Ataxia, and Lymphedema

Autosomal dominant cerebellar ataxia, deafness and narcolepsy (ADCA-DN) is a polymorphic disorder and a subtype of autosomal dominant cerebellar ataxia type 1 (ADCA type 1; see this term) characterized by ataxia, sensorineural deafness and narcolepsy with cataplexy and dementia.

AUTOSOMAL DOMINANT CEREBELLAR ATAXIA-DEAFNESS-NARCOLEPSY SYNDROME Is also known as adca-dn syndrome

• Hearing impairment
• Ataxia
• Nystagmus
• Sensorineural hearing impairment
• Cataract

SOURCES: ORPHANET OMIM MENDELIAN

Takenouchi-Kosaki syndrome is a highly heterogeneous autosomal dominant complex congenital developmental disorder affecting multiple organ systems. The core phenotype includes delayed psychomotor development with variable intellectual disability, dysmorphic facial features, and cardiac, genitourinary, and hematologic or lymphatic defects, including thrombocytopenia and lymphedema. Additional features may include abnormalities on brain imaging, skeletal anomalies, and recurrent infections. Some patients have a milder disease course reminiscent of Noonan syndrome (see, e.g., NS1, {163950}) (summary by Martinelli et al., 2018).

MACROTHROMBOCYTOPENIA-LYMPHEDEMA-DEVELOPMENTAL DELAY-FACIAL DYSMORPHISM-CAMPTODACTYLY SYNDROME Is also known as takenouchi-kosaki syndrome|macrothrombocytopenia and mental retardation syndrome

• Intellectual disability
• Seizures
• Global developmental delay
• Generalized hypotonia
• Hearing impairment

SOURCES: OMIM ORPHANET MENDELIAN

Oculodentodigital dysplasia (ODDD) is characterized by craniofacial, neurologic, limb and ocular abnormalities.

OCULODENTODIGITAL DYSPLASIA Is also known as meyer-schwickerath syndrome|odd syndrome|oculodentoosseous dysplasia|odod|oddd syndrome

• Intellectual disability
• Seizures
• Hearing impairment
• Microcephaly
• Ataxia

SOURCES: OMIM ORPHANET MENDELIAN

Weaver syndrome comprises pre- and postnatal overgrowth, accelerated osseous maturation, characteristic craniofacial appearance, and developmental delay. Most cases are sporadic, although autosomal dominant inheritance has been reported. Although there is phenotypic overlap between Weaver syndrome and Sotos syndrome (OMIM ), distinguishing features of Weaver syndrome include broad forehead and face, ocular hypertelorism, prominent wide philtrum, micrognathia, deep horizontal chin groove, and deep-set nails. In addition, carpal bone development is advanced over the rest of the hand in Weaver syndrome, whereas in Sotos syndrome carpal bone development is at or behind that of the rest of the hand (summary by Basel-Vanagaite, 2010).The 'Weaver-like' syndrome reported by Stoll et al. (1985) in a mother and son may be a separate entity.Sotos syndrome (OMIM ), which shows considerable phenotypic overlap with Weaver syndrome, is caused by mutation in the NSD1 gene (OMIM ) on chromosome 5q35.

WEAVER SYNDROME; WVS Is also known as weaver-smith syndrome|wss

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

SOURCES: OMIM MENDELIAN

Cardiofaciocutaneous (CFC) syndrome is a RASopathy characterized by craniofacial dysmorphology, congenital heart disease, dermatological abnormalities (most commonly hyperkeratotic skin and sparse, curly hair), growth retardation and intellectual disability.

