Understanding Velo-Cardio-Facial Syndrome (VCFS)

Related: VCFS

by Dr. Robert Shprintzen
Tuesday, March 24, 2009

Velo-cardio-facial syndrome, usually called VCFS for convenience, is listed as a rare disease because it occurs in less than 200,000 people in the United States. This is the equivalent of a population prevalence of 1 in every 1500 people. However, VCFS is one of the most common multiple anomaly syndromes in humans, second only to Down syndrome in frequency. VCFS is found in 1 in every 2000 people in the U.S. although the frequency at birth is undoubtedly higher. VCFS is also known by a number of other names, including Shprintzen syndrome, DiGeorge syndrome, 22q11 deletion syndrome, conotruncal anomalies face syndrome in Japan, and Sedlackova syndrome in Eastern Europe. All of these names describe the same genetic disorder. VCFS is caused by a deletion of DNA from one copy of chromosome 22 (everyone has two copies of chromosome 22). The deletion results in the loss of 40 genes on one copy of chromosome 22, although copies of those genes are located on the other copy. The absence of these 40 genes from one copy of chromosome 22 can result in a wide variety of problems in newborns and also problems later in life as the child develops. There are a total of nearly 200 possible abnormalities in people who have VCFS although none of these problems occur in 100% of cases. It is also true that no one with VCFS has all 200 abnormalities. In fact, most people with VCFS will manifest a relatively small number of these problems, perhaps 15 or 20, and many of them are relatively minor problems. Congenital heart disease is most often the finding that leads doctors to make the diagnosis of VCFS. This diagnosis is most frequently made using a genetic test known as FISH (fluorescent in situ hybridization) which is essentially 100% accurate. In other words, if the test shows that the deletion is present, then the person has VCFS. If the test fails to show the deletion, then the person does not have VCFS.

The most common problems associated with VCFS include the following:

• Congenital heart disease
• Severe speech problems, often associated with dysfunction of the palate
• Early feeding problems
• Immune disorders
• Mild developmental delay
• Learning disabilities
• Behavioral problems
• Endocrine problems

In the adult life, a number of problems can develop that require attention, such as thyroid problems and osteopenia, but what concerns many people is an increased frequency of mental illness in people with VCFS. However, the majority of people with VCFS do not have severe mental illness. The challenge for researchers is to understand how the deletion of these genes causes all of the problems associated with VCFS so that effective treatments can be implemented. Researchers are making great strides in solving these problems and treatments are becoming more effective everyday.

In reviewing the common problems associated with VCFS, people should be aware of the following findings:

Congenital heart disease - approximately 70% of people with VCFS have some type of congenital abnormality of the heart or its major blood vessels, such as the aorta, pulmonary artery, or subclavian arteries. In the large majority of cases, these types of heart problems are surgically correctable with very good outcomes. The most common form of congenital heart disease in VCFS is a ventricular septal defect, an opening between heart chambers. In some cases, this type of septal defect closes on its own and in other cases surgical repair is required. More severe abnormalities of the heart may include an interrupted aortic arch, truncus arteriosus, and tetralogy of Fallot. It is interesting to note that the majority of children born with an interrupted aortic arch, type B have VCFS. Therefore, children with these more severe forms of congenital heart disease are typically screened or VCFS. Surgical repair of these heart problems ranges from relatively simple to very extensive and hospital stays may vary from approximately one week to several weeks. In some rare cases when pulmonary atresia is present, recovery can be much more difficult and problematic. In most cases, definitive repair of these are problems is accomplished and there are relatively few long-lasting effects of this type of surgery.