Bardet-Biedl syndrome (BBS) is characterized by rod-cone dystrophy (>90%), truncal obesity (72%), postaxial polydactyly, cognitive impairment, male hypogonadotrophic hypogonadism, complex female genitourinary malformations, and renal abnormalities. The visual prognosis for children with BBS is poor. Night blindness is usually evident by age seven to eight years; the mean age of legal blindness is 15.5 years. Birth weight is usually normal, but significant weight gain begins within the first year and becomes a lifelong issue for most individuals. A majority of individuals have significant learning difficulties, but only a minority have severe impairment on IQ testing. Renal disease is a major cause of morbidity and mortality.
The diagnosis of BBS is established by clinical findings. Fourteen genes are known to be associated with BBS: BBS1, BBS2, ARL6 (BBS3), BBS4, BBS5, MKKS (BBS6), BBS7, TTC8 (BBS8), BBS9, BBS10, TRIM32 (BBS11), BBS12, MKS1 (BBS13), and CEP290 (BBS14). Mutations in WDPCP and SDCCAG8 may be associated with BBS15 and BBS16, respectively. Molecular genetic testing is available on a clinical basis for all 14 known BBS-related genes and for WDPCP, mutations in which may be associated with BBS.
BBS is typically inherited in an autosomal recessive manner. Both interfamilial and intrafamilial phenotypic variability exists. In some families, mutations in more than one BBS locus may result in a clinical phenotype of BBS. However, such families are difficult to identify and by previous estimations may account for less than 10% of all BBS. It is thus prudent to use the following autosomal recessive risk figures when providing genetic counseling: at conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing is possible if the disease-causing mutations in a family are known. Prenatal diagnosis using second-trimester ultrasound examination to detect anomalies associated with BBS such as postaxial polydactyly and renal cysts has been reported. Few laboratories offering molecular genetic testing for prenatal diagnosis of BBS are listed in the GeneTestsTM Laboratory Directory; however, for pregnancies at increased risk in families in which the disease-causing mutations have been identified, prenatal testing may be available through laboratories offering custom prenatal testing.