Delayed speech and language development, and Cone/cone-rod dystrophy

High match BARDET-BIEDL SYNDROME 21; BBS21

BBS21 is an autosomal recessive ciliopathy characterized by obesity, postaxial polydactyly, retinal degeneration, and mild cognitive impairment (Heon et al., 2016; Khan et al., 2016).For a general phenotypic description and a discussion of genetic heterogeneity of Bardet-Biedl syndrome, see BBS1 (OMIM ).

• Autosomal recessive inheritance
• Delayed speech and language development
• Myopia
• Blindness
• Abnormality of the dentition

SOURCES: UMLS MONDO OMIM

High match PONTOCEREBELLAR HYPOPLASIA, TYPE 1B; PCH1B

Pontocerebellar hypoplasia type 1B is a severe autosomal recessive neurologic disorder characterized by a combination of cerebellar and spinal motor neuron degeneration beginning at birth. There is diffuse muscle weakness, progressive microcephaly, global developmental delay, and brainstem involvement (summary by Wan et al., 2012). PCH1B can be divided into mild, moderate, and severe subgroups that vary in age at onset, progression, clinical and neuroradiologic severity, and survival (summary by Halevy et al., 2014).For a phenotypic description and a discussion of genetic heterogeneity of PCH, see PCH1A (OMIM ).

• Autosomal recessive inheritance
• Intellectual disability
• Seizures
• Global developmental delay
• Generalized hypotonia

SOURCES: MONDO OMIM DOID UMLS

Medium match BARDET-BIEDL SYNDROME 17; BBS17

BBS17 is an autosomal recessive ciliopathy characterized by retinitis pigmentosa, cognitive impairment, obesity, renal dysfunction, and hypogenitalism. Polydactyly, most often postaxial, is also a primary feature of BBS; in BBS17 mesoaxial polydactyly, with fused or Y-shaped metacarpals, is a distinct manifestation (Deffert et al., 2007; Schaefer et al., 2014).For a general phenotypic description and a discussion of genetic heterogeneity of Bardet-Biedl syndrome, see BBS1 (OMIM ).

• Autosomal recessive inheritance
• Global developmental delay
• Cognitive impairment
• Brachydactyly
• Renal insufficiency

SOURCES: UMLS DOID OMIM MONDO

Medium match SPINOCEREBELLAR ATAXIA 7; SCA7

Spinocerebellar ataxia-7 (SCA7) is an autosomal dominant neurodegenerative disorder characterized by adult onset of progressive cerebellar ataxia associated with pigmental macular dystrophy. In her classification of ataxia, Harding (1982) referred to progressive cerebellar ataxia with pigmentary macular degeneration as type II ADCA (autosomal dominant cerebellar ataxia). The age at onset, degree of severity, and rate of progression vary among and within families. Associated neurologic signs, such as ophthalmoplegia, pyramidal or extrapyramidal signs, deep sensory loss, or dementia, are also variable. Genetic anticipation is observed and is greater in paternal than in maternal transmissions (Benomar et al., 1994; summary by David et al., 1996).For a general discussion of autosomal dominant spinocerebellar ataxia, see SCA1 (OMIM ).

SPINOCEREBELLAR ATAXIA 7; SCA7 Is also known as olivopontocerebellar atrophy iii;opca3, opca iii, opca with retinal degeneration, opca with macular degeneration and external ophthalmoplegia, autosomal dominant cerebellar ataxia, type ii, adca, type ii;ataxia with pigmentary retinopathy; cerebellar syndrome-pigmentary maculopathy syndrome; sca7

• Autosomal dominant inheritance
• Global developmental delay
• Generalized hypotonia
• Ataxia
• Nystagmus

