A clinical case of X-linked hypohidrotic ectodermal dysplasia caused by an Xq13.1 duplication affecting the EDA gene

X-linked hypohidrotic ectodermal dysplasia (XLHED; Christ–Siemens–Touraine syndrome, ICD-10: Q82.4) is the most common type of ectodermal dysplasia, caused by genetic disorders of ectodermal derivatives. The condition significantly impacts patients’ quality of life, presenting with a classic triad of hypohidrosis, hypotrichosis and hypodontia, which creates a risk of impaired thermoregulation and necessitates complex dental rehabilitation. The molecular basis of the disease lies in alterations of the EDA gene, which encodes ectodysplasin A. This protein belongs to the tumor necrosis factor (TNF) family and plays a critical signaling role in ectodermal-mesenchymal interactions during embryonic development. The present case report describes a boy with an XLHED phenotype caused by a previously unreported structural rearrangement. Whole-genome sequencing (WGS) identified a ~397.3 kb microduplication at the Xq13.1 locus directly involving the EDA gene. Comprehensive bioinformatic analysis ruled out additional pathogenic or likely pathogenic variants in other genes that could account for the patient’s phenotype. The Xq13.1 microduplication was confirmed in both the proband and his mother using quantitative real-time PCR (qPCR). Androgen receptor (AR) gene methylation analysis in the mother revealed a random X-chromosome inactivation (74/26 %), explaining her asymptomatic carrier status. The proband’s clinical manifestations were also compared to those of literature-reported patients with overlapping genomic rearrangements. Based on international and Russian guidelines for the interpretation of massively parallel sequencing data, the identified variant was classified as pathogenic. Identification of this structural rearrangement expands the known mutational spectrum of the EDA gene. Establishing a precise molecular genetic diagnosis in this family is critical not only for disease verification but also for optimizing patient management through a multidisciplinary approach. Furthermore, it enables comprehensive genetic counseling, identification of female carriers among relatives and the development of timely primary and secondary prevention measures for the disease in this family. 

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