girl (patient 69) with global developmental delay who learned to walk at 3 years and had a few single words at age 8. She had tics, high pain threshold, and hypoplasia of the optic nerve. At 34 years of age, she had severe intellectual disability and strabismus and made grimaces. Height and head circumference were normal. Facial characteristics included thin blonde hair, deeply set eyes, tubular nose with a broad nasal tip, and a large mouth with a thin upper lip. The woman was found to have a mutation in the GATAD2B gene. De Ligt et al. (2012) screened a second cohort of 765 individuals with intellectual disability and identified a second mutation in GATAD2B in a patient with severe developmental delay with delayed motor milestones, limited speech, and overlapping facial features.

Willemsen et al. (2013) reported a girl with developmental delay and similar dysmorphic features as the patients reported by de Ligt et al. (2012). The patient was hypotonic in the neonatal period and thereafter showed delayed psychomotor development. She learned to walk at age 2 years and started to speak during the third year, but only spoke 6 words at age 12 years. Her behavior was characterized by hyperactivity, inappropriate laughter, obsession for shiny objects, and mild self-mutilation. She also had strabismus and hypermetropic astigmatism. Facial dysmorphism included a broad forehead, a broad nasal bridge with full nose tip, a broad mouth with wide-spaced central incisors, short philtrum, and long palpebral fissures. She had thin, blond hair. Her fingers were long and she had fleshy hands.

Cytogenetics

Willemsen et al. (2013) reported a girl with intellectual disability associated with a de novo heterozygous 249-kb deletion of chromosome 1q21.3 encompassing 10 genes and disrupting GATAD2B. No other known disease-related genes were in the deleted region. The girl had hypotonia and feeding difficulties in the neonatal period, followed by delayed psychomotor development and poor speech. Medical problems included hypermetropia and strabismus, and she had 1 episode of absence epilepsy. Facial dysmorphism included hypertelorism, a broad forehead, a broad and flat nasal bridge, and a full square tip of the nose. She had thin, blond hair.

Molecular genetics

In 2 patients with severe intellectual disability and similar dysmorphic features, de Ligt et al. (2012) identified heterozygous de novo mutations in the GATAD2B gene: a nonsense mutation (Q470X; 614998.0001) and a frameshift mutation (614998.0002).

In a patient with intellectual disability and dysmorphic features, Willemsen et al. (2013) identified a heterozygous truncating mutation in the GATAD2B gene (614998.0003). Her unaffected mother carried the mutation in mosaic state (10% in peripheral blood leukocytes). ...


Retrieved: 27-07-2015
Source: OMIM (original)
Associated genes: pgap3

Description

A number sign (#) is used with this entry because hyperphosphatasia with mental retardation syndrome-4 (HPMRS4) is caused by homozygous or compound heterozygous mutation in the PGAP3 gene (611801) on chromosome 17q12.Hyperphosphatasia with mental retardation syndrome-4 is an autosomal recessive neurologic disorder characterized by severely delayed psychomotor development, mental retardation, lack of speech acquisition, seizures, and dysmorphic facial features. Laboratory studies show increased serum alkaline phosphatase (summary by Howard et al., 2014).

For a discussion of genetic heterogeneity of HPMRS, see HPMRS1 (239300).

Clinical features

Howard et al. (2014) reported 5 patients from 3 families with HPMRS4. One of the patients had previously been reported by Thompson et al. (2012). All patients had severely delayed psychomotor development since early infancy, with hypotonia and inability to speak or walk independently. Four patients developed seizures between ages 18 months and 12 years; 3 had generalized seizures and 1 had myoclonic seizures. Dysmorphic facial features included hypertelorism, upslanting palpebral fissures, broad nasal bridge, short nose, long philtrum, tented upper lip, full cheeks, and large fleshy earlobes. Three sibs in 1 family had postnatal microcephaly (-2 to -3 SD). Two patients had cleft palate, and brain MRI of 1 patient showed thin corpus callosum and dilated lateral ventricles. Laboratory studies showed increased serum alkaline phosphatase. Brachytelephalangy was not present.

Inheritance

The transmission pattern in the families with HPMRS4 reported by Howard et al. (2014) was consistent with autosomal recessive inheritance.