SOURCES: DOID GARD ORPHANET MONDO SCTID UMLS OMIM NCIT

Medium match LEBER CONGENITAL AMAUROSIS 1; LCA1

Leber congenital amaurosis comprises a group of early-onset childhood retinal dystrophies characterized by vision loss, nystagmus, and severe retinal dysfunction. Patients usually present at birth with profound vision loss and pendular nystagmus. Electroretinogram (ERG) responses are usually nonrecordable. Other clinical findings may include high hypermetropia, photodysphoria, oculodigital sign, keratoconus, cataracts, and a variable appearance to the fundus (summary by Chung and Traboulsi, 2009). Genetic Heterogeneity of Leber Congenital AmaurosisLCA2 (OMIM ) is caused by mutation in the RPE65 gene (RPE65 ) on chromosome 1p31. LCA3 (OMIM ) is caused by mutation in the SPATA7 gene (OMIM ) on chromosome 14q31.3. LCA4 (OMIM ) is caused by mutation in the AIPL1 gene (OMIM ) on chromosome 17p13.1. LCA5 (OMIM ) is caused by mutation in the LCA5 gene (OMIM ) on chromosome 6q14.1. LCA6 (OMIM ) is caused by mutation in the RPGRIP1 gene (OMIM ) on chromosome 14q11. LCA7 (OMIM ) is caused by mutation in the CRX gene (OMIM ) on chromosome 19q13.3. LCA8 (OMIM ) is caused by mutation in the CRB1 gene (OMIM ) on chromosome 1q31-q32. LCA9 (OMIM ) is a locus that has been mapped to chromosome 1p36. LCA10 (OMIM ) is caused by mutation in the CEP290 gene (OMIM ) on chromosome 12q21 and may account for as many as 21% of cases of LCA. LCA11 (OMIM ) is caused by mutation in the IMPDH1 gene (OMIM ) on chromosome 7q31.3-q32. LCA12 (OMIM ) is caused by mutation in the RD3 gene (OMIM ) on chromosome 1q32.3. LCA13 (OMIM ) is caused by mutation in the RDH12 gene (OMIM ) on chromosome 14q24.1. LCA14 (OMIM ) is caused by mutation in the LRAT gene (OMIM ) on chromosome 4q31. LCA15 (OMIM ) is caused by mutation in the TULP1 gene (OMIM ) on chromosome 6p21.3. LCA16 (OMIM ) is caused by mutation in the KCNJ13 gene (OMIM ) on chromosome 2q37. LCA17 (OMIM ) is caused by mutation in the GDF6 gene (OMIM ) on chromosome 8q22. LCA18 (see {608133}) is caused by mutation in the PRPH2 gene (OMIM ) on chromosome 6p21.Perrault et al. (1999) provided a review of Leber congenital amaurosis, with emphasis on genetic heterogeneity.Wiszniewski et al. (2011) analyzed 13 known LCA genes in 60 LCA probands, and identified homozygous or compound heterozygous mutations in 42 (70%). In addition, a third disease-associated mutant allele at a second locus was identified in 7 (12%) of the 60 patients. Wiszniewski et al. (2011) stated that the significance of the third mutated allele was unknown, but suggested that mutational load might be important to penetrance of the LCA phenotype.Because LCA manifests very early in life and results in profound vision loss, patients with mutations in other syndromic or nonsyndromic eye disease genes may receive an initial diagnosis of LCA, prior to development of syndromic features or before more thorough phenotyping can be performed (see, e.g., Senior-Loken syndrome-5, {609254}).

LEBER CONGENITAL AMAUROSIS 1; LCA1 Is also known as amaurosis congenita of leber i, lca, retinal blindness, congenital;crb;amaurosis congenita of leber

• Autosomal recessive inheritance
• Intellectual disability
• Seizures
• Global developmental delay
• Hearing impairment

SOURCES: DOID GARD MONDO UMLS ORPHANET OMIM

Medium match THIAMINE-RESPONSIVE MEGALOBLASTIC ANEMIA SYNDROME; TRMA

Thiamine-responsive megaloblastic anemia syndrome comprises megaloblastic anemia, diabetes mellitus, and sensorineural deafness. Onset is typically between infancy and adolescence, but all of the cardinal findings are often not present initially. The anemia, and sometimes the diabetes, improves with high doses of thiamine. Other more variable features include optic atrophy, congenital heart defects, short stature, and stroke (summary by Bergmann et al., 2009). Genetic Heterogeneity of Disorders Due to Thiamine Metabolism DysfunctionSee also episodic encephalopathies due to defects in thiamine metabolism: biotin-responsive basal ganglia disease (THMD2 ), caused by mutation in the SLC19A3 gene (OMIM ) on chromosome 2q36; Amish lethal microcephaly (THMD3 ) and bilateral striatal necrosis and progressive polyneuropathy (THMD4 ), both caused by mutation in the SLC25A19 gene (OMIM ) on chromosome 17q25; and THMD5 (OMIM ), caused by mutation in the TPK1 gene (OMIM ) on chromosome 7q35.

