X-linked hypohidrotic ectodermal dysplasia (HED) is a rare genetic disorder caused by pathogenic variants in the EDA gene and characterized by variable involvement of ectoderm-derived tissues. The aim of this study is to describe the clinical and molecular features of a Moroccan family affected by X-linked HED, with particular emphasis on the role of X-chromosome inactivation in phenotypic variability among female carriers. Clinical and genetic investigations identified the pathogenic EDA variant c.467G>A (p.Arg156His) in an affected boy and his heterozygous mother. Notably, the mother exhibited a more severe ectodermal phenotype than typically observed in female carriers. This observation highlights the likely impact of skewed X-chromosome inactivation on disease expression and underscores its importance for genotype–phenotype interpretation, genetic counseling, and multidisciplinary care.
Hammouch et al. (Mon,) studied this question.