Bardet-Biedl syndrome overview
Fact-checked by Bardet-Biedl syndrome (BBS) is an inherited multisystemic disorder that can cause a wide range of symptoms, including obesity, vision problems, and learning disabilities.
BBS symptoms are highly variable and can appear at any age, making the disease difficult to diagnose. However, identifying BBS early is important so that families and their care team can develop an individualized treatment and monitoring plan to manage symptoms and prevent complications.
Globally, BBS is considered a rare disease, although its prevalence varies geographically. In North America and Europe, researchers estimate that 1 in 120,000 to 160,000 people has BBS, but in certain isolated communities with lower genetic diversity, the disease is much more common. There are fewer than 5,000 people living with BBS in the U.S.
Causes
BBS is a genetic disorder, caused by mutations that interfere with specialized cell structures called primary cilia, which help cells sense their environment and send signals. BBS gene mutations typically disrupt proteins involved in the BBSome, a complex that supports cilia function.
The primary cilia dysfunction, or ciliopathy, that results from these mutations impairs many cellular processes, leading to a wide range of possible ciliopathy symptoms.
Typically, BBS follows an autosomal recessive inheritance pattern, meaning a person needs two mutated copies of a gene — one inherited from each biological parent — to develop the disease. People with one mutated gene copy and one normal gene copy are BBS carriers and don’t usually develop symptoms. Still, there is a 25% chance that the child of two carriers with mutations in the same gene will have BBS.
Mutations in more than two dozen genes have been linked to BBS, with common ones including BBS1, BBS10, BBS2, and BBS12.
Common signs and symptoms
BBS can cause a wide range of symptoms, which vary between individuals and may evolve over time. There are six core signs of BBS that are observed in many patients:
- obesity: carrying excess weight, especially around the middle of the body (truncal obesity)
- retinal degeneration:Â vision problems related to damage to the retina, a light-sensitive area at the back of the eye
- polydactyly: extra fingers or toes at birth
- learning disabilities: challenges with learning or cognitive impairment
- renal anomalies: problems with kidney structure and function
- genital and reproductive abnormalities: low sex hormone production (hypogonadism) and/or structural or functional problems in the reproductive tract
Each person with BBS may experience different combinations of symptoms, and with varying severity. Other possible symptoms, often considered secondary disease features, include:
- metabolic problems, including diabetes or high blood pressure
- hormonal imbalances
- other eye problems, such as crossed eyes and fogging of the lens (cataracts)
- fused or short fingers or toes
- loss of smell or smell dysfunction (anosmia or hyposmia)
- delays in neurological development
- poor coordination or balance
- behavioral problems
- liver or gastrointestinal disease
- abnormal heart structure at birth
- dental problems
- abnormalities in facial structure
Some clinical signs, like polydactyly and hypogonadism, may be visible on an ultrasound before birth. Obesity and kidney problems may be evident in infancy, while learning disabilities and visual problems, often beginning with difficulty seeing in low light (night blindness), typically emerge in early childhood.
Diagnosis
A BBS diagnosis is largely clinical, relying on the recognition of characteristic signs and symptoms. Doctors may use various diagnostic and lab tests to evaluate cognition, vision, and kidney function.
Under traditional frameworks, having four primary BBS symptoms or three primary and two secondary symptoms is enough to confirm a diagnosis.
Genetic testing to identify disease-causing mutations can confirm the diagnosis in as many as about 80% of cases. Under newer recommendations, doctors may be able to make a BBS diagnosis with fewer classic symptoms when genetic test results are positive.
Early diagnosis can allow people with BBS, alongside their caregivers and health team, to monitor symptoms, manage complications, and plan ahead for changing support needs.
Treatment and management
There is no cure for BBS, so treatment aims to manage symptoms, prevent complications, and improve overall quality of life. Treatment for primary symptoms may involve strategies for dealing with:
- vision changes: using low-vision adaptations or assistive technologies
- obesity and weight management: following a personalized diet plan, safely exercising, using medication
- kidney problems: undergoing regular monitoring, controlling blood pressure, receiving standard kidney disease treatment
- reproductive problems: hormone therapy for hypogonadism or surgery if needed for structural problems
- learning accommodations: planning for support at school, participating in physical, occupational, behavioral, or speech therapy
- polydactyly: surgically removing extra fingers or toes
The only medication specifically approved for BBS is Imcivree (setmelanotide), which can be used for weight management in patients ages 2 and older.
Standard medications for diabetes, thyroid, or growth hormone deficiencies may be used if these problems arise. Surgeries for eye problems, dental issues, heart problems, or malformations in the urinary and reproductive tracts may be needed in some patients.
BBS often affects fertility, but some people with BBS can have biological children. Genetic counseling can help patients with family planning considerations.
Living with Bardet-Biedl syndrome
BBS requires multidisciplinary care throughout life, so several specialists are typically involved. Depending on a person’s symptoms, this may include:
- pediatricians
- geneticists
- kidney doctors
- eye doctors
- hormone specialists
- nerve specialists
- dentists
- heart doctors
- surgeons
- physical, occupational, and speech therapists
- dietitians
Over time, the team can begin planning for transitions from pediatric to adolescent and adult care. This planning can help ensure that patients maintain support as life circumstances change.
In addition to healthcare, patients and caregivers may need additional emotional or practical support for living with BBS. There are resources available to help with this, including:
- educational and community support from the Bardet Biedl Syndrome Foundation
- low vision resources from the Foundation Fighting Blindness
- support for genetic testing from the Uncovering Rare Obesity program
People with BBS can also join the Clinical Registry Investigating Bardet-Biedl Syndrome, which supports rare disease research by following patients worldwide and connecting them to studies.
Rare Obesity News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
