What are the other Names for this Condition? (Also known as/Synonyms)

• BBS (Bardet-Biedl Syndrome)
• Laurence-Moon-Bardet-Biedl Syndrome (LMBBS)
• LMS (Laurence-Moon Syndrome)

What is Bardet-Biedl Syndrome? (Definition/Background Information)

• Bardet-Biedl Syndrome (BBS) is an uncommon genetic disorder that affects multiple parts of the human body. Inhabitants of Canadian Newfoundland and those belonging to the Bedouin community of Kuwait seem to have a higher risk for developing the disorder
• Bardet-Biedl Syndrome can manifest during infancy, with symptoms developing or progressing as the child grows older. Since BBS has a genetic cause, the single major risk factor for developing this condition is having a family history of the same
• The majority of individuals with Bardet-Biedl Syndrome inherit the disorder in an autosomal recessive manner. The condition is caused by mutations in at least 12 genes (known as the BBS genes)
• BBS genes code for proteins of cellular structures called cilia, which are the projections on a cell surface involved in transmitting signals as well as cellular movement and migration. Mutations in the BBS genes give rise to abnormal cilia. As a result, multiple structures and functions of the body are affected
• Bardet-Biedl Syndrome is characterized by a spectrum of signs and symptoms. Since many parts of the body may be involved, the type and severity of symptoms may differ in each affected individual. Vision defects are the most common symptoms, along with polydactyly (extra finger or toe), abnormal body fat distribution, small genitals in males, and learning disabilities
• As a consequence of the syndrome being multi-systemic, many complications are known to arise including blindness, high blood pressure, type-2 diabetes, kidney malfunction, and infertility
• A diagnosis of Bardet-Biedl Syndrome may be made through a number of tests, including a physical examination, evaluation of family medical history, assessment of symptoms, and genetic testing
• Treatment options for Bardet-Biedl Syndrome are generally tailored towards addressing the symptoms. Individuals with significant symptoms related to the eye, kidney, ear, and the gastrointestinal system may be referred to appropriate healthcare professionals
• The prognosis for Bardet-Biedl Syndrome is typically guarded, particularly if renal failure occurs as a complication. But, it also depends upon the severity of the signs and symptoms

Who gets Bardet-Biedl Syndrome? (Age and Sex Distribution)

• Bardet-Biedl Syndrome is a relatively rare genetic disorder that is manifested at birth
• About 1 in 150,000 individuals are reported to be affected; a majority of them belonging to the North American and European populations
• Inhabitants of Newfoundland (off the coast of Canada) and those belonging to the Bedouin population of Kuwait, show an increased susceptibility to the condition. In these populations, 1 in every 13,500-17,000 newborns are reported to be affected, implying that the disorder is 10 times more common among them
• The disorder can occur in both genders, although males are more vulnerable with a slightly increased rate of occurrence at 1.3:1 (male-female), when compared to females

What are the Risk Factors for Bardet-Biedl Syndrome? (Predisposing Factors)

• Bardet-Biedl Syndrome is a genetic disorder, and hence, having a family history of the condition is the single major risk factor for its development

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one's chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Bardet-Biedl Syndrome? (Etiology)

Bardet-Biedl Syndrome is generally inherited as an autosomal recessive disorder. At least 12 different genes, collectively termed as the BBS genes, are involved in the development of this disorder, in a majority of cases.

• Mutations in BBS genes are believed to contribute to abnormalities in the structure and function of cilia, which are tiny projections on the cell surfaces. Many different types of cells may be affected
• The cilia are involved in signal transmission, reception of sensory input (such as vision, sense of smell, hearing), and cellular movement. Therefore, any abnormality in these projections can potentially affect many different signaling pathways and variations in functions. For example, dysfunction of cilia may lead to deterioration of rod and cone cells in the eye, which receive light stimuli for vision
• Of the 12 BBS genes known to be involved in Bardet-Biedl Syndrome, BBS1 gene mutations are reported to contribute to about 25% of the cases and BBS10 gene mutations account for another 20%. Mutations in the BBS genes other than BBS1 and BBS10 genes are known to contribute to only a small percentage of Bardet-Biedl Syndrome cases
• Some studies have reported that mutations in additional BBS genes or some other genes might contribute to changes in the type or severity of symptoms. This could explain the wide spectrum of symptoms characterizing this disorder; however, such studies have not shown consistent results
• In approximately 25% of the affected population, the cause is unknown. The scientists believe that mutations in genes other than the identified BBS genes may be involved

Autosomal recessive: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children, born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

What are the Signs and Symptoms of Bardet-Biedl Syndrome?

