Bardet-Biedl Syndrome 17

A number sign (#) is used with this entry because Bardet-Biedl syndrome-17 (BBS17) is caused by homozygous or compound heterozygous mutation in the LZTFL1 gene (606568) on chromosome 3p21.

Description

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 (209900).

Clinical Features

Deffert et al. (2007) studied 2 sibs with Bardet-Biedl syndrome (BBS) from a consanguineous Algerian family. Both sibs presented with developmental delay, obesity, unilateral central polydactyly, bilateral postaxial polydactyly of feet, situs inversus, and hypogenitalism with micropenis and atrophic testes. The younger sib was 9 years old at the time of the report; the older sib had died at the age of 22 of renal failure, with which he had been diagnosed at age 17 years. Polydactyly of the right hand was insertional, with a Y-shaped third metacarpal.

Marion et al. (2012) followed up on the surviving Algerian sib reported by Deffert et al. (2007). At 10 years of age the patient presented with retinal degeneration with an extinguished electroretinogram, obesity (+4 SD), cognitive impairment, polydactyly, hypogonadism, polyuria and polydipsia with mild biologic kidney alterations, and complete visceral situs inversus.

Schaefer et al. (2014) described dizygotic twin sisters with BBS who were 36 years old at the time of the report. Both presented with polydactyly consisting of 6 toes on each foot and 7 fingers on each hand. Polydactyly was mesoaxial, with hypoplasia and fusion between the third and fourth metacarpal bones. Extra digits were removed at 3 months of age. Both had retinitis pigmentosa, cognitive impairment, and renal dysfunction. Kidney transplantation was performed in 1 sister at 23 years of age. Anosmia was present in 1 sib and hyposmia in the other; the anosmic sib had abnormal enlarged cilia, but abundant mobile cilia with normal morphology were present in the nose of the hyposmic sib. Schaefer et al. (2014) suggested that mesoaxial polydactyly of the hands may indicate a genotype-phenotype correlation which could guide screening for LZTFL1 mutation.

Molecular Genetics

Deffert et al. (2007) did not identify a causative mutation in the BBS1 (209901) through BBS10 (610148) genes in the surviving sib with Bardet-Biedl syndrome from a consanguineous Algerian family. In this patient, Marion et al. (2012) detected homozygosity for a 5-bp deletion in the LZTFL1 gene (606568.0001). Both parents and unaffected sibs were heterozygous for the mutation. DNA was not available from the deceased sib.

Schaefer et al. (2014) identified compound heterozygosity for mutations in the LZTFL1 gene (606568.0002-606568.0003) in dizygotic twin sisters with Bardet-Biedl syndrome.