First Genetically Confirmed X-linked Hypohidrotic Ectodermal Dysplasia in Nepal: Diagnostic Odyssey and Mismanaged Hyperthermia

Abstract

Hypohidrotic ectodermal dysplasia is a rare inherited disorder affecting ectoderm-derived tissues and is characterized by hypohidrosis, hypotrichosis, and hypodontia or oligodontia. We report the first molecularly confirmed case of X-linked hypohidrotic ectodermal dysplasia in Nepal. An 8-year-old boy from Kohalpur presented with recurrent fever since infancy, inability to sweat, sparse scalp hair, and severe oligodontia. Targeted exome sequencing identified a hemizygous pathogenic variant in the ectodysplasin A gene (c.466C>T; p.Arg156Cys), while no pathogenic variants were detected in the ectodysplasin A receptor or the ectodysplasin A receptor–associated death domain. His sister had mild dental anomalies, suggesting a symptomatic carrier phenotype. This case highlights the value of molecular diagnosis in confirming clinically suspected hypohidrotic ectodermal dysplasia, enabling accurate genetic counseling, family screening, and appropriate long-term management. It also demonstrates the feasibility of advanced genetic testing in Nepal through international laboratory collaboration.