Bardet-Biedl Syndrome (BBS): A Rare Disease

Bardet-Biedl Syndrome (BBS) is a complex genetic disorder that many people don’t know about, even though it deeply affects those who have it. This rare disease affects about 1 in 250,000 people worldwide and causes a range of symptoms that make things tough for both patients and doctors. These symptoms include vision loss, obesity, kidney problems, and other issues that involve many body systems. BBS shows how complex genetic disorders can be and highlights the need for care from many different types of doctors. In this article, we will explore the genetic causes of BBS, how its symptoms can vary, and the latest progress in treating and managing the disease. By bringing attention to this rare condition, we aim to improve awareness and understanding, helping to create better outcomes for those living with Bardet-Biedl Syndrome.

What is Bardet-Biedl Syndrome (BBS)?

Bardet-Biedl Syndrome is a rare genetic disorder with many different symptoms. These symptoms can include vision loss, obesity, poor kidney function, and extra fingers or toes. More than 20 genes can lead to this syndrome, but the main problem in all cases is that the primary cilia do not work properly. Primary cilia are important for how cells communicate. Because of this, doctors classify BBS as a ciliopathy, which means it is a disease that affects the cilia.

Bardet Biedl Syndrome Diagnostics

Bardet-Biedl Syndrome (BBS) often presents with a range of symptoms affecting multiple systems, including early night blindness that progresses to blindness by the second or third decade. The most common and defining symptom is retinal degeneration, similar to retinitis pigmentosa. Patients frequently show early obesity, extra fingers or toes, and intellectual impairments.

Diagnosis typically involves identifying a combination of primary and secondary symptoms, with electroretinography (ERG) helping detect early retinal dysfunction. Genetic testing confirms the diagnosis in about 80% of cases and is essential due to BBS’s genetic diversity. The differential diagnosis includes other causes of retinal degeneration like Alström syndrome and Usher syndrome, especially important in young children where symptoms may be less distinct.

Bardet Biedl Syndrome Causes

Bardet-Biedl syndrome can come from mutations in at least 14 different genes, known as BBS genes. These genes are important for the function of cellular structures called cilia. Cilia are small, finger-like projections on many cell types that help with cell movement and various chemical signaling pathways. They are also vital for sensing things like sight, hearing, and smell. The proteins that BBS genes make are crucial for keeping cilia working well.

Mutations in BBS genes can cause problems with the structure and function of cilia. These issues likely disturb important chemical signaling pathways during development and lead to problems with sensing things. Researchers believe these faulty cilia cause most of the features of Bardet-Biedl syndrome.

About one-quarter of all Bardet-Biedl syndrome cases come from mutations in the BBS1 gene, while another 20 percent come from mutations in the BBS10 gene. The other BBS genes only cause a small number of cases. In about 25 percent of people with Bardet-Biedl syndrome, the genetic cause is unknown.

In people with mutations in one of the BBS genes, changes in other genes may also influence or change how the disorder progresses. Studies show that these other genes could be known BBS genes or completely different ones. These extra genetic changes might explain why the signs and symptoms of Bardet-Biedl syndrome vary so much. However, this is quite rare and hasn’t been consistently found in scientific research.

Bardet Biedl Syndrome Symptoms

Bardet-Biedl syndrome is a complex disorder that shows up differently in people and varies a lot within and between families. The most common symptoms include rod-cone dystrophy, which begins with night blindness in childhood and leads to progressive vision loss; extra fingers or toes on the edges of the hands or feet; obesity starting in infancy and continuing into adulthood; different levels of learning disabilities; underdeveloped male genitalia and complex issues in female reproductive organs; and kidney problems, which are a major cause of illness and death.

Several other symptoms are sometimes linked to BBS, including:

• Crossed eyes, cataracts, uneven vision, retinal changes, poor vision quality, low vision, or blindness due to damaged cells in the retina.
• Short fingers and toes and fused fingers or toes, often between the second and third toes.
• Frequent urination and excessive thirst (nephrogenic diabetes insipidus).
• Lack of coordination and balance problems.
• Slight muscle stiffness, mainly in the legs.
• Diabetes mellitus.
• Liver problems.
• Loss of smell.
• Hearing issues.
• Hirschsprung disease that can block the bowels.
• Thickening of the heart’s walls and enlarged heart chambers.
• Underdeveloped reproductive organs, kidney failure, unusual urinary openings, double uterus, divided vagina, and small uterus, ovaries, and fallopian tubes.
• Speech disorders or delays.

How Bardet Biedl Syndrome Is Inherited

Bardet-Biedl syndrome passes through families by an autosomal recessive inheritance pattern. In this pattern, both parents are carriers, having one gene linked to the syndrome and one normal gene. Each of their children has a 25 percent chance (or 1 in 4) of getting two Bardet-Biedl genes (one from each parent), which they need to get the disorder. Carriers do not show symptoms because they only have one copy of the gene. Researchers have found 18 genes that can cause BBS when they change.

How Many People Have BBS?

Bardet-Biedl Syndrome (BBS) is a “rare disease” that affects about 1 in 250,000 people worldwide. Estimates show that around 3,000 people in the United States and Canada have BBS. The syndrome is more common in certain areas, including Newfoundland in Canada and among Bedouin populations in the Middle East.

Bardet Biedl Syndrome Treatment

While there is no cure for the root cause of Bardet-Biedl Syndrome (BBS), comprehensive care from many types of doctors is crucial to manage the symptoms. Doctors intensely treat conditions like diabetes, high blood pressure, and metabolic syndrome to prevent damage to other organs such as the kidneys and eyes. Specialists handle specific problems of the disease, and kidney issues often lead to severe health problems and death in BBS patients.

In BBS, obesity and excessive eating likely come from problems in the hypothalamus part of the brain. In 2020, treatment with Setmelanotide, a drug that controls appetite and body weight, significantly reduced weight in BBS patients over a year. This medication continues to show good results in BBS patients.

Vision problems are a major concern in BBS. Early eye exams in children should look for issues like crossed eyes, involuntary eye movements, and poor vision. When needed, doctors should do tests like electroretinography and visual field testing. Patients may need to visit low-vision services. Regular check-ups with an eye doctor, at least once a year or more if needed, are important.

Experimental Medical Therapies

Currently, no clinical trials are testing treatments for vision problems in BBS. However, researchers are developing gene therapy for retinal issues in BBS using animal models. These studies involve injecting healthy BBS genes into the retina using a virus vector, leading to some improvement in light-sensing cell function. No clinical trials have tested this method in humans yet. Research continues on various genetic, stem cell, and drug treatments, along with studies that track BBS in the population to better understand the disease and look for future treatments.

Surgery

Surgery may be necessary for physical abnormalities, including those in teeth, the heart, and reproductive organs. However, currently, surgery cannot treat retinal degeneration in BBS.

Raising Awareness and Supporting Those Affected by BBS

Bardet-Biedl Syndrome (BBS) is a complex and rare genetic condition that affects individuals and families in profound ways. By understanding its symptoms, genetic causes, and the importance of early diagnosis, we can work toward better support systems and improved quality of life for those affected. Advances in medical research continue to shed light on BBS, offering hope for targeted treatments and management strategies. Raising awareness and fostering a compassionate community can help address the unique challenges of living with this rare disease, paving the way for a more inclusive and informed society.