An Overview of Waardenburg Syndrome

Waardenburg syndrome is a genetic disorder characterized by issues that can include patchy areas of depigmentation (albinism) of the skin, eyes, and hair, congenital (from birth) deafness, and a specific structure and spacing of the eyes and nose.

This syndrome affects both males and females and people of all ethnic backgrounds. This disorder is believed to account for 2-5% of all cases of congenital deafness. It is estimated to occur in 1 of 40,000 individuals.

Symptoms and Types

Waardenburg syndrome is divided into four types, based on the physical manifestations of the condition. Individuals are considered to have Waardenburg syndrome type 1 if they have 2 major or 1 major plus 2 minor criteria. Waardenburg syndrome type 2 is defined as having all the features of type 1 except dystopia canthorum.

Major criteria:

• Deaf or hard of hearing from birth
• Pale blue eyes or two different color eyes
• Loss of hair color or a white lock of hair on the forehead
• At least one immediate family member with Waardenburg syndrome
• Dystopia canthorum: inner corner of the eyes displaced to the side

Minor criteria:

• Patches of light or white skin (called leukoderma)
• Eyebrows extending toward middle of face
• Nose abnormalities
• Premature graying of the hair (by age 30)

Waardenburg syndrome type 3, or Klein-Waardenburg syndrome, is similar to type 1 but affects the skeletal muscles, which can include contractures or underdeveloped muscles. Waardenburg syndrome type 4, or Waardenburg-Shah syndrome, is also similar to type 2 but includes Hirschsprung's disease (a gastrointestinal malformation).

Diagnosis

Babies born with Waardenburg syndrome may have hearing loss and may noticeably display the characteristic hair and skin features. However, if the symptoms are mild, Waardenburg syndrome may go undiagnosed unless another family member is diagnosed and all family members are examined.

Formal hearing tests can be used to assess hearing loss. If gastrointestinal symptoms are present, imaging tests (such as abdominal CT) or interventional tests (such as endoscopy) may be necessary.

Treatment

Even within the same family, Waardenburg syndrome can affect people differently. Some individuals might not need treatment while others may need physical therapy, management of the hearing deficit, extra skin protection to avoid sunburns or surgery. Waardenburg syndrome does not usually cause cognitive (thinking and learning) problems or mood or psychiatric effects.

Genetic Counseling

In types 1 and 2, Waardenburg syndrome is inherited in an autosomal dominant pattern, which means that an affected individual has a 50% chance of having an affected child in each pregnancy. Inheritance of types 3 and 4 may follow a more complex pattern.

Several genes have been identified in association with this condition, including mutations in the EDN3, EDNRB, MITF, PAX3, and SOX10 genes.

As symptoms can vary, there is no way to predict whether an affected child will have milder or more severe symptoms than his/her parent but genetic counseling can help assess the risk of passing Waardenburg syndrome on to a child.