Hypohidrotic ectodermal dysplasias: phenotypic and genotypic findings in 32 cases

Abstract

Hypohidrotic ectodermal dysplasias are a genetic condition affecting ectoderm-derived structures such as hair, teeth, nails, and sweat glands, resulting from variations in the EDA, EDAR, EDARADD, and WNT10A genes. This study examined 32 cases from 25 unrelated families from Türkiye, identifying seven novel variants in the EDA, EDAR, and WNT10A genes. The distribution of genetic alterations across the cohort revealed that 44% of the families (11/25) harbored variants in EDA, whereas EDAR and WNT10A variants were identified in 32% (8/25) and 24% (6/25) of families, respectively. Clinical evaluation revealed the characteristic hypohidrotic ectodermal dysplasia triad of hypotrichosis, hypodontia, and hypohidrosis was observed in 87.5% of cases, along with other symptoms such as dry skin, atopic dermatitis, and developmental delays. All cases presented with hair, eyebrow, and eyelash abnormalities, ranging in severity from subtle thinning to marked hypotrichosis. Among the cohort, one case exhibited severe atopic dermatitis as the predominant symptom. Targeted next-generation sequencing and clinical exome sequencing were employed to determine the genetic basis of the condition, emphasizing the importance of early diagnosis for targeted interventions. This study expands the genetic and phenotypic spectrum of hypohidrotic ectodermal dysplasia, presenting a comprehensive overview of molecular findings and genotype–phenotype correlations in the population from the Turkish population.