Cognitive impairment, and Hypogonadism

Medium match BARDET-BIEDL SYNDROME 10; BBS10

BBS10 is characterized by progressive retinal dystrophy, obesity, polydactyly, cognitive impairment, and renal dysplasia (Stoetzel et al., 2006). BBS10 represents a major locus for BBS, with mutations in the BBS10 gene accounting for approximately 20% of BBS patients (Stoetzel et al., 2006; Zaghloul and Katsanis, 2009).For a general phenotypic description and a discussion of genetic heterogeneity of Bardet-Biedl syndrome, see BBS1 (OMIM ).

• Cognitive impairment
• Renal insufficiency
• Obesity
• Rod-cone dystrophy
• Hypogonadism

SOURCES: OMIM MENDELIAN

Medium match BARDET-BIEDL SYNDROME 4; BBS4

BBS4 is a rare multisystemic disorder characterized primarily by retinal dystrophy, obesity, polydactyly, and renal dysfunction that accounts for less than 3% of BBS (Katsanis et al., 2002). Anosmia has been described in patients with BBS4 (Iannaccone et al., 2005), as well as polydactyly confined to the hands (Carmi et al., 1995).For a general phenotypic description and a discussion of genetic heterogeneity of Bardet-Biedl syndrome, see BBS1 (OMIM ).

• Intellectual disability
• Cryptorchidism
• Cognitive impairment
• Brachydactyly
• Blindness

SOURCES: OMIM MENDELIAN

Low match BARDET-BIEDL SYNDROME 5; BBS5

BBS5 is a ciliopathy associated with severe and early-onset retinal dystrophy, postaxial polydactyly, obesity, renal dysfunction, hypogonadism, and learning difficulties (summary by Scheidecker et al., 2015). Patients described by Young et al. (1999) and Moore et al. (2005) with mutations in the BBS5 gene did not have polydactyly. The contribution of BBS5 mutations to all cases of BBS has been estimated at 2% (Li et al., 2004) and 0.40% (Zaghloul and Katsanis, 2009).For a general phenotypic description and a discussion of genetic heterogeneity of Bardet-Biedl syndrome, see BBS1 (OMIM ).

• Cognitive impairment
• Visual impairment
• Brachydactyly
• Syndactyly
• Obesity

SOURCES: OMIM MENDELIAN

Low match BARDET-BIEDL SYNDROME 2; BBS2

BBS2 is an autosomal recessive ciliopathy characterized by retinal degeneration, polydactyly, renal disease, hypogonadism, obesity, dysmorphic features, and variable degrees of cognitive impairment (Innes et al., 2010). Mutation in the BBS2 gene is the third most frequent cause of BBS, accounting for approximately 8% of cases (Zaghloul and Katsanis, 2009).For a general phenotypic description and a discussion of genetic heterogeneity of Bardet-Biedl syndrome, see BBS1 (OMIM ).

• Intellectual disability
• Global developmental delay
• Cognitive impairment
• Cardiomyopathy
• Atrial septal defect

SOURCES: OMIM MENDELIAN

Low match CEREBELLAR ATAXIA-HYPOGONADISM SYNDROME

Cerebellar ataxia-hypogonadism syndrome is a very rare autosomal recessive neurodegenerative disorder characterized by the combination of progressive cerebellar ataxia with onset from early childhood to the fourth decade, and hypogonadotropic hypogonadism (delayed puberty and lack of secondary sex characteristics). Cerebellar ataxia-hypogonadism syndrome belongs to a clinical continuum of neurodegenerative disorders along with clinically overlapping disorders such as ataxia-hypogonadism-choroidal dystrophy syndrome (see this term).

CEREBELLAR ATAXIA-HYPOGONADISM SYNDROME Is also known as luteinizing hormone-releasing hormone deficiency with ataxia|gordon-holmes syndrome

• Short stature
• Ataxia
• Nystagmus
• Muscular hypotonia
• Optic atrophy

SOURCES: ORPHANET MENDELIAN

Low match BOUCHER-NEUHAUSER SYNDROME; BNHS

Boucher-Neuhauser syndrome is an autosomal recessive disorder characterized classically by the triad of spinocerebellar ataxia, hypogonadotropic hypogonadism, and visual impairment due to chorioretinal dystrophy. The age at onset is variable, but most patients develop one or more symptoms in the first decade of life. Chorioretinal dystrophy may not always be present. BNHS is part of a spectrum of neurodegenerative diseases associated with mutations in the PNPLA6 gene that also includes spastic paraplegia-39 (SPG39 ) (summary by Synofzik et al., 2014).See also Gordon Holmes syndrome (GDHS ), caused by mutation in the RNF216 gene (OMIM ), which is also characterized by the combination of cerebellar ataxia and hypogonadotropic hypogonadism.

