Bardet-Biedl syndrome

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Bardet-Biedl syndrome is a disorder that affects many parts of the body. The specific features and the course of this condition can vary greatly among affected individuals.

Vision loss is one of the major features of Bardet-Biedl syndrome. Most affected individuals have a condition called cone-rod dystrophy in which the light-sensing tissue at the back of the eye (the retina) breaks down over time. Cone-rod dystrophy typically begins with problems with night vision during childhood, followed by blind spots that develop in the side (peripheral) vision. Over time, these blind spots enlarge and merge to produce tunnel vision. Most people with Bardet-Biedl syndrome also develop blurred central vision (poor visual acuity) and become legally blind by adolescence or early adulthood.

Obesity is another characteristic feature of Bardet-Biedl syndrome. Abnormal weight gain typically begins during the first months or years after birth and continues to be an issue throughout life. Complications of obesity can include type 2 diabetes, high blood pressure (hypertension), and abnormally high cholesterol levels (hypercholesterolemia).

Other common signs and symptoms of Bardet-Biedl syndrome include the presence of extra fingers or toes (polydactyly), learning problems, and intellectual disabilities. Some people have genital abnormalities, which can include an underdeveloped or abnormally developed penis, uterus, or vagina. Affected individuals may have reduced levels of sex hormones (hypogonadism) and difficulties having biological children. Many people with Bardet-Biedl syndrome also have kidney abnormalities, which can be serious or life-threatening.

Additional features of Bardet-Biedl syndrome can include impaired speech; delayed development of motor skills, such as standing and walking; and behavioral issues, such as anxiety and mood disorders. Distinctive facial features, dental abnormalities, unusually short or fused fingers or toes, and a partial or complete loss of the sense of smell (anosmia) can also occur in people with Bardet-Biedl syndrome. Additionally, this condition can affect the heart, liver, and digestive system.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Genetic changes that cause disease are called pathogenic variants. Pathogenic variants in at least 26 different genes (often called the BBS genes) cause Bardet-Biedl syndrome. These genes are known or suspected to play important roles in the function of certain types of cilia. Cilia are microscopic projections that stick out from the surface of most cells. Primary cilia are a specific type of cilia that transmit signals from the outside of the cell to the inside. They are necessary for the perception of sensory input (such as sight, hearing, and smell), and they play an important role in cell communication. The proteins produced from the BBS genes are involved in the maintenance and function of primary cilia.

Variants in BBS genes lead to problems with the structure or function of primary cilia. Changes in these cell structures likely disrupt important signaling pathways during development, including those that affect cell growth and division (proliferation) and cell specialization (differentiation). Researchers believe that most of the features of Bardet-Biedl syndrome are caused by cilia that do not function properly.

About 23 percent of all cases of Bardet-Biedl syndrome result from variants in the BBS1 gene. Another 15 percent of cases are caused by variants in the BBS10 gene. Variants in the other BBS genes account for only a small percentage of all cases of this condition. In about 20 to 30 percent of people with Bardet-Biedl syndrome, the cause of the disorder is unknown.

The presence of variants in more than one gene may explain the variability in the features and the course of Bardet-Biedl syndrome. These additional genes may be BBS genes or other genes, and variants in these genes may help modify the course of the condition. However, this phenomenon appears to be uncommon, and it has not been found consistently in scientific studies.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

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

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

In most of North America and Europe, Bardet-Biedl syndrome affects 1 in 120,000 to 160,000 newborns. The condition is more common on the island of Newfoundland (off the east coast of Canada) and in certain populations of Kuwait. Bardet-Bieldl syndrome is most common on the Faroe Islands in the North Atlantic Ocean, where it affects 1 in 3,700 newborns.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Childhood-onset truncal obesity · Very frequent (99-80%)

Truncal obesity with onset during childhood, defined as between 2 and 10 years of age.

Neurodevelopmental delay · Very frequent (99-80%)

Neurodevelopmental delay (NDD) refers to delays in the maturation of the brain and central nervous system; infants and young children with NDD may experience delays in the development of one or more skills including gross motor abilities, fine-motor coordination, language abilities and ability to solve increasingly complex problems.

Obesity · Very frequent (99-80%)

Accumulation of substantial excess body fat.

Retinal dystrophy · Obligate (100%)

Retinal dystrophy is an abnormality of the retina associated with a hereditary process. Retinal dystrophies are defined by their predominantly monogenic inheritance and they are frequently associated with loss or dysfunction of photoreceptor cells as a primary or secondary event.

Cone/cone-rod dystrophy · Very frequent (99-80%)

Abnormal electroretinogram · Frequent (79-30%)

Any abnormality of the electrical responses of various cell types in the retina as measured by electroretinography.

Abnormal oral cavity morphology · Frequent (79-30%)

Abnormality of the oral cavity, i.e., the opening or hollow part of the mouth.

Abnormality of the genitourinary system · Frequent (79-30%)

The presence of any abnormality of the genitourinary system.

Other findings in the same source

From: Orphanet

Additional reported features include Abnormality of the sense of smell (Frequent (79-30%)); Atypical behavior (Frequent (79-30%)); Autism (Frequent (79-30%)); Blindness (Frequent (79-30%)); Brachydactyly (Frequent (79-30%)); Chronic kidney disease (Frequent (79-30%)); Cognitive impairment (Frequent (79-30%)); Color vision defect (Frequent (79-30%)); Decreased HDL cholesterol concentration (Frequent (79-30%)); Dental crowding (Frequent (79-30%)). This is a selected summary, not a complete description of the condition.

Which doctor should you see?

The suggested department for discussing Bardet-Biedl syndrome is Clinical Genetics, with a clinical geneticist as the relevant type of clinician. Paediatrician (children) or physician (adults), with clinical geneticist referral.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Does the exact genetic or chromosome finding explain the observed features?
• Would a genetic counsellor help the family understand the result?
• Which organ-specific assessments are appropriate for this particular diagnosis?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Bardet-Biedl syndrome. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.