Williams Syndrome | Research & Encyclopedia Articles

Williams Syndrome

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.

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 and change over time.

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 individual 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.

Williams syndrome occurs in 1/20,000 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.

Williams syndrome is a multi-system disorder. In addition, to distinct facial features individuals with Williams syndrome can have cardiovascular, growth, joint, and other physical problems. They also share unique personality traits and have intellectual differences. Infants with Williams syndrome are often born small for their family and 70% are diagnosed as failure to thrive during infancy. These growth problems continue throughout the life of a person with Williams syndrome and most individuals with Williams syndrome have short stature (height below the third percentile). Infants with William syndrome can also be extremely irritable and have "colic-like" behavior. This behavior is thought to be due to excess calcium in the blood (hypercalcemia). Other problems that can occur in the first years include strabismus (crossed eyes), ear infections, chronic constipation and eating problems.

Individuals with Williams syndrome can have distinct facial features sometimes described as "elfin" or "pixie-like." While none of these individual facial features are abnormal, the combination of the different features is common for Williams syndrome. Individuals with Williams syndrome have a small upturned nose, a small chin, long upper lip with a wide mouth, small widely spaced teeth and puffiness around the eyes. As an individual gets older, these facial features become more pronounced.

People with Williams syndrome often have problems with narrowing of their heart and blood vessels. This is thought to be due to the deletion of the elastin gene and is called elastin arteriopathy. Any artery in the body can be affected but the most common narrowing is seen in the aorta of the heart. This condition is called supravalvar aortic stenosis (SVAS) and occurs in approximately 75% of individuals with Williams syndrome. The degree of narrowing is variable. If left untreated, it can lead to high blood pressure, heart disease and heart failure. The blood vessels that lead to the kidney and to other organs can also be affected.

Deletions of the elastin gene are also thought to be responsible for the loose joints of some children with Williams syndrome. As individuals with Williams syndrome age, their heel cords and hamstrings tend to get tight which can lead to a stiff awkward gait and curving of the spine.

Approximately 75% of individuals with Williams syndrome have mild mental retardation. They also have a unique cognitive profile (unique learning abilities and disabilities). This cognitive profile is independent of their I.Q. Individuals with Williams syndrome generally have excellent language and memorization skills. They can have extensive vocabularies and can develop a thorough knowledge of a topic of interest. Many individuals are also gifted musicians. Individuals with Williams syndrome have trouble with concepts that rely on visuospatial ability. Because of this, many people with Williams syndrome have trouble with math, writing and drawing.

The diagnosis of Williams syndrome is usually made by a physician familiar with Williams syndrome and based upon a physical examination of the individual and a review of their medical history. It is often made in infants after a heart problem (usually SVAS) is diagnosed. In children without significant heart problems, the diagnosis may be made after enrollment in school when they are noted to be "slow-learners." While a tentative diagnosis can be made based upon physical examination and medical history, the diagnosis is confirmed by a DNA test.

Because Williams syndrome is caused by a deletion of genetic material from the long arm of chromosome 7, a specific technique called fluorescent in situ hybridization testing, or FISH testing, can determine whether there is genetic material missing. A FISH test will be positive (detect a deletion) in over 99% of individuals with Williams syndrome. A negative FISH test for Williams syndrome means that no genetic material is missing from the critical region on chromosome 7q11.

Prenatal testing (testing during pregnancy) for Williams syndrome is possible using the FISH test on DNA sample obtained by chorionic villi sampling (CVS) or by amniocentesis. Chorionic villi sampling is a prenatal test that is usually done between 9 to 11 weeks of pregnancy and involved removing a small amount of tissue from the placenta. Amniocentesis is a prenatal test that is usually performed between 16-19 weeks of pregnancy and involves removing a small amount of the amniotic fluid that surrounds the fetus. DNA is obtained from these samples and tested to see if the deletion responsible for Williams syndrome is present. While prenatal testing is possible, it is not routinely performed. Typically, the test is only done if there is a family history of Williams syndrome.