Bardet-Biedl syndrome, BBS12-related

What is Bardet-Biedl Syndrome, BBS12-related?

Bardet-Biedl syndrome (BBS), caused by harmful genetic changes (mutations) in the BBS12 gene, is an inherited disease that causes vision problems; mild obesity; extra fingers or toes (polydactyly); genital and kidney problems; and learning difficulties.

A hallmark of BBS is vision loss caused by degeneration of the retina (rod-cone dystrophy). It begins as night blindness in childhood and progresses to a loss of peripheral vision. Individuals with BBS can also lose central vision during childhood or adolescence. The mean age at which individuals become legally blind is 15.5 years. By early adulthood, affected individuals are severely visually impaired.

Kidney problems are present in most individuals with BBS and can range from few functional problems to life-threatening kidney failure. Many affected individuals have developmental disabilities. This can range from mild learning disabilities or delayed emotional development to more severe symptoms. In some individuals these delays are due in part to vision loss, while in other cases they are a direct result of the disease.

Rarer features include liver disease; diabetes; neurological issues such as poor balance and coordination; behavioral issues; characteristic physical features (facial features and dental irregularities); high blood pressure; defects of the heart or reproductive system; and hearing loss, among others. These features may vary according to the type of the disease. Some secondary features reported in BBS, BBS12-related are diabetes, dental irregularities, heart disease, and behavioral issues.

There are at least 19 genes associated with BBS, and some of these genes have been associated with other syndromes (e.g., Laurence-Moon syndrome, retinitis pigmentosa, and Meckel-Gruber syndrome). It is unclear whether these represent a spectrum of disease or whether BBS is distinct from the other associated syndromes. A few reports identified BBS12 mutations in individuals with retinitis pigmentosa (vision loss only).

How common is Bardet-Biedl Syndrome, BBS12-related?

Mutations in BBS12 account for approximately 11% of BBS cases. The number of individuals affected with BBS ranges from 1 in 100,000 individuals in North America to 1 in 160,000 in Europe. Disease frequency also varies by population, being higher in populations where marriage between blood relatives (consanguinity) is common or the population was isolated. Populations with higher frequencies BBS12-related cases of BBS are the Romani and Iranian populations.

How is Bardet-Biedl Syndrome, BBS12-related treated?

There is no cure for BBS, and a team of specialists must manage the associated symptoms. A geneticist is typically involved in the diagnosis and centralized management of an affected child. Management may include monitoring; provision of aids and therapies; or surgery. Patients are recommended to undergo regular monitoring of vision; weight; blood pressure; thyroid, kidney, and liver function; and development. An ophthalmologist will manage vision issues, and there may be aids that help improve quality of life. A registered dietician may help with managing weight, and medications may help with high blood pressure. An endocrinologist may be consulted for diabetes, thyroid disease, and proper pubertal development. Kidney issues are managed in a standard fashion, but if they become life-threatening, dialysis or transplantation may be necessary. Surgery can correct some birth defects (extra digits may be removed in childhood, or heart and vaginal malformation may be corrected), and an orthodontist may assist with correction of dental anomalies. Early intervention and therapies may assist with learning difficulties, and a pediatric neurologist may help monitor the progression of development, if necessary.

What is the prognosis for an individual with Bardet-Biedl Syndrome, BBS12-related?

Predicting symptoms and the course of the disease for individuals with BBS can be difficult due to the variable nature of the condition, even within families. One of the most consistent features is progressive vision loss, which frequently leads to blindness. Kidney disease is also frequent and is a major cause of early death for individuals with BBS, though complications of obesity, heart disease, and diabetes have also been reported as causes of death. However, a majority of individuals may have a normal or near-normal life expectancy, though with various impairments.