[4] Other features noted in association with EEC include vesicoureteral reflux, recurrent urinary tract infections,[5] obstruction of the nasolacrimal duct,[6] decreased pigmentation of the hair and skin, missing or abnormal teeth, enamel hypoplasia, absent punctae in the lower eyelids, photophobia, occasional cognitive impairment and kidney anomalies, and conductive hearing loss.
The ectodermal derivative abnormalities can affect the epidermis including mammary, pituitary and sweat glands, as well as hairs, dental enamel, nails, lens, and the internal ear.
[10] The hypohydrotic symptoms of ectodermal dysplasia described above are evidenced not only in the skin of affected individuals, but also in their phonation and voice production.
[11] This results in air escapement between the folds and the production of breathy voice, which often accompanies the skin abnormalities of ectodermal dysplasia.
Articulation is further impaired by the numerous dental anomalies, including missing or malformed teeth found in EEC syndrome.
Conductive hearing loss due to ossicular anomalies is often encountered in patients with EEC syndrome, which can have significant impacts on language acquisition.
In general terms, ectodermal cells generate the skin, spinal cord, and teeth (as well as the numerous derivatives mentioned above).
Epithelial-mesenchymal interactions between the apical ectodermal ridge (AER) and the underlying mesenchyme, denoted the progress zone, are required for normal morphogenesis of the limb.
[8] Genetics research relating to EEC has made great strides in recent years, but many findings are currently being debated in the literature.
This is supported by reports (though conflicting) regarding an association of cleft lip +/- palate on locus 19q, which suggests that EEC could be an allelic variant.
Brunner and colleagues found that most of the p63 mutations associated with EEC "involve amino acid substitutions in the DNA binding domain common to all known p63 isoforms".
One study found three of the five listed amino acid mutations in their subjects and noted that when 200 control chromosomes were tested, these three mutant alleles were not present.
This means that in some cases, EEC expresses de novo in a child of unaffected parents (sporadic) due to spontaneous mutation, in addition to the existing autosomal dominant inherited form.
Particularly striking are severe limb truncations with forelimbs showing a complete absence of the phalanges and carpals, and variable defects of ulnae and radiae and hindlimbs that are lacking altogether…The p63 mutations act in a dominant fashion in humans, giving rise to a phenotype that resembles that of p63 knockout mice.
[12] All of these findings are consistent with the clinical presentation of EEC in humans and may explain the association of limb malformation and clefting that are found in this syndrome.
[19] Further genetic research is necessary to identify and rule out other possible loci contributing to EEC syndrome, though it seems certain that disruption of the p63 gene is involved to some extent.