Rod-cone dystrophy, and Nephritis

Medium match NEPHRONOPHTHISIS 20; NPHP20

Nephronophthisis-20 is an autosomal recessive tubulointerstitial nephritis characterized by progressive renal fibrosis resulting in end-stage renal failure. The age at onset is relatively late compared to other forms of NPHP, and patients develop end-stage renal disease in the second or third decades. Unlike most other forms of NPHP, NPHP20 does not have features of a ciliopathy and patients do not appear to have extrarenal manifestations (summary by Macia et al., 2017).For a general phenotypic description and a discussion of genetic heterogeneity of nephronophthisis, see NPHP1 (OMIM ).

• Short stature
• Scoliosis
• Abnormal facial shape
• Renal insufficiency
• Rod-cone dystrophy

SOURCES: OMIM MENDELIAN

Medium match SENIOR-LOKEN SYNDROME 9; SLSN9

Senior-Loken syndrome-9 is an autosomal recessive disorder characterized by early-onset nephronophthisis and pigmentary retinopathy. Additional more variable features can include liver defects, skeletal anomalies, and obesity (summary by Bizet et al., 2015).For a phenotypic description and a discussion of genetic heterogeneity of Senior-Loken syndrome, see {266900}.

• Global developmental delay
• Nystagmus
• Strabismus
• Abnormality of the skeletal system
• Obesity

SOURCES: OMIM MENDELIAN

Medium match SENIOR-LOKEN SYNDROME

Senior-Loken syndrome (SLSN) is a very rare autosomal recessive oculo-renal disease characterized by the association of nephronophthisis (NPHP), a chronic kidney disease, with retinal dystrophy.

SENIOR-LOKEN SYNDROME Is also known as renal-retinal syndrome|juvenile nephronophthisis with leber amaurosis|loken-senior syndrome|renal dysplasia-retinal aplasia syndrome|nephronophthisis with retinal dystrophy|slsn|renal dysplasia and retinal aplasia|senior-loken syndrome

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

SOURCES: ORPHANET OMIM MENDELIAN

Medium match COENZYME Q10 DEFICIENCY, PRIMARY, 1; COQ10D1

Primary CoQ10 deficiency is a rare, clinically heterogeneous autosomal recessive disorder caused by mutation in any of the genes encoding proteins directly involved in the synthesis of coenzyme Q (review by Quinzii and Hirano, 2011). Coenzyme Q10 (CoQ10), or ubiquinone, is a mobile lipophilic electron carrier critical for electron transfer by the mitochondrial inner membrane respiratory chain (Duncan et al., 2009).The disorder has been associated with 5 major phenotypes, but the molecular basis has not been determined in most patients with the disorder and there are no clear genotype/phenotype correlations. The phenotypes include an encephalomyopathic form with seizures and ataxia (Ogasahara et al., 1989); a multisystem infantile form with encephalopathy, cardiomyopathy and renal failure (Rotig et al., 2000); a predominantly cerebellar form with ataxia and cerebellar atrophy (Lamperti et al., 2003); Leigh syndrome with growth retardation (van Maldergem et al., 2002); and an isolated myopathic form (Lalani et al., 2005). The correct diagnosis is important because some patients may show a favorable response to CoQ10 treatment. Genetic Heterogeneity of Primary Coenzyme Q10 DeficiencySee also COQ10D2 (OMIM ), caused by mutation in the PDSS1 gene (OMIM ) on chromosome 10p12; COQ10D3 (OMIM ), caused by mutation in the PDSS2 gene (OMIM ) on chromosome 6q21; COQ10D4 (OMIM ), caused by mutation in the COQ8 gene (ADCK3 ) on chromosome 1q42; COQ10D5 (OMIM ), caused by mutation in the COQ9 gene (OMIM ) on chromosome 16q21; COQ10D6 (OMIM ), caused by mutation in the COQ6 gene (OMIM ) on chromosome 14q24; COQ10D7 (OMIM ), caused by mutation in the COQ4 gene (OMIM ) on chromosome 9q34; and COQ10D8 (OMIM ), caused by mutation in the COQ7 gene (OMIM ) on chromosome 16p13.Secondary CoQ10 deficiency has been reported in association with glutaric aciduria type IIC (MADD ), caused by mutation in the ETFDH gene (OMIM ) on chromosome 4q, and with ataxia-oculomotor apraxia syndrome-1 (AOA1 ), caused by mutation in the APTX gene (OMIM ) on chromosome 9p13.

