Clinical and molecular dilemmas in the diagnosis of familial epidermolysis bullosa pruriginosa

Dystrophic epidermolysis bullosa is a rare and clinically heterogeneous mechanobullous disorder. One unusual clinical variant is epidermolysis bullosa pruriginosa (EBP), in which the combination of pruritus and skin fragility can lead to hypertrophic, lichenified nodules and plaques. This form of inherited epidermolysis bullosa may not develop clinically until adult life, leading to diagnostic confusion with acquired disorders, such as nodular prurigo, lichen simplex, lichen planus, hypertrophic scarring, or dermatitis artefacta. As in all other forms of dystrophic epidermolysis bullosa, the molecular pathology involves mutations in the gene encoding the anchoring fibril protein, type VII collagen (COL7A1), but there is no clear genotype–phenotype correlation in EBP. In this report, we describe a Chinese–Singaporean family with EBP in whom an autosomal dominant glycine substitution mutation, p.G2251E, was identified in exon 86 of the COL7A1 gene. This heterozygous mutation was identified in the genomic DNA of all 4 affected adults tested, as well as 2 clinically unaffected offspring (aged 9-29 years). Based on DNA sequencing, we predict that these individuals may develop EBP later in life, although additional factors leading to disease expression may determine phenotypic expression. Nevertheless, we plan to closely monitor these potentially presymptomatic individuals for symptoms of pruritus and early signs of the genetic disorder.