EEC syndrome, Arg227Gln TP63 mutation and micturition difficulties: Is there a genotype–phenotype correlation?

Abstract

We report on two unrelated families with EEC syndrome (ectrodactyly, ectodermal dysplasia, cleft lip/palate), each with an Arg227Gln TP63 gene mutation, where the phenotype overlapped extensively with the allelic disorder, limb-mammary syndrome (LMS). Features common to both families were an ectodermal dysplasia principally affecting tooth, breast and nipple development, dacryostenosis and severe micturition difficulties. Additional findings included post-axial digital hypoplasia, cleft uvula, anal stenosis, hypoplasia of the perineal body and biopsy-proven interstitial cystitis. No individual had cleft lip. Split hand-split foot malformation (SHFM) occurred in one child-born after the molecular diagnosis was established. Unlike previous reports, the urinary symptoms were refractory to treatment with oral Fibrase and persisted into adulthood. Of the six cases/families now reported with EEC syndrome and Arg227Gln TP63 mutation, four have manifested this distinct urological abnormality, indicative of a genotype-phenotype correlation.