SNP Shot: Genomic Insights

Waardenburg syndrome encompasses a collection of inherited genetic disorders affecting hearing and pigmentation (color) of the hair, skin, and eyes. While many individuals with Waardenburg syndrome have normal hearing, a range of hearing loss, from moderate to profound, can occur in one or both ears, and is present at birth (congenital). Characteristic features include very pale blue eyes or heterochromia iridum (eyes of different colors), such as one blue and one brown eye. Some individuals may exhibit sectoral heterochromia, where a single eye displays multiple colors. Distinctive hair features, like a white forelock or premature graying, are also frequently observed. The expression of Waardenburg syndrome is variable, even among members of the same family.

Four distinct types of Waardenburg syndrome are recognized, differentiated by their specific physical characteristics and, in some cases, their underlying genetic cause. Types I and II share similar features; however, widely spaced eyes are almost always present in Type I, but not in Type II. Furthermore, hearing loss is more prevalent in individuals with Type II. Type III, also known as Klein-Waardenburg syndrome, involves limb abnormalities (arms and hands) in addition to the typical hearing loss and pigmentation changes. Type IV, also called Waardenburg-Hirschsprung disease or Waardenburg-Shah syndrome, combines the features of Waardenburg syndrome with those of Hirschsprung disease, a bowel disorder that leads to severe constipation or intestinal obstruction.

Inheritance:

Waardenburg syndrome typically follows an autosomal dominant inheritance pattern. This means that only one copy of the mutated gene is necessary to cause the disorder. In the majority of cases, an affected individual inherits the altered gene from a parent who also has the condition. However, a small number of cases arise from spontaneous new mutations in the gene, occurring in individuals with no family history of Waardenburg syndrome. Some instances of Waardenburg syndrome types II and IV are inherited in an autosomal recessive manner. This implies that both copies of the gene in each cell must carry mutations. In these cases, each parent carries one copy of the altered gene, but typically do not exhibit any symptoms of the condition.