COENZYME Q10 DEFICIENCY, PRIMARY, 1; COQ10D1 Is also known as ubiquinone deficiency 1|coq10 deficiency, primary, 1|coq deficiency 1|coenzyme q deficiency 1

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

SOURCES: OMIM ORPHANET MENDELIAN

Medium match ISOLATED COMPLEX III DEFICIENCY

Isolated complex III deficiency is a rare, genetic, mitochondrial oxidative phosphorylation disorder characterized by a wide spectrum of clinical manifestations ranging from isolated myopathy or transient hepatopathy to severe multisystem disorder (that may include hypotonia, failure to thrive, psychomotor delay, cardiomyopathy, encephalopathy, renal tubulopathy, hearing impairment, lactic acidosis, hypoglycemia and other signs and symptoms).

ISOLATED COMPLEX III DEFICIENCY Is also known as isolated coq-cytochrome c reductase deficiency|isolated ubiquinone-cytochrome c reductase deficiency|isolated mitochondrial respiratory chain complex iii deficiency|isolated coenzyme q-cytochrome c reductase deficiency

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

SOURCES: ORPHANET OMIM MENDELIAN

Medium match SHORT-RIB THORACIC DYSPLASIA 9 WITH OR WITHOUT POLYDACTYLY; SRTD9

Short-rib thoracic dysplasia (SRTD) with or without polydactyly refers to a group of autosomal recessive skeletal ciliopathies that are characterized by a constricted thoracic cage, short ribs, shortened tubular bones, and a 'trident' appearance of the acetabular roof. SRTD encompasses Ellis-van Creveld syndrome (EVC) and the disorders previously designated as Jeune syndrome or asphyxiating thoracic dystrophy (ATD), short rib-polydactyly syndrome (SRPS), and Mainzer-Saldino syndrome (MZSDS). Polydactyly is variably present, and there is phenotypic overlap in the various forms of SRTDs, which differ by visceral malformation and metaphyseal appearance. Nonskeletal involvement can include cleft lip/palate as well as anomalies of major organs such as the brain, eye, heart, kidneys, liver, pancreas, intestines, and genitalia. Some forms of SRTD are lethal in the neonatal period due to respiratory insufficiency secondary to a severely restricted thoracic cage, whereas others are compatible with life (summary by Huber and Cormier-Daire, 2012 and Schmidts et al., 2013).There is phenotypic overlap with the cranioectodermal dysplasias (Sensenbrenner syndrome; see CED1, {218330}).For a discussion of genetic heterogeneity of short-rib thoracic dysplasia, see SRTD1 (OMIM ).

SHORT-RIB THORACIC DYSPLASIA 9 WITH OR WITHOUT POLYDACTYLY; SRTD9 Is also known as mzsds|mainzer-saldino syndrome|renal dysplasia, retinal pigmentary dystrophy, cerebellar ataxia, and skeletal dysplasia|conorenal syndrome

• Seizures
• Global developmental delay
• Short stature
• Microcephaly
• Ataxia

SOURCES: OMIM MENDELIAN

Medium match ALSTRÖM SYNDROME

Alström syndrome (AS) is a multisystemic disorder characterized by cone-rod dystrophy, hearing loss, obesity, insulin resistance and hyperinsulinemia, type 2 diabetes mellitus, dilated cardiomyopathy (DCM; see this term), and progressive hepatic and renal dysfunction.

ALSTRÖM SYNDROME Is also known as alss

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

SOURCES: OMIM ORPHANET MESH MENDELIAN

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

Low match BARDET-BIEDL SYNDROME 9; BBS9

BBS9 is an autosomal recessive disorder characterized by obesity, polydactyly, renal anomalies, retinopathy, and mental retardation (Abu-Safieh et al., 2012).For a general phenotypic description and a discussion of genetic heterogeneity of Bardet-Biedl syndrome, see BBS1 (OMIM ).

• Intellectual disability
• Obesity
• Rod-cone dystrophy
• Polydactyly
• Abnormality of the kidney

SOURCES: OMIM MENDELIAN

Low match BARDET-BIEDL SYNDROME 7; BBS7

BBS7 is an autosomal recessive disorder characterized by retinitis pigmentosa, postaxial polydactyly, mental retardation, obesity, renal anomalies, and hypogenitalism (Harville et al., 2010). Zaghloul and Katsanis (2009) estimated the contribution of BBS7 gene mutations to the total BBS mutational load to be 1.50%.For a general phenotypic description and a discussion of genetic heterogeneity of Bardet-Biedl syndrome, see BBS1 (OMIM ).

• Intellectual disability
• Obesity
• Rod-cone dystrophy
• Hypogonadism
• Polydactyly

SOURCES: OMIM MENDELIAN