The past decade has witnessed an expansion of molecular approaches facilitating the differential diagnosis of
ectodermal dysplasias, a group of
genetic diseases characterized by the lack or malformation of hair, teeth, nails, and certain eccrine glands. Moreover, advances in translational research have increased the therapeutic opportunities for such
rare diseases, and new dental, surgical, and ophthalmic treatment options are likely to offer relief to many individuals affected by
ectodermal dysplasias. In X-linked
hypohidrotic ectodermal dysplasia (XLHED), the genetic deficiency of the signaling molecule
ectodysplasin A1 (EDA1) may even be overcome before birth by administration of a recombinant replacement
protein. This has been shown at least for the key problem of male subjects with XLHED, the nearly complete absence of sweat glands and perspiration which can lead to life-threatening
hyperthermia. Prenatal treatment of six boys by injection of an EDA1 replacement
protein into the amniotic fluid consistently induced the development of functional sweat glands. Normal ability to sweat has so far persisted for >5 years in the two oldest boys treated in utero. Thus, timely replacement of a missing
protein appears to be a promising therapeutic strategy for the most frequent
ectodermal dysplasia and possibly additional
congenital disorders.