WNT10A

Several mutations in the WNT10A gene have been found to cause hypohidrotic ectodermal dysplasia, the most common form of ectodermal dysplasia. Starting before birth, ectodermal dysplasias result in the abnormal development of the skin, hair, nails, teeth, and sweat glands. Hypohidrotic ectodermal dysplasia is characterized by a reduced ability to sweat (hypohidrosis), sparse scalp and body hair (hypotrichosis), and several missing teeth (hypodontia) or teeth that are malformed. WNT10A gene mutations account for about 5 percent of all cases of hypohidrotic ectodermal dysplasia.

Most of the WNT10A gene mutations associated with hypohidrotic ectodermal dysplasia change single protein building blocks (amino acids) in the WNT10A protein, which impairs its function. The resulting shortage of functional WNT10A protein disrupts Wnt signaling during the development of ectodermal tissues, particularly the teeth.

Hypohidrotic ectodermal dysplasia can result from mutations in several genes. When the condition is caused by WNT10A gene mutations, its features are more variable than when the condition is caused by mutations in any other gene. Signs and symptoms range from mild to severe, and mutations in this gene are more likely to cause all of the permanent teeth to be missing.

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Mutations in the WNT10A gene have been reported to cause several other, rare forms of ectodermal dysplasia, including odonto-onycho-dermal dysplasia (OODD) and Schopf-Schulz-Passarge syndrome (SSPS). OODD is characterized by dry hair, missing teeth, a smooth tongue, fingernail and toenail abnormalities, thickened skin on the palms of the hands and soles of the feet (palmoplantar keratoderma), and increased sweating (hyperhidrosis) of the palms and soles. The major features of SSPS include missing teeth, hypotrichosis, palmoplantar keratoderma, and fluid-filled sacs (cysts) on the edges of the eyelids.

WNT10A gene mutations are also frequently associated with a condition called nonsyndromic tooth agenesis. This condition causes one or more teeth not to form. Although missing teeth is a common feature of ectodermal dysplasias, "nonsyndromic" suggests that in these cases tooth agenesis occurs without the other signs and symptoms of those conditions.

More than 70 WNT10A gene mutations have been identified in people with various forms of ectodermal dysplasia or nonsyndromic tooth agenesis. Most of these mutations change single amino acids in the WNT10A protein, which impairs its function. The resulting shortage of functional WNT10A protein disrupts Wnt signaling during the development of ectodermal tissues, including the skin, hair, nails, teeth, and sweat glands. Researchers are working to determine why mutations in this gene can cause several different disorders.