Muscle weakness, and Microcornea

Axenfeld-Rieger syndrome is an autosomal dominant disorder of morphogenesis that results in abnormal development of the anterior segment of the eye, and results in blindness from glaucoma in approximately 50% of affected individuals (Fitch and Kaback, 1978). Systemic anomalies are associated, including dental hypoplasia, failure of involution of periumbilical skin, and maxillary hypoplasia (Alkemade, 1969). Genetic Heterogeneity of Axenfeld-Rieger SyndromeLinkage studies indicate that a second type of Axenfeld-Rieger syndrome maps to chromosome 13q14 (RIEG2 ). A third form of Axenfeld-Rieger syndrome (RIEG3 ) is caused by mutation in the FOXC1 gene (OMIM ) on chromosome 6p25.See {109120} for a form of Axenfeld-Rieger syndrome associated with partially absent eye muscles, hydrocephalus, and skeletal abnormalities.

AXENFELD-RIEGER SYNDROME, TYPE 1; RIEG1 Is also known as rieger syndrome, type 1|rgs|rieg

• Intellectual disability
• Global developmental delay
• Short stature
• Hearing impairment
• Scoliosis

SOURCES: OMIM MENDELIAN

Ehlers-Danlos syndrome, kyphoscoliotic and deafness type is a form of Ehlers-Danlos syndrome, characterized by severe generalized hypotonia at birth with severe early-onset kyphoscolosis along with joint hypermobility (without contractures) leading to recurrent dislocations, and sensorineural hearing impairment.

EHLERS-DANLOS SYNDROME, KYPHOSCOLIOTIC AND DEAFNESS TYPE Is also known as ehlers-danlos syndrome with progressive kyphoscoliosis, myopathy, and hearing loss|ehlers-danlos syndrome with progressive kyphoscoliosis, myopathy, and deafness|edskmh|eds with progressive kyphoscoliosis, myopathy, and deafness|eds, kyphoscoliotic and he

• Generalized hypotonia
• Hearing impairment
• Scoliosis
• Sensorineural hearing impairment
• Muscle weakness

SOURCES: OMIM ORPHANET MENDELIAN

COL4A1-related familial vascular leukoencephalopathy is a rare, genetic, neurological disease characterized by the presence of fragile small-vessel intracerebral vasculature in various members of a single family, manifesting, clinically, with single or recurrent hemorrhagic and/or ischemic stroke and, frequently, ocular and renal involvement. Neuroimaging reveals diffuse, periventricular leukoencephalopathy associated with dilated perivascular spaces, lacunar infarction and microhemorrhages.

COL4A1-RELATED FAMILIAL VASCULAR LEUKOENCEPHALOPATHY Is also known as col4a1-related brain small vessel disease with hemorrhage|leukoencephalopathy with axenfeld-rieger anomaly|brain small vessel disease with axenfeld-rieger anomaly|brain small vessel disease with hemorrhage|infantile hemiparesis|retinal arteriolar tortuosi

• Seizures
• Global developmental delay
• Hearing impairment
• Microcephaly
• Nystagmus

SOURCES: ORPHANET MESH OMIM MENDELIAN

Oculocerebrofacial syndrome, Kaufman type is characterized by psychomotor retardation, microcephaly, upslanting palpebral fissures, eye abnormalities (microcornea, strabismus, myopia, optic atrophy), high-arched palate, preauricular skin tags and micrognathia with respiratory distress. It has been described in about 10 cases. Other anomalies can be present: long thin hands and feet, ambiguous genitalia, hypertelorism, etc. An autosomal recessive mode of inheritance seems most likely.

OCULOCEREBROFACIAL SYNDROME, KAUFMAN TYPE Is also known as mendenhall syndrome|rabson-mendenhall syndrome

• Intellectual disability
• Global developmental delay
• Short stature
• Microcephaly
• Growth delay

SOURCES: OMIM ORPHANET MENDELIAN

Walker-Warburg Syndrome (WWS) is a rare form of congenital muscular dystrophy associated with brain and eye abnormalities.

