Pachyonychia congenita type 2 (PC-2; Jackson-Lawler syndrome) is an autosomal dominant disorder characterized by hypertrophic nail dystrophy, mild focal keratoderma, multiple pilosebaceous cysts and other features of ectodermal dysplasia. Keratin 17 (K17) is a differentiation-specific keratin expressed in the nail bed, hair follicle, sebaceous gland and other epidermal appendages. Previously, we have demonstrated that PC-2 is caused by mutations in K17 and that similar mutations in this gene can present as steatocystoma multiplex with little or no nail dystrophy. Here, we describe three unrelated kindreds carrying K17 mutations. Two of these families have identical missense mutations (R94C) in the 1A domain of K17. However, while affected members of one kindred have the classical features of PC-2, affected persons in the other family have the steatocystoma multiplex phenotype. In a third family with PC-2, mutation N92S was detected, bringing the total number of distinct mutations reported in K17 thus far to 11. These results demonstrate that K17 mutations commonly underlie both PC-2 and steatocystoma multiplex and that the alternate phenotypes which arise from these genetic lesions in K17 are independent of the specific mutation involved.

The distribution and clinical appearance of the telangiectasia in the CREST syndrome (calcinosis, Raynaud's phenomenon, oesophageal involvement, sclerodactyly, telangiectasia) and hereditary haemorrhagic telangiectasia (HHT) are very similar. Several previously reported cases of the CREST syndrome simulating HHT illustrate this diagnostic quandary. We report a patient who met the diagnostic criteria for both the CREST syndrome and HHT, and discuss the distinguishing features of the two diseases, including the distinctive histopathological findings of telangiectasia in HHT.

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