Bardet-Biedl Syndrome

Bardet-Biedl Syndrome - What is Bardet-Biedl Syndrome?

Bardet-Biedl syndrome is a condition that affects several parts of the body. It runs in families and may severely impair the sufferer.

Symptoms and features of the condition

One of the major features of Bardet-Biedl syndrome is loss of vision. Loss of vision occurs as the retina, that is the light sensing tissue or layer at the back of the eye, fails gradually.

The problems appear initially as difficulty in seeing in the dark. This is seen in childhood as a slow onset condition. This is followed by development of blind spots in vision that leads to falls and knocks initially.

Over time, these blind spots enlarge and turn into a tunnel where only the center is visible. With time the central clear area also clouds.

By the time the child reaches adolescence or early adulthood, he may become legally blind.

Another characteristic feature is obesity. There is typical abdominal obesity that begin in early childhood and continues throughout life. This may give rise to other complications like type 2 diabetes, high blood pressure and abnormally high levels of cholesterol.

Typically there may also be presence of extra fingers and/or toes along with mental retardation, learning problems, and abnormalities of the genital organs.

Bardet-Biedl syndrome epidemiology

This is a rare condition and is seen in 1 in 140,000 to 1 in 160,000 newborns in most of North America and Europe.

The prevalence is slightly higher on the island of Newfoundland (off the east coast of Canada), where it affects an estimated 1 in 17,000 newborns.

Further Bedouin population of Kuwait and Arabs are also more commonly affected with prevalence there being about 1 in 13,500 newborns.

Causes of Bardet-Biedl syndrome

Bardet-Biedl syndrome is a genetically inherited condition. It results from mutations in at least 14 different genes in the body. These are commonly called BBS genes.

It is found that these genes help make the hair like cellular structures called cilia. These cilia are involved in cell movement, different chemical signalling pathways perception of sensory input (such as sight, hearing, and smell) etc.

The BBS genes code for proteins that maintain the functions of the cilia. Defects in these genes lead to defective cilia.

The inheritance of Bardet-Biedl syndrome is autosomal recessive. This means parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene but have no symptoms of the condition (carriers of the gene).

Bardet-Biedl Syndrome Symptoms

Bardet-Biedl syndrome affects more than one system in the body and symptoms may vary between individuals even in the same family.

Common symptoms that may be seen in this condition include:-

Vision loss

One of the major features of Bardet-Biedl syndrome is loss of vision. Loss of vision occurs as the retina, that is the light sensing tissue or layer at the back of the eye, fails gradually.

The problems appear initially as difficulty in seeing in the dark. This is seen in childhood as a slow onset condition.

This is followed by development of blind spots in vision that leads to falls and knocks initially. Over time, these blind spots enlarge and turn into a tunnel where only the center is visible.

With time the central clear area also clouds. By the time the child reaches adolescence or early adulthood, he may become legally blind.

Obesity

Another characteristic feature is obesity. There is typical abdominal obesity that begins in early childhood and continues throughout life.

Obesity related conditions

Obesity may give rise to other complications like type 2 diabetes, high blood pressure and abnormally high levels of cholesterol.

Abnormalities of the fingers and/or toes

Typically there may also be presence of extra fingers and/or toes. In addition the fingers and/or toes may be short and fused together.

Learning difficulties

There may be mental retardation, learning problems, intellectual disability and impaired speech. There may be delayed development of motor skills such as standing and walking.

Behavioral problems

There are associated behavioral problems including emotional immaturity and inappropriate outbursts, and clumsiness or poor coordination.

Underdeveloped genitals

The genital organs may also be underdeveloped. The amount of sex hormones produced by males with this condition is typically low and this makes them infertile.

Kidney and other organ problems

There may be mild to severe life threatening kidney problems and kidney formation abnormalities in these patients. The heart, liver, and digestive system may also be affected. In the heart there may be enlargement of the ventricles and cardiomyopathy. In the digestive system there may be presence of fibrosis.

Facial abnormalities

There are distinctive facial abnormalities in most patients. There are jaw and tooth deformities. There may be extra teeth or small and thin teeth roots.

Due to these deformities snoring is common. In addition there may be feeding difficulties and drooling as well.

Anosmia

There may be a partial or complete loss of the sense of smell (anosmia).

Bardet-Biedl Syndrome Pathophysiology

Bardet-Biedl Syndrome is a genetically inherited condition. It is the result of inheriting mutations or alterations in the genes. At least 14 different genes have been identified that may be mutated or altered in individuals with this syndrome.

Genetics of Bardet-Biedl syndrome

There are 14 different genes that may be altered or mutated in individuals with Bardet-Biedl syndrome. These are commonly termed BBS genes.

These genes code for proteins that are involved in the maintenance and function of cilia of the cells.

What are cilia?

Cilia are finger-like or hair-like structures that are present on the surfaces of many types of cells. These are involved in movement of the cells and different chemical signalling pathways.

Cilia are also vital in perception of sensory input including sight, smell and hearing.

Deformed cilia

Mutations in BBS genes may lead to deformed cilia. Due to these defects there may be disruptions in important chemical signalling pathways. This leads to impaired sensory perceptions. These defective cilia are the basic pathology of Bardet-Biedl syndrome.

BBS1 and BBS10 gene

Around 25% of all cases of this 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 a quarter of patients no specific gene or cause is known.

Genetic changes in a specific BBS gene may exist alone or in combination with mutations in other genes that may modify the course of the disease.

These additional changes of genes along with the original changes in the genes are responsible for the variations of signs and symptoms of Bardet-Biedl syndrome.

Inheritance of Bardet-Biedl syndrome

Bardet-Biedl syndrome is inherited in an autosomal recessive pattern. This means for a child to inherit the condition both parents have to have a single copy of the mutated gene.

These parents do not manifest the symptoms of the condition and typically do not show signs and symptoms of the condition.

Associations with other genetic disorders

There are several genetic disorders that may be associated with Bardet-Biedl syndrome. Commonly other cilia related disorders may be associated with this syndrome. This includes Meckel–Gruber syndrome, Alstrom syndrome, nephronophthisis, polycystic kidney, primary ciliary dyskinesia, retinitis pigmentosa and some forms of retinal degeneration.