A Novel Homozygous CDH3 Variant Associated with Ectodermal Dysplasia and Bilateral Central Macular Dystrophy Without Ectrodactyly

Abstract

Ectodermal dysplasia with macular dystrophy (EDMD) is a rare genetic disorder caused by pathogenic variants in the CDH3 gene, characterized by variable involvement of ectoderm-derived tissues and retinal structures. We report the clinical and molecular features of a 12-year-old girl born to consanguineous parents, presenting with severe hypotrichosis, generalized xerosis, trachyonychia, early dental eruption, and progressive visual acuity decline since childhood due to bilateral central macular dystrophy. Notably, no limb anomalies were observed, distinguishing this presentation from classical EEM syndrome. Whole-exome sequencing identified a novel homozygous splice-site variant in CDH3 (NM_001793.6:c.867+1G>A), which was confirmed by Sanger sequencing. This case highlights the phenotypic variability of CDH3-related disorders and expands the recognized clinical spectrum, showing that macular and ectodermal involvement can occur independently of limb anomalies. These findings emphasize the importance of molecular diagnosis, genotype–phenotype correlation, genetic counseling, and multidisciplinary follow-up, including dermatology, ophthalmology, pediatric dentistry, and child psychiatry.