Pachyonychia Congenita With Recessive Inheritance

We report the second and third cases of pachyonychia congenita inherited as an autosomal recessive disorder. Our cases were unusual, with the fingernails showing a striking leukonychia and appearing clinically as Terry's nails. These patients were originally diagnosed as having epidermolysis bullosa simplex because of a history of a life-long blistering disorder. The clinical features and inheritance of pachyonychia congenita, as well as the reasons for the long delay in diagnosis of our cases, are discussed.

Autosomal Recessive Pachyonychia Congenita

Haber¹,

Rose²

1986

Pachyonychia Congenita Tarda

Paller¹

1991

Pachyonychia congenita is an autosomal dominant disorder that usually develops in early infancy. We have observed five patients with the onset of the typical subungual hyperkeratoses of pachyonychia during the teenage years. Leukokeratosis and keratoderma of the palms and soles were associated. The family history of three of the patients suggests that pachyonychia congenita tarda is also inherited in an autosomal dominant manner.

Paternal Germ Cell Mosaicism in Autosomal Dominant Pachyonychia Congenita

Pho

Smith

Konecki³

et al. 2011

Background: Pachyonychia congenita (PC) is a genodermatosis caused by mutations in 1 of 4 known keratin genes, including KRT6A, KRT6B, KRT16, or KRT17. The most common mode of inheritance is autosomal dominant. Families with an affected parent are routinely counseled about the 50% transmission risk to each offspring. In some cases, families with a rare disorder like PC can initially present with an affected child while both parents are unaffected. This is usually the result of a spontaneous in utero mutation, and the risk of subsequent offspring being affected with the same condition is negligible (but may be increased above the general population's risk, although the exact risk is not currently known for PC). Observations: We discuss a case of 2 affected children born to unaffected parents. We performed muta-tional analyses of all 4 individuals in the family on DNA extracted from lymphocytes. Owing to the unusual presentation of 2 affected siblings, we also extracted DNA from the father's sperm cells for keratin gene mutational analysis. We describe the first case, to our knowledge, of germ cell mosaicism in PC. Conclusion: Counseling of unaffected parents with a first child diagnosed as having PC should entail a discussion of the possibility of germ cell mosaicism contributing to an increased risk of having subsequent affected children.