Bardet-Biedl syndrome (BBS) is a rare, autosomal-recessive ciliopathy characterized by retinal dystrophy, obesity, renal abnormalities, and genital abnormalities, postaxial polydactyly and learning difficulties. To date, mutations in more than 20 different genes have been described as being responsible for BBS (ARL6, BBIP1, BBS1, BBS10, BBS12, BBS2, BBS4, BBS5, BBS7, BBS9, CCDC28B, CEP290, IFT27, LZTFL1, MKKS, MKS1, SDCCAG8, TMEM67, TRIM32, TTC8, WDPCP) 1, 11.
Autosomal recessive, digenic recessive inheritance
1/100,000-160,000 (Northern European and North American populations); 1/13,500 (Arab populations) 1, 2, 11.
Primary clinical features for Bardet-Biedl syndrome include the following:
- Rod-cone dystrophy, (>90% of cases)1
- Postaxial polydactyly (21% of cases)1
- Truncal obesity(72-92% of cases)1
- Learning disabilities and cognitive impairment.
- Hypogonadism (males) or genital abnormalities (in females)2
- Renal anomalies (53-82% of cases) 3, 1, 11.
Secondary clinical features of Bardet-Biedl syndrome include the following1, 11:
- Speech delay/disorder
- Developmental delay
- Behavioral abnormalities
- Eye abnormalities (strabismus, cataracts, and astigmatism)
- Ataxia/poor coordination/imbalance and mild hypertonia
- Diabetes mellitus
- Orodental abnormalities (dental crowding, hypodontia, small dental roots, and high-arched palate)
- Cardiovascular anomalies5.
- Hepatic involvement
- Hirschsprung disease
- The diagnosis of Bardet-Biedl syndrome relies on clinical findings and family history.
- Suggested criteria is the presence of:
o 4 primary features or
o 3 primary features + 2 secondary features
- Diagnosis is confirmed by the identification of a pathogenic variant in one of the following genes: ARL6, BBIP1, BBS1, BBS10, BBS12, BBS2, BBS4, BBS5, BBS7, BBS9, CCDC28B, CEP290, IFT27, LZTFL1, MKKS, MKS1, SDCCAG8, TMEM67, TRIM32, TTC8, WDPCP.
There is no cure for Bardet-Biedl syndrome to date, but treatment can relieve symptoms 11.
- Visual aids and educational programs for the visually impaired.
- Obesity is managed with diet, exercise, and behavioral therapies.
- Speech therapy for speech delay/impairment.
- Renal anomalies and hypertension are treated as in the general population.
- Hydrocolpos, vaginal atresia, or hypospadias may be surgically corrected.
- Hormone replacement therapy for hypogonadism.
- Cardiac abnormalities are treated as in the general population.
- McKusick-Kaufman syndrome
- Alström syndrome
- Joubert syndrome
- Senior-Løken syndrome (SLS)
- Leber congenital amaurosis (LCA)
- Biemond syndrome II
- Chronic pancreatitis
To confirm/establish the diagnosis, CENTOGENE offers the following testing strategy for Bardet-Biedl syndrome using NGS Panel Genomic:
Step 1: Whole genome sequencing from a single filter card (drop of blood), covering the entire genic region (coding region, exon/intron boundaries, intronic and promoter) for all the genes included in the Bardet-Biedl syndrome panel. Copy Number Variants analysis derived from NGS data is also included.
Step 2: If no pathogenic variant is identified in Step1, continue with bioinformatics analysis covering genes that are either implicated or associated with overlapping phenotype or similar pathways.
- Individuals with a positive family history of Bardet-Biedl syndrome.
- Individuals with most common symptoms of Bardet-Biedl syndrome (regardless of family history).
Confirmation of a clinical diagnosis through genetic testing of Bardet-Biedl syndrome can allow for genetic counseling and may direct medical management.