CDH3 – Ectodermal Dysplasia, Ectrodactyly and Macular Dystrophy (EEM) Syndrome

CDH3 encodes P-cadherin and is implicated in autosomal recessive EEM syndrome, characterized by ectodermal dysplasia (HP:0000968), ectrodactyly (HP:0100257), and macular dystrophy (HP:0007754). Molecular analysis in 2 unrelated families (PMID:15805154) identified homozygous CDH3 mutations: a missense variant c.965A>T (p.Asn322Ile) disrupting Ca²⁺ binding in cadherin repeat 3, and a frameshift c.829delG (p.Gly277AlafsTer20) predicted to truncate the protein and abolish extracellular repeats. No additional segregation beyond affected individuals was reported, consistent with autosomal recessive inheritance.

Mouse in situ hybridization demonstrates Cdh3 expression in the apical ectodermal ridge from embryonic day 10.5 to 12.5 and later in interdigital mesenchyme, aligning with the limb and ectodermal defects of EEM (PMID:15805154). This supports a loss-of-function mechanism via impaired cell–cell adhesion during development. No conflicting evidence has been described. CDH3 screening should be considered in patients presenting with ectrodactyly and ectodermal dysplasia to inform diagnosis and genetic counselling.

References

• Journal of medical genetics • 2005 • Distinct CDH3 mutations cause ectodermal dysplasia, ectrodactyly, macular dystrophy (EEM syndrome). PMID:15805154

Evidence Based Scoring (AI generated)