The three cardinal signs of the syndrome are ectrodactyly and syndactyly of the hands and feet, cleft lip with or without cleft palate (that can result in speech defects), and abnormalities in several ectodermal structures including skin (i.e. hypopigmentated and dry skin, hyperkeratosis, skin atrophy), hair (i.e. fine and sparse hair and eyebrows), teeth (small, absent or dysplastic teeth), nails (nail dystrophy) and exocrine glands (reduction/absence of sweat, sebaceous and salivary glands).
In more than 90% of cases, EEC is due to missense mutations in the sequence of the TP63 gene (3q27) encoding the TP63 transcription factor that is essential for ectoderm and limb development. These cases correspond to the classical EEC syndrome (EEC type 3) and seem to present some degree of genotype-phenotype correlation. The other cases correspond to EEC syndrome type 1, which shows associated clinical features such as malformedauricles and middle and inner ear malformations, and was mapped to 7q21. EEC type 2 does not exist anymore. EEC syndrome is an autosomal dominant disorder with incomplete penetrance (between 93 and 98%) and variable expression.
