A Novel Homozygous CDH3 Variant Associated with Ectodermal Dysplasia and Bilateral Central Macular Dystrophy Without Ectrodactyly
Main Article Content
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.
Article Details
This work is licensed under a Creative Commons Attribution 4.0 International License.
References
I. Sprecher E, Bergman R, Richard G, et al. Hypotrichosis with juvenile macular dystrophy is caused by a mutation in CDH3, encoding P-cadherin. Nature Genetics. 2001;29(2):134–136. doi:10.1038/ng716
II. Kjaer KW, Hansen L, Schwabe GC, Marques de Faria AP, Eiberg H, Mundlos S, Tommerup N, Rosenberg T. Distinct CDH3 mutations cause ectodermal dysplasia, ectrodactyly, macular dystrophy (EEM syndrome). Journal of Medical Genetics. 2005;42(4):292–298. doi:10.1136/jmg.2004.027821
III. Vanagaite B, Pasmanik-Chor M, Lurie R, Yeheskel A, Kjaer KW. CDH3-related syndromes: report on a new mutation and overview of the genotype–phenotype correlations. Molecular Syndromology. 2010;1(5):223–230. doi:10.1159/000327156.
IV. Kjaer KW, Hansen L, Schwabe GC, Marques de Faria AP, Eiberg H, Mundlos S, Tommerup N, Rosenberg T. Distinct CDH3 mutations cause ectodermal dysplasia, ectrodactyly, macular dystrophy (EEM syndrome). J Med Genet. 2005;42(4):292–298. doi:10.1136/jmg.2004.027821.
V. Senecky Y, Halpern GJ, Inbar D, Attias J, Shohat M. Ectodermal dysplasia, ectrodactyly and macular dystrophy (EEM syndrome) in siblings. American Journal of Medical Genetics. 2001;101(3):195–197. doi:10.1002/ajmg.1361
VI. Balarin Silva V, Simões AM, Marques de Faria AP. EEM syndrome: report of a family and results of a ten-year follow-up. Ophthalmic Genetics. 1999;20(2):95–99. doi:10.1076/opge.20.2.95.2290
VII. Al Zubi K, Mwafi N, Alrawashdeh HM, Al Sarireh F, Somkuwar A, Abdulmannan DM. The first reported case of CDH3-related hypotrichosis with juvenile macular dystrophy from Jordan: a case report. Ophthalmic Genetics. 2022;43(3):420–424. doi:10.1080/13816810.2022.2028298