SOX10

Variants (also known as mutations) in the SOX10 gene have been identified in people with Waardenburg syndrome type II and type IV (also known as Waardenburg-Hirschsprung disease or Waardenburg-Shah syndrome). Both types of Waardenburg syndrome are characterized by changes in skin, hair, and eye coloring and hearing loss. People with type IV also have an intestinal disorder called Hirschsprung disease that causes severe constipation or intestinal blockage. 

Most SOX10 gene variants lead to the production of an abnormal version of the SOX10 protein or prevent the gene from making any protein. An abnormal or missing SOX10 protein cannot control genes that signal neural crest cells to become specific cell types. As a result, enteric nerves and melanocytes do not form normally during embryonic development. Missing enteric nerves in certain parts of the intestine cause the signs and symptoms of Hirschsprung disease. A lack of melanocytes affects the coloring of skin, hair, and eyes and causes the hearing loss characteristic of Waardenburg syndrome.

Researchers have found that variants in the SOX10 gene also cause a similar disorder known as peripheral demyelinating neuropathy, central demyelinating leukodystrophy, Waardenburg syndrome, and Hirschsprung disease (PCWH). This rare condition is a variant of Waardenburg syndrome type IV that also affects other parts of the nervous system. Like variants that cause other types of Waardenburg syndrome, the variants involved in PCWH lead to the production of an abnormal version of the SOX10 protein that is unable to direct the activity of other genes.

MedlinePlus Genetics provides information about Hirschsprung disease

MedlinePlus Genetics provides information about Kallmann syndrome