It is estimated that BBS affects around 1 in 250,000 people around the world and affects both males and females equally. The syndrome is more common in certain areas of the world affecting more populations of Newfoundland (1 in 17,500) and the Bedouin population of Kuwait (1 in 13,500). One of the specific gene mutations (BBS10) associated with BBS is particularly common in South Africa.

BBS can be caused by mutations in more than 20 different genes, and it is typically inherited as an autosomal recessive condition. Many of the gene mutations that are known to cause BBS include: BBS1, BBS2, ARL6 (BBS3), BBS4, BBS5, MKKS (BBS6), BBS7, TTC8 (BBS8), BBS9, BBS10, TRIM32 (BBS11), BBS12,MKS1 (BBS13), CEP290 (BBS14), WDPCP (BBS15),SDCCAG8 (BBS16), LZTFL1 (BBS17), BBIP1 (BBS18), IFT27 (BBS19), IFT72 (BBS20), and C8ORF37(BBS21).In spite of the many gene mutations identified above, there are still around 20-30 % of individuals affected by BBS, who have unidentified gene mutations. Certain trends have emerged indicating associations between patients with certain mutations and the specific symptoms of BBS. For example, patients with mutations in the BBS2, BBS3, and BBS4 genes experience classic deterioration of vision, while patients with a BBS10 gene mutation are typically much more prone to obesity and diabetes.Most genes linked to BBS encode proteins that form cilia and basal bodies. Cilia are the tiny hair-like structures that cover different types of cells in the body, and the basal bodies work to anchor the cilia to the cells. Cilia can be motile or immotile. While motile (or moving) cilia work to beat motion, such as keeping nasal airways clear of dirt by moving protective mucus through, domitle (primary) cilia are important signaling hubs passing information from one cell to another, such as determining urine flow in the kidneys. It seems that most gene mutations in BBS generally affect immotile cilia.

The signs and symptoms of BBS vary considerably among affected individuals, even within the same family. Common symptoms and signs include:

Primary characteristics include:

• Progressive vision loss, which is due to deterioration of the eye’s retina. This typically starts occurring in mid-childhood with problems around night vision and then blind spots in peripheral vision. Most individuals with BBS also develop blurred central vision leading to legal blindness by adolescence or early adulthood (over 90% of cases)

• Obesity developing around 2-3 years of age

• Polydactyly (extra fingers or toes)

• Hypogonadism (reduced hormone production by the testes and ovaries), which in turn can result in infertility 

• Kidney abnormalities

• Learning disabilities 

Secondary characteristics include:

• Delayed development

• Neurological problems leading to gait and coordination impairment

• Behavioral disorders

• High blood pressure

• Diabetes (specifically type II diabetes in estimately 45% of cases)

• Heart defects

• Speech disorders

• Dental abnormalities including small teeth, small lower jaw, short teeth

• Flat, wide feet with no arches

• Thyroid complications

• Lack of a sense of smell (anosmia)

• Strabismus or lazy eye

• Short stature (compared to parents’ height)

• Toe and finger abnormalities, such as being short; curved (especially outer fingers or toes); mildly webbed (particularly affecting the 2nd and 3rd toes)

An individual is typically diagnosed with BBS if they have four of the primary characteristics (above) or three primary and at least two secondary characteristics (above). Some affected individuals may not have all of the symptoms and signs, and may not receive a clear diagnosis for many years. Healthcare professionals will typically investigate an individuals’ medical history, symptoms, conduct a physical exam and review laboratory test results before making a BBS diagnosis.

Genetic testing can be used to confirm a BBS diagnosis in some individuals with certain gene mutations like BBS1 and BBS10.

As there is no cure for BBS, treatment involves treating the individual’s specific symptoms and consequently the care of multiple healthcare specialists. 

• For progressive vision loss, there is no specific treatment, but early evaluation can be helpful in determining vision aids and mobility training. Young children should be informed and educated to prepare accordingly for the prospect of future blindness.

• Obesity and related complications (e.g. diabetes, high blood pressure) can be managed through a combination of education, diet, exercise and behavioral interventions at an early age. 

• Intellectual disability and speech problems may be managed through early intervention, including special education and speech therapy where needed.

• Individuals with BBS may require surgery for polydactyly or genital abnormalities. Kidney transplants may also be needed, but the subsequent immunosuppressants after a transplant may increase obesity complications. 

• In managing hypogonadism, children with BBS approaching puberty should have their hormone levels assessed to determine whether hormone replacement therapy is needed. Adolescents and young adults with BBS should also be advised on contraception, as not all individuals affected by BBS are infertile. 

As BBS symptoms are highly variable across individuals, it can be challenging to predict the course of the disease. More severe symptoms, such as kidney malfunction or obesity complications can lead to early death. However, most individuals with BBS that receive proper treatment and monitoring seem to have a normal or at least near-normal life expectancy. 

Bardet Biedl Syndrome Foundation. What is BBS? N.d. Available from: https://www.bardetbiedl.org/what-is-bbs#nine 

National Organization for Rare Disorders. Bardet-Biedl  Syndrome. 2017. Available from: https://rarediseases.org/rare-diseases/bardet-biedl-syndrome/

National Center for Advancing Translational Sciences: Genetic and Rare Diseases Information Center. Bardet-Biedl Syndrome. 2020. Available from: https://rarediseases.info.nih.gov/diseases/6866/bardet-biedl-syndrome

Myriad Women’s Health. Bardet-Biedl Syndrome, BBS1-Related. 2020. Available from: https://myriadwomenshealth.com/diseases/bardet-biedl-syndrome-bbs1-related/