THIAMINE-RESPONSIVE MEGALOBLASTIC ANEMIA SYNDROME; TRMA Is also known as thiamine metabolism dysfunction syndrome 1 (megaloblastic anemia, diabetes mellitus, and deafness type);thmd1, megaloblastic anemia, thiamine-responsive, with diabetes mellitus and sensorineural deafness, rogers syndrome, thiamine-responsive anemia syndrome, thiamine-responsive myelodysplasia;rogers syndrome; trma; thiamine-responsive megaloblastic anemia with diabetes mellitus and sensorineural deafness

• Autosomal recessive inheritance
• Seizures
• Global developmental delay
• Short stature
• Pica

SOURCES: OMIM DOID ICD10 ORPHANET UMLS MONDO SCTID GARD MESH

Medium match WHITE-SUTTON SYNDROME; WHSUS

Intellectual disability-microcephaly-strabismus-behavioral abnormalities syndrome is a rare, genetic, syndromic intellecutal disability disorder characterized by craniofacial dysmorphism (microcephaly, hypotonic facies, strabismus, long and flat malar region, posteriorly rotated ears, flat nasal bridge with broad nasal tip, short philtrum, thin vermillion border, open mouth with down-turned corners, high arched palate, pointed chin), global developmental delay, intellectual disability and variable neurobehavioral abnormalities (autism spectrum disorder, aggressivness, self injury). Additional features include vision abnormalities and variable sensorineural hearing loss, as well as short stature, hypotonia and gastrointestinal manifestations (e.g. poor feeding, gastroesophageal reflux, constipation).

WHITE-SUTTON SYNDROME; WHSUS Is also known as mental retardation, autosomal dominant 37;mrd37;

• Autosomal dominant inheritance
• Intellectual disability
• Seizures
• Global developmental delay
• Short stature

SOURCES: EFO UMLS OMIM ORPHANET MONDO DOID

Medium match ALSTROM SYNDROME; ALMS

Alstrom syndrome is an autosomal recessive disorder characterized by progressive cone-rod dystrophy leading to blindness, sensorineural hearing loss, childhood obesity associated with hyperinsulinemia, and type 2 diabetes mellitus. Dilated cardiomyopathy occurs in approximately 70% of patients during infancy or adolescence. Renal failure, pulmonary, hepatic, and urologic dysfunction are often observed, and systemic fibrosis develops with age (summary by Collin et al., 2002; Marshall et al., 2007).

ALSTROM SYNDROME; ALMS Is also known as alss;

• Autosomal recessive inheritance
• Intellectual disability
• Seizures
• Global developmental delay
• Short stature

SOURCES: GARD NCIT DOID SCTID UMLS OMIM MONDO MESH ORPHANET

Medium match RETINITIS PIGMENTOSA 69; RP69

Retinitis pigmentosa (RP), also designated rod-cone dystrophy, is characterized by initial night blindness due to rod dysfunction, with subsequent progressive constriction of visual fields, abnormal color vision, and eventual loss of central vision due to cone photoreceptor involvement (summary by El Shamieh et al., 2014).For a discussion of genetic heterogeneity of retinitis pigmentosa, see {268000}.

• Autosomal recessive inheritance
• Intellectual disability
• Pica
• Blindness
• Rod-cone dystrophy

SOURCES: MONDO DOID OMIM UMLS

Medium match RETINITIS PIGMENTOSA 3; RP3

X-linked retinitis pigmentosa (XLRP) is a severe form of inherited retinal degeneration that primarily affects the rod photoreceptors (Demirci et al., 2002). It typically causes an early-onset night blindness and loss of peripheral vision, often causing patients to become legally blind by the age of 30 to 40 years. In RP3, affected males have a severe phenotype, and carrier females show a wide spectrum of clinical features ranging from completely asymptomatic to severe RP (Jin et al., 2007). Mutation in the RPGR gene is believed to account for approximately 70% of XLRP (Vervoort et al., 2000).For a discussion of genetic heterogeneity of retinitis pigmentosa, see {268000}.

RETINITIS PIGMENTOSA 3; RP3 Is also known as retinitis pigmentosa 15;rp15, cone-rod degeneration, x-linked, choroidoretinal degeneration with retinal reflex in heterozygous women

• Intellectual disability
• Pica
• Visual impairment
• Myopia
• Optic atrophy

SOURCES: UMLS OMIM