Bardet-Biedl syndrome Health Article

Definition

Bardet-Biedl syndrome (BBS) is a condition that primarily affects vision, kidney function, limb development, growth, and intelligence.

Description

BBS expresses itself differently from person to person, even among members of the same family. However, certain features frequently appear.

Genetic profile

BBS is a genetically heterogeneous condition; this means that it has more than one known genetic cause. One of these causes is a mutation in the MKKS gene, located on chromosome 20. When working properly, this gene appears to produce a chaperonin, a factor needed to process proteins. Without the chaperonin, the proteins cannot work properly.

Using linkage analysis, researchers have connected some BBS cases to other chromosomes. Linkage analysis is a method of finding mutations based on their proximity to previously identified genetic landmarks. As of February 2001, the specific genes responsible for these BBS cases remain unknown. However, several potential locations of BBS genes have been recognized. These sites are named for the number of the chromosome on which they are found, the arm of the chromosome ("q" for long arm, "p" for short arm), region of the arm, and band within the region. For example, "11q13" means chromosome number 11, long arm, region 1, band 3. In studies of families with BBS, researchers have found that a significant number of cases link either to 11q13, 15q22, or 16q21. In other families, researchers have linked BBS to either 2q31, 3p12, or 20p12. This last site is the location of the MKKS gene.

Regardless of the site involved, BBS displays an autosomal recessive inheritance pattern. This means that the condition occurs only when an individual inherits two defective copies of a BBS gene. If one copy is normal, the individual does not have BBS. This individual is called a carrier of BBS and can pass the gene on to the next generation.

Research indicates that people who inherit one abnormal BBS gene and one normal gene may be at risk for some of the health problems seen in BBS. Compared to the general population, these BBS gene carriers are more likely to develop high blood pressure, diabetes mellitus, and kidney disease, including kidney cancer.

Demographics

BBS affects people around the world. However, it is most common in the Middle East, especially in the Arab and inbred Bedouin populations of Kuwait. In these groups, it may affect as many as one in 13,500 individuals. The incidence is almost as high in Newfoundland, where as many as one in 16,000 individuals has BBS. Outside of these areas, researchers estimate that BBS affects only one in 160,000 people.

The specific genetic cause of BBS differs by family and geographic location. For example, in the Middle East, BBS appears to link to 16q21 or 3p12. However, in patients of European descent, BBS appears to link to 11q13 or 15q22.

Signs and symptoms

If the newborn with BBS has finger or toe abnormalities, these are apparent at birth. However, these defects have a variety of congenital causes, meaning they originated during development of the fetus and were not inherited. For this reason, medical care providers may not immediately suspect BBS. It becomes a consideration as the child develops and additional abnormalities emerge. In boys, genital abnormalities become evident soon after birth. In almost all patients, obesity and retinal degeneration begin in early childhood. Learning disabilities, if present, are identified in school-aged children, if not earlier. Failure to menstruate leads to diagnosis of some adolescent girls. Infertility brings some young adults to medical attention. Kidney disease is progressive and may not become obvious until adulthood.

Due to progressive degeneration of the retina, vision damage occurs in all patients. Specific vision defects include poor night vision during childhood, severe myopia (nearsightedness), glaucoma, and cataracts. A few patients suffer from retinitis pigmentosa, a condition in which the field of vision progressively narrows. Most individuals affected with BBS are blind by age 30.

Many infants with BBS are born with a kidney defect affecting kidney structure, function, or both. The specific abnormality varies from patient to patient and may be aggravated by lifelong obesity, another common problem for BBS patients. The complications of obesity, such as high blood pressure (hypertension) and insulin-resistant diabetes mellitus, contribute to kidney disease.

BBS patients may have extra fingers or toes (polydactyly), short fingers (brachydactyly), or broad, short feet. Some patients have a combination of all three of these features. Alternately, polydactyly may be limited to one limb, hands only, or feet only. Syndactyly, the fusion of two or more fingers or toes, may also occur. In some BBS families, all affected members display at least some of these limb abnormalities.

Many individuals with BBS have genital abnormalities. Most boys with BBS have a very small penis and some also have undescended testes. Men with BBS are usually unable to have children. In women with BBS, the genitalia, ovaries, fallopian tubes, and uterus may or may not be underdeveloped. The vagina may not be completely formed. Though some women with BBS do not menstruate, others menstruate irregularly, and some women are able to have children. In both sexes, there may be birth defects in the urinary or gastrointestinal tract.

Some research indicates that people with BBS have characteristic facial features, including a prominent forehead, deep-set eyes, flat nasal bridge, and thin upper lip. Teeth are small and crowded, and a high, arched palate is common.

Occasionally, individuals with BBS have liver disease or heart abnormalities.

In addition to the physical effects of the condition, intelligence is sometimes affected. While some BBS patients show normal intelligence, others have mild to moderate learning disabilities. These patients are often developmentally delayed—they are slower than most children to walk, speak, or reach other developmental milestones. Difficulty with language and comprehension may continue into adulthood. In a few people with BBS, more severe mental retardation occurs. In some patients, vision handicap and developmental delay appear to be related.

Some parents report that their children with BBS have behavioral problems that continue into adulthood. These include lack of inhibition and social skills, emotional outbursts, and obsessive-compulsive behavior. Most people with BBS prefer fixed routines and are easily upset by a change in plans.