The clinical features of the X-linked and autosomal forms of hypohidrotic ectodermal dysplasia can be indistinguishable.
EDA1 gene mutations have been found in 75%-95% of familial hypohidrotic ectodermal dysplasia and about 50% of sporadic cases. Sequencing can detect approximately 95% of EDA1 mutations in affected males. In approximately 10% of patients, large deletions of one or more exons or a deletion of the entire EDA1 gene have been reported. In females, targeted array CGH analysis with exon-level resolution (ExonArrayDx) is performed concurrently with sequencing to evaluate for such intragenic deletions/duplications.
Mutations in the WNT10A gene have been reported in up to 9% of individuals with ectodermal dysplasia and in 25% of individuals with HED who do not have a mutation in the EDA1 gene. A broad spectrum of clinical features has been found in ectodermal dysplasia patients who are compound heterozygous or homozygous for mutations in the WNT10A gene, with the most consistent clinical feature being severe oligodontia of permanent teeth. Other common features include: dry skin, nail dystrophy, abnormal teeth, sparse hair, and hypohidrosis or hyperhidrosis. Approximately 50% of heterozygotes carrying a WNT10A mutation have mild clinical symptoms of ectodermal dysplasia, including abnormal teeth and nails.
Mutations in the EDAR gene are responsible for both autosomal dominant and autosomal recessive forms of HED. Mutations in this gene have been reported in about 7% of individuals with HED and in up to 25% of individuals with HED who do not have a EDA1 gene mutation. The clinical features are clinically indistinguishable from the X-linked form (EDA1) and include fine, sparse and light-colored scalp and body hair (hypotrichosis), decreased ability to sweat leading to heat intolerance, and missing, conical or peg shaped teeth. The facial features are characterized by dark pigmented skin surrounding the eyes, saddle nose and full lips. Males and females are equally affected.