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Waardenburg Syndrome: A Rare Pigment Condition

Author: Ellie Wang

Editors: Ken Saito and Peggy Yang

Artists: Serena Yung

Waardenburg syndrome is a rare genetic condition that affects approximately 1 in 42,000 people worldwide. It is categorized into four different types based on the different symptoms and causes, though there are variations in pigmentation of the hair, skin, and eyes. Type I and II are the most common, while Type III and Type IV are rarer. The symptoms of those affected by this syndrome vary widely from person to person, even among immediate family members. Most people inherit the syndrome in an autosomal dominant pattern, which means that only one copy of the mutated gene is needed, instead of two.

First, most cases of Type I are characterized by abnormal vision and tear production, heterochromia, patches of pigment loss of the skin and hair (hypopigmented patches), a white part of the hair above the forehead (poliosis), multiple colors in a single iris, and hearing loss from birth (congenital hearing loss). Having widely spaced eyes is also unique to Type I. This type is caused by mutations in the PAX3 gene, which causes PAX3 proteins to lose their ability to regulate the activity of other genes. Thus, melanocytes, or pigment cells, don’t develop in certain areas of the body, including the inner ear, resulting in loss of pigmentation and hearing. Additionally, the mutations impede the development of some bones in the head and face, causing widely set eyes.

Similarly, people with Type II Waardenburg syndrome can have heterochromia, hypopigmented patches, poliosis, multiple colors in a single iris, and congenital hearing loss for the same reason. However, those with Type II are more likely to suffer from hearing loss than those with Type I, both congenital (from birth) and progressive (from worsening health). Type II has subtypes A through E, caused by various mutations on different genes, respectively. In contrast to the majority of cases, subtype 2D is inherited in an autosomal recessive manner. This means that two copies of the mutated gene need to be inherited in order to be affected by this type.

Next, Type III, also known as Klein-Waardenburg syndrome, is classified by changes in pigmentation, hearing loss, and abnormalities of the arms and hands. Joints in the aforementioned body parts are stiff, and those affected cannot access the full range of motion. Though the mutations have distinct characteristics, Type I and Type III are both caused by mutations of the PAX3 gene.

Finally, Type IV, also called Waardenburg-Shah syndrome or Waardenburg-Hirschsprung disease, is characterized by the typical loss in pigmentation and hearing. People with Waardenburg syndrome Type IV also suffer from Hirschsprung disease, an intestinal disorder involving constipation and intestinal obstruction. Three subtypes of this disease exist: A, B, and C. Although most Type IV is inherited through autosomal dominant means, some seem to be autosomal recessive cases.

As of now, there is no cure to Waardenburg syndrome, though there are supportive treatments to improve quality of life and ease symptoms. Hopefully, as medical science progresses, treatments for Waardenburg syndrome will be developed and provide relief for those it impacts.



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