Waardenburg Syndrome

What is Waardenburg syndrome?

Waardenburg syndrome is a group of genetic conditions that can cause hearing loss and changes in colouring (pigmentation) of the hair, skin, and eyes. Although most people with Waardenburg syndrome have normal hearing, moderate to profound hearing loss can occur in one or both ears. People with this condition often have very pale blue eyes or different coloured eyes, such as one blue eye and one brown eye. Sometimes one eye has segments of two different colours. Distinctive hair colouring (such as a patch of white hair or hair that prematurely turns gray) is another common sign of the condition. The features of Waardenburg syndrome vary among affected individuals, even among people in the same family.

The four known types of Waardenburg syndrome are distinguished by their physical characteristics and sometimes by their genetic cause. Types I and II have very similar features, although people with type I almost always have eyes that appear widely spaced and people with type II do not. In addition, hearing loss occurs more often in people with type II than in those with type I. Type III (sometimes called Klein-Waardenburg syndrome) includes abnormalities of the upper limbs in addition to hearing loss and changes in pigmentation. Type IV (also known as Waardenburg-Shah syndrome) has signs and symptoms of both Waardenburg syndrome and Hirschsprung disease, an intestinal disorder that causes severe constipation or blockage of the intestine.

How common is Waardenburg syndrome?

Waardenburg syndrome affects an estimated 1 in 10,000 to 20,000 people. In schools for the deaf, 2 percent to 3 percent of students have this condition. Types I and II are the most common forms of Waardenburg syndrome, while types III and IV are rare.

What genes are related to Waardenburg syndrome?

Mutations in the EDN3, EDNRB, MITF, PAX3, SNAI2, and SOX10 genes cause Waardenburg syndrome.

The genes that cause Waardenburg syndrome are involved in the formation and development of several types of cells, including pigment-producing cells called melanocytes. Melanocytes make a pigment called melanin, which contributes to skin, hair, and eye colour and plays an essential role in the normal function of the inner ear. Mutations in any of these genes disrupt the normal development of melanocytes, leading to abnormal pigmentation of the skin, hair, and eyes and problems with hearing.

Types I and III Waardenburg syndrome are caused by mutations in the PAX3 gene. Mutations in the MITF and SNAI2 genes are responsible for type II Waardenburg syndrome.

Mutations in the SOX10, EDN3, or EDNRB genes cause type IV Waardenburg syndrome. In addition to melanocyte development, these genes are important for the development of nerve cells in the large intestine. Mutations in any of these genes result in hearing loss, changes in pigmentation, and intestinal problems related to Hirschsprung disease.

How do people inherit Waardenburg syndrome?

Waardenburg syndrome is usually inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person has one parent with the condition. A small percentage of cases result from new mutations in the gene; these cases occur in people with no history of the disorder in their family.

Some cases of type II and type IV Waardenburg syndrome appear to have an autosomal recessive pattern of inheritance, which means two copies of the gene in each cell are altered. Most often, the parents of an individual with an autosomal recessive disorder are carriers of one copy of the altered gene but do not show signs and symptoms of the disorder.

What other names do people use for Waardenburg syndrome?

• Waardenburg's Syndrome