CARDIOFACIOCUTANEOUS SYNDROME Is also known as cfcs|cfc syndrome

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

SOURCES: ORPHANET OMIM MENDELIAN

SOTOS SYNDROME 1; SOTOS1 Is also known as chromosome 5q35 deletion syndrome|sotos syndrome|cerebral gigantism

• Intellectual disability
• Seizures
• Global developmental delay
• Generalized hypotonia
• Hearing impairment

SOURCES: OMIM MENDELIAN

Noonan syndrome (NS) is an autosomal dominant disorder characterized by short stature, facial dysmorphism, and a wide spectrum of congenital heart defects. The distinctive facial features consist of a broad forehead, hypertelorism, downslanting palpebral fissures, a high-arched palate, and low-set, posteriorly rotated ears. Cardiac involvement is present in up to 90% of patients. Pulmonic stenosis and hypertrophic cardiomyopathy are the most common forms of cardiac disease, but a variety of other lesions are also observed. Additional relatively frequent features include multiple skeletal defects (chest and spine deformities), webbed neck, mental retardation, cryptorchidism, and bleeding diathesis (summary by Tartaglia et al., 2002). Genetic Heterogeneity of Noonan SyndromeSee also NS3 (OMIM ), caused by mutation in the KRAS gene (OMIM ); NS4 (OMIM ), caused by mutation in the SOS1 gene (OMIM ); NS5 (OMIM ), caused by mutation in the RAF1 gene (OMIM ); NS6 (OMIM ), caused by mutation in the NRAS gene (OMIM ); NS7 (OMIM ), caused by mutation in the BRAF gene (OMIM ); NS8 (OMIM ), caused by mutation in the RIT1 gene (OMIM ); NS9 (OMIM ), caused by mutation in the SOS2 gene (OMIM ); and NS10 (OMIM ), caused by mutation in the LZTR1 gene (OMIM ).See also NS2 (OMIM ) for a possible autosomal recessive form of NS; Noonan syndrome-like disorder with loose anagen hair-1 (NSLH1 ), caused by mutation in the SHOC2 gene (OMIM ); Noonan syndrome-like disorder with loose anagen hair-2 (NSLH2 ), caused by mutation in the PPP1CB gene (OMIM ); and Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia (NSLL ), caused by mutation in the CBL gene (OMIM ).Mutations in the neurofibromin gene (NF1 ), which is the site of mutations causing classic neurofibromatosis type I (NF1 ), have been found in neurofibromatosis-Noonan syndrome (NFNS ).

NOONAN SYNDROME 1; NS1 Is also known as female pseudo-turner syndrome|male turner syndrome|noonan syndrome|turner phenotype with normal karyotype

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

SOURCES: OMIM MENDELIAN

Lissencephaly syndrome, Norman-Roberts type is characterised by the association of lissencephaly type I with craniofacial anomalies (severe microcephaly, a low sloping forehead, a broad and prominent nasal bridge and widely set eyes) and postnatal growth retardation.

LISSENCEPHALY SYNDROME, NORMAN-ROBERTS TYPE Is also known as norman-roberts syndrome|lissencephaly syndrome, norman-roberts type|microlissencephaly type a

• Intellectual disability
• Seizures
• Generalized hypotonia
• Microcephaly
• Growth delay

SOURCES: ORPHANET OMIM MENDELIAN

Alpha-N-acetylgalactosaminidase (NAGA) deficiency type 1 is a very rare and severe type of NAGA deficiency (see this term) characterized by infantile neuroaxonal dystrophy.

ALPHA-N-ACETYLGALACTOSAMINIDASE DEFICIENCY TYPE 1 Is also known as schindler disease type 1|naga deficiency type 1

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

SOURCES: ORPHANET MENDELIAN

Autosomal recessive chorioretinopathy-microcephaly syndrome is a rare neuro-opthalmological disease characterized by severe microcephaly of prenatal onset (with diminutive anterior fontanelle and sutural ridging), growth retardation, global developmental delay and intellectual disability (ranging from mild to profound), dysmorphic features (sloping forehead, micro/retrognathia, prominent ears) and visual impairments (including microphthalmia to anophtalmia, generalized retinopathy or multiple punched-out retinal lesions, retinal folds with retinal detachment, optic nerve hypoplasia, strabismus, nystagmus). Brain MRI may show reduced cortical size, cerebral hemispheres, corpus callosum, pachygyria, symplified gyral folding or normal pattern. Other associated features include epilepsy and neurological deficits.

AUTOSOMAL RECESSIVE CHORIORETINOPATHY-MICROCEPHALY SYNDROME Is also known as autosomal recessive chorioretinopathy-microcephaly-intellectual disability syndrome

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

SOURCES: ORPHANET OMIM MENDELIAN