Williams Syndrome Health Article

Definition

Williams syndrome is a genetic disorder caused by a deletion of a series of genes on chromosome 7q11. Individuals with Williams syndrome have distinctive facial features, mild mental retardation, heart and blood vessel problems, short stature, unique personality traits, and distinct learning abilities and deficits.

Description

Williams syndrome, also known as Williams Beuren syndrome, was first described in 1961 by Dr. J. C. P. Williams of New Zealand. At that time it was noted that individuals with Williams syndrome had an unusual constellation of physical and mental findings. The physical features include a characteristic facial appearance, heart and cardiovascular problems, high blood calcium levels, low birth weight, short stature, and other connective tissue abnormalities. The intellectual problems associated with Williams include a mild mental retardation and a specific cognitive profile. That is, individuals with Williams syndrome often have the same pattern of learning abilities and disabilities, as well as many similar personality traits.

The findings in Williams syndrome are variable—that is, not all individuals with Williams syndrome will have all of the described findings. In addition to being variable, the physical and mental findings associated with Williams syndrome are progressive—they change over time.

Genetic profile

Williams syndrome is a genetic disorder due to a deletion of chromosome material on the long arm of chromosome 7. A series of genes are located in this region. Individuals with Williams syndrome may have some or all of these genes deleted. Because of this, Williams syndrome is referred to as a contiguous gene deletion syndrome. Contiguous refers to the fact that these genes are arranged next to each other. The size of the deletion can be large or small, which may explain why some individuals with Williams syndrome are more severely affected than others. If you think of these genes as the letters of the alphabet, some individuals with Williams syndrome are missing A to M, some are missing G to Q and others are missing A to R. While there are differences in the amount of genetic material that can be deleted, there is a region of overlap. Everyone in the above example was missing G to M. It is thought that the missing genes in this region are important causes of the physical and mental findings of Williams syndrome.

Two genes in particular, ELN and LIMK1, have been shown to be important in causing some of the characteristic symptoms of Williams syndrome. The ELN gene codes for a protein called elastin. The job of elastin in the human body is to provide elasticity to the connective tissues such as those in the arteries, joints and tendons. The exact role of the LIMK1 gene is not known. The gene codes for a substance known as lim kinase 1 that is active in the brain. It is thought that the deletion of the LIMK1 gene may be responsible for the visuospatial learning difficulties of individuals with Williams syndrome. Many other genes are known to be in the deleted region of chromosome 7q11 responsible for Williams syndrome and much work is being done to determine the role of these genes in Williams syndrome.

Williams syndrome is an autosomal dominant disorder. Genes always come in pairs and in an autosomal dominant disorder, only one gene need be missing or altered for an individual to have the disorder. Although Williams syndrome is an autosomal disorder, most individuals with Williams syndrome are the only people in their family with this disorder. When this is the case, the chromosome deletion that causes Williams syndrome is called de novo. A de novo deletion is one that occurs for the first time in the affected individual. The cause of de novo chromosome deletions is unknown. Parents of an individual with Williams syndrome due to a de novo deletion are very unlikely to have a second child with William syndrome. However, once an individual has a chromosome deletion, there is a 50% chance that they will pass it on to their offspring. Thus individuals with Williams syndrome have a 50% chance of passing this deletion (and Williams syndrome) to their children.

Demographics

Williams syndrome occurs in one in 20,000 births. Because Williams syndrome is an autosomal dominant disorder, it affects an equal number of males and females. It is thought that Williams syndrome occurs in people of all ethnic backgrounds equally.