BOUCHER-NEUHAUSER SYNDROME; BNHS Is also known as spinocerebellar ataxia, hypogonadotropic hypogonadism, and chorioretinal dystrophy

• Ataxia
• Spasticity
• Cognitive impairment
• Visual impairment
• Dysarthria

SOURCES: OMIM MENDELIAN

Low match BARDET-BIEDL SYNDROME 8; BBS8

BBS8 is an autosomal recessive disorder characterized by retinitis pigmentosa, obesity, postaxial polydactyly, hypogonadism, and developmental delay (Ansley et al., 2003).For a general phenotypic description and a discussion of genetic heterogeneity of Bardet-Biedl syndrome, see BBS1 (OMIM ).

• Intellectual disability
• Global developmental delay
• Hearing impairment
• Cognitive impairment
• Obesity

SOURCES: OMIM MENDELIAN

Low match LEUKODYSTROPHY, HYPOMYELINATING, 8, WITH OR WITHOUT OLIGODONTIA AND/OR HYPOGONADOTROPIC HYPOGONADISM; HLD8

Hypomyelinating leukodystrophy-8 is an autosomal recessive neurologic disorder characterized by early childhood onset of cerebellar ataxia and mild intellectual disabilities associated with diffuse hypomyelination apparent on brain MRI. Variable features include oligodontia and/or hypogonadotropic hypogonadism (summary by Tetreault et al., 2011).See also HLD7 (OMIM ), which has similar features and is caused by mutation in the POLR3A gene (OMIM ) on chromosome 10q22. The POLR3A and POLR3B genes encode the 2 largest subunits of RNA polymerase III.For a general phenotypic description and a discussion of genetic heterogeneity of hypomyelinating leukodystrophy, see {312080}.

• Intellectual disability
• Short stature
• Generalized hypotonia
• Ataxia
• Nystagmus

SOURCES: OMIM MENDELIAN

Low match GORDON HOLMES SYNDROME; GDHS

Gordon Holmes syndrome is an autosomal recessive adult-onset neurodegenerative disorder characterized by progressive cognitive decline, dementia, and variable movement disorders, such as ataxia and chorea. The neurologic phenotype is associated with hypogonadotropic hypogonadism (summary by Santens et al., 2015).

GORDON HOLMES SYNDROME; GDHS Is also known as cahh|cerebellar ataxia and hypogonadotropic hypogonadism|luteinizing hormone-releasing hormone, deficiency of, with ataxia|lhrh deficiency and ataxia

• Hearing impairment
• Ataxia
• Dysarthria
• Abnormality of the skeletal system
• Cerebellar atrophy

SOURCES: OMIM MENDELIAN

Low match KERATODERMA HEREDITARIUM MUTILANS

Keratoderma hereditarium mutilans is a rare, diffuse, mutilating, hereditary palmoplantar keratoderma disorder characterized by severe, honeycomb-pattern palmoplantar keratosis and pseudoainhum of the digits leading to autoamputation, associated with mild to moderate congenital sensorineural hearing loss. Additional features include stellate keratosis on the extensor surfaces of the fingers, feet, elbows and knees. Alopecia, onychogryphosis, nail dystrophy or clubbing, spastic paraplegia and myopathy may also be associated.

KERATODERMA HEREDITARIUM MUTILANS Is also known as khm|mutilating keratoderma|deafness, congenital, with keratopachydermia and constrictions of fingers and toes|vohwinkel syndrome|mutilating keratoderma of vohwinkel|mutilating keratoderma plus deafness|keratoderma hereditarium mutilans|ppk mutilans and de

• Hearing impairment
• Microcephaly
• Sensorineural hearing impairment
• Cleft palate
• Cognitive impairment

SOURCES: OMIM ORPHANET MESH MENDELIAN