Further delineation of the hypotrichosis-deafness syndrome

We recently delineated a novel disorder characterized by hypotrichosis, nail dystrophy and sensorineural deafness and caused by a missense mutation in GJB2 (connexin26). The patient, a girl, was two years old when we first saw her. We had the opportunity to re-examine her at four years of age and found that the phenotype had changed appreciably. The hypotrichosis was less pronounced, but the nail dystrophy had worsened. Intriguingly, the phenotype now included a mucositis and skin lesions identical to those found in erythrokeratodermia variabilis. There is now a considerable overlap with other gap junction disorders and we propose that some cases of erythrokeratodermia variabilis without mutations in either GJB3 or GJB4 but with deafness may be caused by mutations in GJB2. This is the first description of the evolution of a gap junction disease over time and we note that follow-up of patients suffering from gap junction skin disorders is necessary to fully delineate the phenotypes caused by mutations in gap junction genes.