Molecular genetics

In 5 patients from 3 families with HPMRS4, Howard et al. (2014) identified homozygous or compound heterozygous mutations in the PGAP3 gene (611801.0001-611801.0004). The mutation in the first family was found by exome sequencing. Transfection of wildtype PGAP3 into CHO cells that lack both PGAP3 and PGAP2 (615187) restored the first step in fatty acid remodeling, but the second step remained defective, leading to a reduction in surface level...

Symptoms

INHERITANCE: Autosomal recessive

GROWTH: [Other]; Poor growth (1 patient)

HEAD AND NECK: [Head]; Microcephaly (-2 to -3 SD) (in some patients); [Ears]; Large fleshy earlobes; [Eyes]; Hypertelorism; Upslanting palpebral fissures; [Nose]; Broad nasal bridge; Broad nasal tip; [Mouth]; Tented upper lip; Thin upper lip; Cleft palate (in some patients); Bruxism

MUSCLE, SOFT TISSUE: Hypotonia

NEUROLOGIC: [Central nervous system]; Delayed psychomotor development, severe; Inability to walk; Lack of speech development; Seizures, generalized; Seizures, myoclonic; Involuntary movements

LABORATORY ABNORMALITIES: Increased serum alkaline phosphatase

MISCELLANEOUS: Onset in infancy

MOLECULAR BASIS: Caused by mutation in the post-GPI attachment to proteins 3 gene (PGAP3, 611801.0001)


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

Cytogenetics

A number sign (#) is used with this entry because it represents a contiguous gene deletion syndrome.Lewandowski et al. (1978) first reported a patient with partial deletion of chromosome 10q. Shapiro et al. (1985) reported 8 unrelated patients with deletions of various segments of chromosome 10q.

Clinical features

Mehta et al. (1987) reported a boy with deletion of chromosome 10q26. He showed developmental delay and moderate mental retardation. Physical characteristics included short stature, microcephaly, dolichocephaly, triangular face, prominent nasal root with beaked nose and flared nostrils, long philtrum, small pointed jaw, and convergent strabismus. He also had fifth finger clinodactyly, limited elbow extension, and undescended testes. All who worked with him noted hyperkinesis and aggressive behavior with limited attention span and diminished need for sleep. He alternated between being provocative or destructive and affectionate.

Tanabe et al. (1999) reported a mal...

Symptoms

INHERITANCE: Autosomal dominant

GROWTH: [Height]; Short stature; [Weight]; Low birth weight; [Other]; Postnatal growth retardation

HEAD AND NECK: [Head]; Microcephaly; Dolichocephaly; Frontal bossing; [Face]; Facial asymmetry; Triangular face; Long philtrum; Micrognathia; [Ears]; Prominent ears; Low-set ears; Rotated ears; Hearing loss, sensorineural (in patients with larger deletions); Structural inner ear abnormalities (in patients with larger deletions); Vestibular anomalies (less common); [Eyes]; Strabismus; Hypertelorism; Downslanting palpebral fissures; Upslanting palpebral fissures; Epicanthal folds; [Nose]; Prominent nose; Broad nasal bridge; Beaked nose; Flared nostrils; [Mouth]; Thin upper lip; [Neck]; Short neck; Webbed neck

CARDIOVASCULAR: [Heart]; Atrial septal defect (less common); [Vascular]; Patent ductus arteriosus (less common)

CHEST: [External features]; Widely spaced nipples

GENITOURINARY: [External genitalia, male]; Micropenis; Hypoplastic scrotum; [Internal genitalia, male]; Cryptorchidism; [Bladder]; Vesicoureteric reflux (less common)

SKELETAL: [Skull]; Craniosynostosis (reported in 1 patient); [Limbs]; Limited elbow extension; [Hands]; Clinodactyly; Syndactyly; [Feet]; Clinodactyly; Syndactyly

SKIN, NAILS, HAIR: [Hair]; Low posterior hairline; [Nails]; Nail hypoplasia

NEUROLOGIC: [Central nervous system]; Hypotonia; Seizures; Developmental delay, variable; Mental retardation; Wide-based gait; Vestibular anomalies (less common); Speech and language delay; Learning difficulties; [Behavioral/psychiatric manifestations]; Aggressive behavior; Hyperactivity; Poor attention span; Affectionate behavior

LABORATORY ABNORMALITIES: Cytogenetic d...