Pachyonychia congenita und Steatocystoma multiplex durch Mutation im Keratin-17-Gen

Zusammenfassung

Die Pachyonychia congenita (PC) wird durch heterozygote Mutationen in den Keratin-Genen KRT6A, KRT6B, KRT6C, KRT16 oder KRT17 verursacht. Die Einteilung in PC Typ 1 und PC Typ 2 nach klinischen Kriterien wurde zugunsten einer molekulargenetischen Klassifikation auf Basis der 5 betroffenen Gene (PC-K6a, PC-K6b, PC-K6c, PC-K16, PC-K17) verlassen. Die Erkrankung wird autosomal-dominant vererbt, Spontanmutationen kommen in etwa 30 % der Fälle vor. Über 97 % der PC-Patienten weisen die 3 Hauptsymptome Verdickung der Fußnägel, Plantarkeratosen und Fußsohlenschmerzen auf.

Lokalisierte Steatozystome, Vellushaarzysten oder das diffuse Steatocystoma multiplex zeichnen die PC durch Keratin-17-Mutationen aus. Konnatale oder perinatale Zähne und follikuläre Hyperkeratosen an Ellenbogen, Knien und Rumpf sind ebenfalls häufig mit einer Mutation in KRT17 vergesellschaftet. Wir berichten über eine 40-jährige Patientin mit Steatocystoma multiplex, Verdickung und distaler Dystrophie aller Nägel, schmerzhaften Plantarkeratosen und palmoplantarer Hyperhidrose. Molekulargenetisch konnte mittels Next-Generation-Sequencing eine Mutation im Exon 1 des KRT17-Gens als ursächlich nachgewiesen werden.

Abstract

Pachyonychia congenita (PC) is caused by heterozygous mutations in the keratin genes KRT6A, KRT6B, KRT6C, KRT16 or KRT17. The historical distinction of PC type 1 and PC type 2 based on clinical findings was left in favor of the recent classification according to the mutated gene (PC-K6a, PC-K6b, PC-K6c, PC-K16, PC-K17). The genodermatosis is transmitted in an autosomal dominant mode of inheritance, spontaneous mutations are responsible for about 30 % of cases. More than 97 % of affected patients suffer from the typical triad of nail hypertrophy, plantar keratoderma und plantar pain.

Localized pilosebaceous cysts, vellus hair cysts or widespread steatocystoma multiplex are typical findings in PC due to mutations in the keratin 17 gene. Further findings include natal or perinatal teeth and follicular keratoses on trunk, elbows and knees. We report a 40-year-old female presenting with steatocystoma multiplex, thickening and distal dystrophy of all nails, painful plantar keratoses and palmoplantar hyperhidrosis. Mutation analysis by next-generation sequencing revealed a causative mutation in exon 1 of the KRT17 gene.

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