The signs and symptoms of Bardet-Biedl Syndrome may begin to manifest during infancy, with some progressing or developing as the child grows older. The following are some commonly reported symptoms of Bardet-Biedl Syndrome:

• Vision-related (retinal dystrophy)
  • Night vision problems in children
  • Peripheral vision affected by blind spots
  • Tunnel vision, owing to the blind spots in peripheral vision growing and merging
  • Loss of vision, legal blindness
• Obesity
  • Weight gain starting in early childhood and continuing throughout one’s life
  • Abnormal fat distribution in the body, with more fat in chest and abdomen than arms and legs (truncal obesity)
• Polydactyly or extra finger and/or toe
• Congenital heart defects
• Abnormalities in genitals
  • Small genital size (especially in males)
  • Reduced synthesis of sex hormones
  • Infertility
• Learning disabilities; impaired speech and hearing
• The sense of smell is affected; a complete lack of smell sense (anosmia) is reported in some cases
• Compromised motor skills:
  • Lack of or impaired coordination
  • Problems in voluntary movement
  • Gait problems and clumsiness
• Behavioral issues including outbursts, emotional immaturity, etc.
• Dental abnormalities
• Impaired kidney function
• Organs in the gastrointestinal (GI) tract may be affected

Note: The symptoms and severity of Bardet-Biedl syndrome are reported to vary greatly, even among affected members from within the same family.

How is Bardet-Biedl Syndrome Diagnosed?

Bardet-Biedl Syndrome may be diagnosed using the following tools:

• A thorough physical examination
• An evaluation of family medical history
• An assessment of symptoms
• If an individual has vision defects, possible referral to a specialist for tests such as the following:
  • Eye examination
  • Electroretinogram (ERG), wherein the response of retina to light stimulation is measured 
• Examination of various body systems that may be affected including dental, neurological, heart, digestive, reproductive system, etc.
• Genetic testing to detect mutations in BBS genes, where testing is available
• Prenatal second-trimester ultrasound scanning in pregnancies with increased risk can help look for polydactyly and renal anomalies (enlarged hyperechoic kidneys), which can help suspect BBS

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Bardet-Biedl Syndrome?

Some of the potential complications of Bardet-Biedl Syndrome may include:

• Blurred central vision and legal blindness (by adolescence or early adulthood)
• Type-2 diabetes
• High blood pressure, heart defects
• Increased cholesterol levels in the body (hypercholesterolemia)
• Decreased sex hormone synthesis and infertility in males
• Kidney failure
• Malfunction of the liver and organs of the GI tract

How is Bardet-Biedl Syndrome Treated?

The treatment of Bardet-Biedl syndrome is tailored to the type of symptoms an affected individual develops.  If an individual has multiple symptoms, a coordinated care may be required from professionals in many medical specialties, including paediatricians, heart specialists, dental professionals, and nephrologists (those who specialize in kidney disease).

• For retinal dystrophy, currently no effective treatment is available. A vision specialist may help manage refractive errors with vision aids
• Surgery may be recommended for extra digits in hand and foot, especially to fit footwear
• If a child is born with congenital heart or genitourinary abnormalities, corrective surgery may be an option
• Hormone replacement therapy for males with developmental issues in sex organs
• Suitable medical intervention for kidney disease with periodic monitoring of kidney function
• Diet management regimens and regular physical activity in individuals with obesity
• Periodic monitoring of glycemic index in those affected with type-2 diabetes
• Special education and therapy for the affected children

How can Bardet-Biedl Syndrome be Prevented?

• Currently, there are no specific methods or guidelines to prevent Bardet-Biedl Syndrome, since it is a genetic condition
• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders such as Bardet-Biedl Syndrome
• Regular medical screening at periodic intervals with tests and physical examinations are strongly recommended

What is the Prognosis of Bardet-Biedl Syndrome? (Outcomes/Resolutions)

• The prognosis of Bardet-Biedl Syndrome is generally guarded. However, it also depends on the severity of the signs and symptoms
• The outcome is reported to be unfavourable, especially if complications with kidney function develop

Additional and Relevant Useful Information for Bardet-Biedl Syndrome:

Bardet-Biedl Syndrome showed significant overlap with a disorder called Laurence-Moon Syndrome (LMS). In the past, these disorders were considered the same and referred to as Laurence-Bardet-Biedl Syndrome. Eventually, researchers decided that the 2 disorders despite numerous similarities were distinct entities.

However, recent research has demonstrated that some individuals with the clinical findings of Laurence-Moon Syndrome have mutations in genes linked to Bardet-Biedl Syndrome. This discovery has led some researchers to suggest that little evidence exists to continue to classify these disorders as two distinct and separate entities.