Ectodermal Dysplasia, Ectrodactyly, And Macular Dystrophy Syndrome

A number sign (#) is used with this entry because of evidence that EEM syndrome (EEMS) is caused by homozygous mutation in the CDH3 gene (114021) on chromosome 16q22.

Clinical Features

In an isolated population on a remote island in Japan, Ohdo et al. (1983) observed a kindred with 6 cases of ectodermal dysplasia, ectrodactyly associated with syndactyly or cleft hand or both, and macular dystrophy which was presumed to be progressive. Because of the parental consanguinity and the occurrence in both sexes, autosomal recessive inheritance was suggested. The presence of macular dystrophy distinguishes it from other syndromes of ectodermal dysplasia and limb malformations. The same disorder was probably reported by Albrectsen and Svendsen (1956) in the son and daughter of first-cousin parents and by Hayakawa et al. (1979) in a 30-year-old woman whose parents were first cousins. Kuster et al. (1987) considered the disorder in the single affected case they described to be distinct.

Balarin Silva et al. (1999) reported a Brazilian kindred in which 2 sibs exhibited the complete form of EEM, with hypotrichosis, dental anomalies, syndactyly, and retinal changes with prominent pigmentation in the posterior pole of the retina. Another sib exhibited minimal symptoms, consisting of mild bilateral syndactyly between fingers 1, 2, 3, and 4 and small, widely spaced teeth, whereas his ophthalmologic and hair examination were unremarkable. A first cousin also had ectrodactyly of the right hand (lobster-claw deformity) but no dental, dermatologic, or ocular abnormalities. Balarin Silva et al. (1999) followed the sibs with EEM for 10 years, observing gradually decreasing visual acuity and progression of retinal degenerative anomalies.

Senecky et al. (2001) described a brother and sister with ectodermal dysplasia, ectrodactyly, and macular dystrophy. Both children had abnormalities of the hands and the hair as well as bilateral macular degeneration. The clinical picture in both was similar to, but milder than, that described in the previously reported cases of EEMS. The parents were not related, but were of Jewish Yemenite origin.

Molecular Genetics

In affected individuals with EEMS from the Danish family reported by Albrectsen and Svendsen (1956) and from the Brazilian family reported by Balarin Silva et al. (1999), Kjaer et al. (2005) identified homozygosity for mutations in CDH3: a missense mutation (114021.0003) and a deletion (114021.0004), respectively. The minimally symptomatic brother of the proband in the Brazilian family was found to be heterozygous for the deletion mutation.