Bardet-Biedl Syndrome 21

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Retrieved

2019-09-22

Source

Omim

Trials

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Genes

MKS1, BBS10, SDCCAG8, LZTFL1, BBIP1, CEP290, ARL6, IFT27, BBS2, MKKS, BBS4, BBS1, TTC8, ALMS1, IFT172, C8orf37, NPHP1, TMEM67, TBC1D32, BBS7, TRIM32, BBS9, BBS5, BBS12, TRAPPC3, ASTN2, PIGX, CEP19, ZDHHC24, CCDC28B, LEP, GLIS2, RTEL1, PLLP, PYY3, SULT1A4, PEG13, AZIN1, STOML3, RIN2, MAGEL2, CBLL2, MARVELD2, MYO3B, INPP5E, USP35, MUL1, WDPCP, IFT74, CEP131, SCAPER, INVS, NPY2R, NPY, NMB, NDN, MYO9A, MYO7A, RAB8A, KIFC3, KIF2A, INSR, IL18, GPT, GFAP, ERG, CCT, TNFRSF11B, PRKN, PCM1, ADIPOQ, CEP164, STUB1, FEM1B, RAPGEF5, IQCB1, FEZ1, TRPV1, PDE6B, VEGFA, SULT1A3, RHO, RFX1, RCVRN, PECAM1, SLX1A-SULT1A3

Drugs

Adeno-associated virus serotype 8 containing the human RdCVF sequence and the human RdCVFL sequence, Combination of three adeno-associated viral vectors of serotype 8 containing the 5'-, the body- and the 3'- coding sequences of human CEP290 fused to inteins, Leuprolide acetate ( LUPRON INJECTION )

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A number sign (#) is used with this entry because of evidence that Bardet-Biedl syndrome-21 (BBS21) is caused by homozygous mutation in the C8ORF37 gene (614477) on chromosome 8q22.

Mutation in the C8ORF37 gene can also cause cone-rod dystrophy (CORD16; 614500) and isolated retinitis pigmentosa (RP64; 614500).

Description

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 (209900).

Clinical Features

Heon et al. (2016) studied a 17-year-old Caucasian girl, born to consanguineous parents, who exhibited features that met the diagnostic criteria for Bardet-Biedl syndrome (BBS), including slowly progressive rod-cone dystrophy, 3-limb postaxial polydactyly, near-obesity (BMI, 29.1), mild learning difficulty, abnormally positioned uterus, and horseshoe kidney. Other features included high myopia and elevated liver enzymes; however, liver ultrasound was normal, as were hearing, behavior, and brain MRI. Funduscopy showed retinal atrophy around the optic nerve and inferiorly, consistent with myopic degenerative changes; however, mild vessel attenuation and a flat-appearing retina were also observed, suggestive of retinitis pigmentosa. Fundus autofluorescence (AF) showed increased AF in a paramacular ring and at the fovea, whereas a speckled pattern of AF was seen in the inferior retina, consistent with diffuse retinal pigment epithelium dysfunction. Full-field electroretinography (ERG) recordings suggested a progressive rod-cone dystrophy, with nondetectable dim light scotopic responses (rods) and severely attenuated cone ERGs bilaterally.

Khan et al. (2016) reported a 6-year-old obese Saudi Arabian boy with reduced and progressively worsening vision from 2 years of age. Funduscopy revealed chorioretinal atrophy consistent with myopia, and ERG showed minimal photopic response and moderately delayed or depressed scotopic response. Optical coherence tomography showed macular retinal thinning, particularly of the outer retina. The patient also had speech delay, although he was in an age-appropriate grade at school, and exhibited postaxial polydactyly of all 4 extremities as well as dental anomalies, including hypodontia. Based on the presence of 3 primary features of BBS (retinal dystrophy, polydactyly, and obesity) and 2 secondary features (speech delay and abnormal dentition), the patient was diagnosed with Bardet-Biedl syndrome. Khan et al. (2016) noted that this patient exhibited cone-rod dystrophy, rather than the rod-cone dystrophy more commonly associated with BBS.

Molecular Genetics

In a 17-year-old girl with BBS, who was negative for mutation in known BBS-associated genes, Heon et al. (2016) performed whole-genome sequencing and identified homozygosity for a nonsense mutation in the C8ORF37 gene (K102X; 614477.0007) that segregated fully with disease in the family. Direct sequencing of C8ORF37 in 53 additional unrelated BBS patients did not detect any more disease-causing mutations. Noting that some patients with apparently nonsyndromic C8ORF37-associated retinal disease (see 614500) also exhibited polydactyly, Heon et al. (2016) questioned whether that finding was truly isolated, since signs of BBS may be mild and overlooked if not functionally significant.

In a 6-year-old Saudi Arabian boy with BBS, who was negative for 2 known hotspot mutations in the BBS1 (209901) and BBS10 (610148) genes, Khan et al. (2016) performed targeted next-generation sequencing of BBS-associated genes but did not find any putatively pathogenic mutations. However, extended analysis of additional ciliopathy genes revealed that the patient was homozygous for a missense mutation in the C8ORF37 gene (R177W; 614477.0003), for which his unaffected parents were heterozygous. Khan et al. (2016) noted that the R177W variant previously had been reported in patients with isolated cone-rod dystrophy (CORD16; 614500).