Hypohidrotic ectodermal dysplasia (HED) is a genetic disorder of ectoderm development characterized by malformation of ectodermal structures such as skin, hair, teeth and sweat glands. It comprises three clinically almost indistinguishable subtypes with impaired sweating as the key symptom: Christ-Siemens-Touraine (CST) syndrome (X-linked), autosomal recessive (AR), and autosomal dominant (AD) HED, as well as a fourth rare subtype with immunodeficiency as the key symptom (HED with immunodeficiency)
HED is due to mutations in genes of the ectodysplasin/NF-κB pathway, necessary for the correct development of several ectodermal structures. Mutations in EDA (Xq12-q13.1), encoding the epithelial morphogen ectodysplasin-A of the tumor necrosis factor family, cause the CST syndrome. Mutations in EDAR (2q13), encoding the Ectodysplasin-A receptor, or EDARADD(1q42.3), encoding the EDAR-associated death domain (EDARADD) protein, cause both AR and AD HED. IKBKG (Xq28) mutations cause HED with immunodeficiency. WNT10A, TRAF6, NFKBIA or EDA2R mutations may be responsible for some HED cases.
