Bardet-Biedl syndrome

Other Names: BBS; Biedl-Bardet Syndrome

Bardet-Biedl syndrome is a disorder that affects many parts of the body. The signs and symptoms of this condition vary among affected individuals, even among members of the same family. Vision loss is one of the major features of Bardet-Biedl syndrome.

Epidemiology

In most of North America and Europe, Bardet-Biedl syndrome has a prevalence of 1 in 140,000 to 1 in 160,000 newborns. The condition is more common on the island of Newfoundland (off the east coast of Canada), where it affects an estimated 1 in 17,000 newborns. It also occurs more frequently in the Bedouin population of Kuwait, affecting about 1 in 13,500 newborns.

Cause

Bardet-Biedl syndrome can result from mutations in at least 14 different genes (often called BBS genes). These genes are known or suspected to play critical roles in cell structures called cilia. Cilia are microscopic, finger-like projections that stick out from the surface of many types of cells. They are involved in cell movement and many different chemical signaling pathways. Cilia are also necessary for the perception of sensory input (such as sight, hearing, and smell). The proteins produced from BBS genes are involved in the maintenance and function of cilia.

Mutations in BBS genes lead to problems with the structure and function of cilia. Defects in these cell structures probably disrupt important chemical signaling pathways during development and lead to abnormalities of sensory perception. Researchers believe that defective cilia are responsible for most of the features of Bardet-Biedl syndrome.

About one-quarter of all cases of Bardet-Biedl syndrome result from mutations in the BBS1 gene. Another 20 percent of cases are caused by mutations in the BBS10 gene. The other BBS genes each account for only a small percentage of all cases of this condition. In about 25 percent of people with Bardet-Biedl syndrome, the cause of the disorder is unknown.

In affected individuals who have mutations in one of the BBS genes, mutations in additional genes may be involved in causing or modifying the course of the disorder. Studies suggest that these modifying genes may be known BBS genes or other genes. The additional genetic changes could help explain the variability in the signs and symptoms of Bardet-Biedl syndrome. However, this phenomenon appears to be uncommon, and it has not been found consistently in scientific studies.

Inheritance

Autosomal recessive inheritance, a 25% chance

Bardet-Biedl syndrome is typically inherited in an autosomal recessive pattern, which means both copies of a BBS gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Signs and symptoms

Bardet-Biedl syndrome (BBS) affects many parts of the body. The major features include:

• Progressive vision loss due to deterioration of the retina. This usually begins in mid-childhood with problems with night vision, followed by the development of blind spots in peripheral vision. Blind spots become bigger with time and eventually merge to produce tunnel vision. Most individuals also develop blurred central vision and become legally blind by adolescence or early adulthood (over 90% of cases).
• Extra finger next to the pinky (postaxial polydactyly)
• Kidney problems (polycystic kidneys)
• Obesity that develops around 2-3 years of age
• Abnormalities of the genitalia and infertility due to hypogonadism
• Learning disorders

BBS may also be associated with other features, including:

• Diabetes
• High blood pressure
• Heart defects
• Bowel disease (Hirschsprung disease)
• Neurological problems resulting in gait and coordination impairment
• Speech and language problems
• Behavioral disorders
• Distinctive facial appearance
• Dental abnormalities

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. 80%-99% of people have these symptoms

• Abnormal electroretinogram
• Intellectual disability(Mental deficiency)
• Multicystic kidney dysplasia
• Obesity(Having too much body fat)
• Pigmentary retinopathy
• Postaxial hand polydactyly(Extra little finger)

30%-79% of people have these symptoms

• Hypertension
• Hypogonadism(Decreased activity of gonads)
• Hypoplasia of penis(Underdeveloped penis)
• Hypoplasia of the ovary(Underdeveloped ovary)
• Nystagmus(Involuntary, rapid, rhythmic eye movements)
• Short stature(Decreased body height)

5%-29% of people have these symptoms

• Cryptorchidism(Undescended testes)
• Downslanted palpebral fissures(Downward slanting of the opening between the eyelids)
• Finger syndactyly
• Generalized hirsutism(Excessive hairiness over body)
• Hearing impairment(Deafness)
• Hepatic fibrosis
• Low-set, posteriorly rotated ears
• Medial flaring of the eyebrow
• Nephrotic syndrome
• Neurological speech impairment(Speech disorder)
• Prominent nasal bridge(Elevated nasal bridge)
• Short neck(Decreased length of neck)
• Skeletal muscle atrophy(Muscle degeneration)

Diagnosis

BBS must be suspected in a fetus/infant with structural kidney disease, genitourinary malformations, and/or polydactyly as these may be the only features of BBS evident in this cohort.

Centralobesity, which often develops in the first year of life, is another prominent early feature of BBS that should raise suspicion of this diagnosis.

Manifestations of cone-rod dystrophy (photophobia, decreased visual acuity, and loss of color discrimination) and chronic kidney disease (polyuria and polydipsia) may not be present until children are school-aged, while manifestations of hypogonadism (lack of pubertal development) are evident even later, in early adolescence. Because BBS is genetically heterogeneous with significant clinical overlap with other ciliopathies, recommended molecular genetic testing approaches include either gene-targeted testing (multigene panel) or comprehensive genomic testing (exome sequencing).

Treatment

There is no cure for Bardet-Biedl syndrome. Treatment generally focuses on the specific signs and symptoms in each individual:

• While there is no therapy for the progressive vision loss, early evaluation by a specialist can help to provide vision aids and mobility training. Additionally, education of affected children should include planning for future blindness.
• Management of obesity may include education, diet, exercise, and behavioral therapies beginning at an early age. Complications of obesity such as abnormally high cholesterol and diabetes mellitus are usually treated as they are in the general population.
• Management of intellectual disability includes early intervention, special education and speech therapy as needed. Many affected adults are able to develop independent living skills.
• Although kidney transplants have been successful, the immunosuppressants used after a transplant may contribute to obesity. Affected individuals may also need surgery for polydactyly (extra fingers and/or toes) or genital abnormalities.
• As children approach puberty, hormone levels should be monitored to determine if hormone replacement therapy is necessary. Additionally, it should not be assumed that affected individuals are infertile - so contraception advice should be offered.

NIH genetic and rare disease info

• NIH info on Bardet-Biedl syndrome

Bardet-Biedl syndrome is a rare disease.

Bardet-Biedl syndrome Resources
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