Research

Genetics Program

Dr. Colleen A. Morris conducts research on genotype/phenotype correlation of Williams syndrome and duplication chromosome 7 (Dup7) with collaborators at the University of Louisville and Toronto Sick Childrens. The Principal Investigators include psychologist, Carolyn B. Mervis Ph.D. at the University of Louisville and Lucy Osborne, Ph.D. in Toronto. They are investigating the genetic, neurological, behavioral and psychological aspects of Dup7 and its correlation with autism.

What is Williams syndrome?

Williams syndrome is a contiguous gene disorder that results from a submicroscopic deletion of chromosome 7q11.23. This region is 1-2 megabases in length and includes the elastin gene. In 1993, Dr. Morris and collaborators discovered that Williams syndrome is the result of deletion of the elastin gene on one of the number 7 chromosomes. This deletion usually occurs sporadically. Individuals who have the deletion, however, have a 50% chance of passing that deletion on to their offspring.

The research group also determined that mutation in the elastin gene results in an autosomal dominant disorder, supravalvar aortic stenosis. Individuals who have supravalvar aortic stenosis without the other manifestations of Williams syndrome typically have mutations in the elastin gene or very small deletions of the elastin gene region. Williams syndrome is a condition that occurs in 1/20,000 births. Most children with Williams syndrome are born into families who have not had any other children born with Williams syndrome or any individuals with congenital heart disease.

In family studies, the elastin gene has been normal in parents of children with sporadic Williams syndrome, suggesting that the deletion (loss) of chromosome material occurred accidentally in the egg or the sperm cell that resulted in this particular child. Therefore, couples who do not have a positive family history and who have no signs of Williams syndrome, are at low risk to have another child with Williams syndrome. However, individuals who have Williams syndrome have a 50% risk of having a child with Williams syndrome with each pregnancy.

Williams syndrome is characterized by particular facial features. These facial features include periorbital fulness, a stellate pattern of the iris, a low nasal root, broad nasal tip, flat malar region, long smooth philtrum, wide mouth and dental malocclusion.

Many birth defects are possible with Williams syndrome--the most common is supravalvar aortic stenosis. This cardiac defect is present in many children with Williams syndrome and 80% of children with Williams syndrome have a murmur. It has been shown that the supravalvar aortic stenosis may worsen with time as the child grows if the stenotic area does not increase in size at the same rate. Therefore, it is recommended that all children with Williams syndrome have a baseline cardiac evaluation which includes 4 limb blood pressures and echocardiogram with doppler and then be followed at appropriate intervals by a pediatric cardiologist. In addition, high blood pressure is very common in Williams syndrome. It usually appears in teenage years. Usually the blood pressure is higher in the right arm than in the left due to the supravalvar aortic stenosis. Therefore, it is recommended that the child with Williams syndrome have blood pressure taken on a yearly basis by a pediatrician. Other arteries may also be narrowed.

Eye problems in Williams syndrome include strabismus (cross eyes) and hyperopia (farsightedness). A baseline ophthalmologic evaluation is recommended. Recurrent ear infections are common in young children and ENT referral may be necessary. Thyroid studies should done at the time of diagnosis, and repeated by age five years to screen for hypothyroidism.

Inguinal and unbilical hernias are common and occur in about 50% of individuals with Williams syndrome. Surgery is necessary to correct the inguinal hernias, but is not required for umbilical hernia. Gastrointestinal complaints are also quite common and include constipation and vomiting in infancy and abdominal pain in adults. Some of these symptoms are due to hypercalcemia which can occur in Williams syndrome.

The hypercalcemia is usually easiest to detect in infancy. However, even past the infancy period, a screening test should be performed that includes serum calcium and a random urine sample to determine a calcium to creatinine ratio. The cause of the calcium abnormality in 50% of infants with Williams syndrome is unknown. Most individuals with Williams syndrome in the United States are not treated for calcium problems unless they are truly hypercalcemic. If the total calcium is normal, then urine calcium/creatinine ratio should be checked every few years.

Kidney problems can occur in Williams syndrome. Bladder diverticuli and chronic urinary infections are quite common. Enuresis is also a common problem with Williams syndrome and may in fact be related to the hypercalcemia and increased urinary output. However, this is a problem which usually resolves with time. A baseline renal and bladder ultrasound should be done on every Williams syndrome patient. Urinalysis should be checked every two years.

Joint limitations are also a common finding in older children and adults with Williams syndrome. Young children usually have loose joints. A certain percentage, roughly 12-15% of individuals with Williams syndrome do have true radio ulnar synostosis. Treatment is usually not recommended though this should be taken into account when planning educational and vocational training. Joint limitations is usually progressive and primarily involves the lower extremities. Therefore, physical therapy or at least passive range of motion exercises at home are strongly recommended.

All individuals with Williams syndrome have a learning disability. The average IQ for individuals with Williams syndrome is in the mild range of intellectual disability. However, individuals with more severe impairment and individuals with normal intelligence have been reported with Williams syndrome. Therefore, each child with Williams syndrome requires special education. The most common disability is in the area of visual motor integration and, therefore, it is recommended that auditory learning, which is a strength in Williams syndrome, should be utilized most frequently. Occupational therapy is an important component to the educational program in Williams syndrome. Attention deficit disorder is extremely common in Williams syndrome and often requires mediation. Psychometric evaluation should be performed at regular intervals. Some older children and adults have had problems with anxiety. Teaching "self calming" and relaxation techniques to preadolescent and adolescent children may be of benefit, especially if music tapes are used.

More information is available at the Williams Syndrome Association Website. Dr. Morris has also authored a current review of Williams syndrome.