Wiskott-Aldrich Syndrome

Overview :

WAS was named for the two physicians who first reported the disorder. In 1937, Dr. A. Wiskott, a physician working in Munich, described two affected boys of German ancestry who had repeated infections, a skin rash, and poor blood-clotting ability. Nearly twenty years later, Dr. R.A. Aldrich reported similar symptoms in members of an American family of Dutch ancestry. WAS is inherited as an X-linked genetic disorder and will therefore only affect males. The gene responsible for WAS is located on the short arm of the X chromosome. Since males have only one X chromosome they only have one copy of the gene. If that copy carries the abnormal gene, they will have WAS. In contrast, females have two X chromosomes. They will have a normal copy of the gene on one chromosome even if an abnormal gene is on the other because the abnormal gene is very rare. The normal copy on one X chromosome is usually sufficient to prevent females from having WAS. However, women who have one abnormal copy of the WAS gene are designated as carriers. While they will not have WAS, they have a 50% risk of passing the gene to each of their sons who will have WAS. Carrier females also have a 50% risk of passing the defective copy of the gene to their daughters who also become carriers. Researchers identified the gene for WAS in 1994 and pinpointed its location on the short arm of the X chromosome. As of 2000, over 100 different mutations have been found in the gene among WAS patients. The fact that there are many mutations many explain some of the variability of symptoms among boys with WAS. However, even within the same family, affected individuals with the identical WAS gene mutation may have different degrees of severity of the disease. The mild form, X-linked thrombocytopenia, is also caused by mutations in this same gene. The WAS syndrome affects one in every 250,000 male children and occurs worldwide. In the year 2000, scientists estimated that about 500 Americans have WAS.