WALKER-WARBURG SYNDROME Is also known as hard syndrome|cerebroocular dysplasia-muscular dystrophy syndrome|hydrocephalus, agyria, and retinal dysplasia|walker-warburg syndrome or muscle-eye-brain disease, pomt1-related|wws|hydrocephalus-agyria-retinal dysplasia syndrome|cod-md syndrome

• Intellectual disability
• Seizures
• Global developmental delay
• Generalized hypotonia
• Microcephaly

SOURCES: ORPHANET OMIM MENDELIAN

Duane-radial ray syndrome, also known as Okihiro syndrome, is an autosomal dominant disorder characterized by upper limb anomalies, ocular anomalies, and, in some cases, renal anomalies. The combination of the 3 findings was earlier referred to as 'acro-renal-ocular syndrome.' The ocular anomalies usually include Duane anomaly (see {126800}), but this finding may be absent in some patients (Kohlhase et al., 2003). Similarly, renal anomalies are not always seen and may not have been investigated, particularly in cases reported before routine renal imaging (Aalfs et al., 1996). Other less common features include sensorineural deafness and gastrointestinal anomalies, such as imperforate anus.The Holt-Oram syndrome (OMIM ), caused by mutation in the TBX5 gene (OMIM ) on chromosome 12q24, shows similar anomalies of the upper limb, but can be differentiated from Duane-radial ray syndrome by the absence of ocular and renal anomalies and the presence of severe congenital heart defects (Kohlhase, 2003).

DUANE-RADIAL RAY SYNDROME; DRRS Is also known as dr syndrome|acrorenoocular syndrome|duane anomaly with radial ray abnormalities and deafness|okihiro syndrome

• Hearing impairment
• Scoliosis
• Hypertelorism
• Strabismus
• Sensorineural hearing impairment

SOURCES: ORPHANET OMIM MENDELIAN

Congenital Cataracts Facial Dysmorphism Neuropathy (CCFDN) syndrome is a complex developmental disorder of autosomal recessive inheritance.

CONGENITAL CATARACTS-FACIAL DYSMORPHISM-NEUROPATHY SYNDROME Is also known as ccfdn|cataract, congenital, with facial dysmorphism and neuropathy

• Intellectual disability
• Global developmental delay
• Short stature
• Hearing impairment
• Scoliosis

SOURCES: OMIM MESH ORPHANET MENDELIAN

Warburg Micro syndrome is a rare autosomal recessive syndrome characterized by microcephaly, microphthalmia, microcornea, congenital cataracts, optic atrophy, cortical dysplasia, in particular corpus callosum hypoplasia, severe mental retardation, spastic diplegia, and hypogonadism (summary by Morris-Rosendahl et al., 2010). Genetic Heterogeneity of Warburg Micro SyndromeWarburg Micro syndrome-2 (WARBM2 ) is caused by mutation in the RAB3GAP2 gene (OMIM ) on chromosome 1q41. WARBM3 (OMIM ) is caused by mutation in the RAB18 gene (OMIM ) on chromosome 10p12. WARBM4 (OMIM ) is caused by mutation in the TBC1D20 gene (OMIM ) on chromosome 20p13.See also Martsolf syndrome (OMIM ), a clinically overlapping but milder autosomal recessive disorder caused by autosomal recessive mutation in the RAB3GAP2 gene.Handley et al. (2013) provided an overview of the disease variants identified in the RAB3GAP1, RAB3GAP2, and RAB18 genes, noting that a total of 144 families with WARBM and 9 families with Martsolf syndrome had been studied. Mutations were identified in RAB3GAP1 in 41% of cases, in RAB3GAP2 in 7% of cases, and in RAB18 in 5% of cases. Although RAB18 had not been linked to RAB3 pathways, Handley et al. (2013) stated that mutations in all 3 genes cause an indistinguishable phenotype, making it likely that there is some functional overlap.

WARBURG MICRO SYNDROME 1; WARBM1 Is also known as micro syndrome

• Intellectual disability
• Seizures
• Global developmental delay
• Short stature
• Generalized hypotonia

SOURCES: OMIM MENDELIAN

SCHWARTZ-JAMPEL SYNDROME, TYPE 1; SJS1 Is also known as sja syndrome|schwartz-jampel-aberfeld syndrome|sjs|myotonic myopathy, dwarfism, chondrodystrophy, and ocular and facial abnormalities|schwartz-jampel syndrome|chondrodystrophic myotonia

• Intellectual disability
• Short stature
• Generalized hypotonia
• Microcephaly
• Growth delay

SOURCES: OMIM MENDELIAN

Marinesco-Sjögren syndrome (MSS) belongs to the group of autosomal recessive cerebellar ataxias. Cardinal features of MSS are cerebellar ataxia, congenital cataract, and delayed psychomotor development.

• Intellectual disability
• Seizures
• Global developmental delay
• Short stature
• Generalized hypotonia

SOURCES: ORPHANET OMIM MENDELIAN