Pachyonychia congenita. Keratin gene mutations with pleiotropic effect

Pachyonychia congenita (PC) comprises a heterogeneous group of autosomal do minantly inherited conditions showing characteristic nail thickening and as sociated signs such as palmoplantar keratoderma,follicular keratoses, and m ucosal leukokeratoses. Less frequently epidermal cysts, hairshaft abnormali ties, natal teeth and laryngeal involvement may be seen. Phenotypically and genetically two major forms of PC are recognized, pachyonychia congenita J adassohn-Lewandowsky/PC type I (Medelian inheritance in man - MIM - 167200) and pachyonychia congenita Jackson-Lawler/PC type II (MIM 167210). Both co nditions show nail deformities,focal palmoplantar keratoderma,and follicula r hyperkeratoses. Diagnostically relevant are leukokeratoses of the oral mu cosa in patients with PC type I. In contrast individuals affected with PC t ype II show premature dentition and multiple pilosebaceous cysts predominan tely affecting the upper trunk. The latter closely resemble eruptive vellus hair cysts and steatocystoma multiplex. By mutational analysis keratin K6a and K16 gene mutations have been detected in patients with PC type I, and keratin K6b and K17 gene mutations have been shown to be the underlying gen etic defect in patients with PC type II.