Pachyonychia Congenita 3

A number sign (#) is used with this entry because pachyonychia congenita-3 (PC3) is caused by heterozygous mutation in the keratin-6a gene (KRT6A; 148041) on chromosome 12q13.


Pachyonychia congenita (PC) is an autosomal dominant genodermatosis with the main clinical features of hypertrophic nail dystrophy, painful and highly debilitating plantar keratoderma, oral leukokeratosis, and a variety of epidermal cysts. Although the condition had previously been subdivided clinically into Jadassohn-Lewandowsky PC type 1 and Jackson-Lawler PC type 2, patients with PC were later found to have a mixed constellation of both types, leading to a classification of PC based on genotype (summary by Sybert, 2010; Eliason et al., 2012; McLean et al., 2011).

For a discussion of genetic heterogeneity of pachyonychia congenita, see 167200.

Historical Classification of Pachyonychia Congenita

Gorlin et al. (1976) suggested that 2 distinct syndromes are subsumed under the designation pachyonychia congenita. PC type 1, the Jadassohn-Lewandowsky type, shows oral leukokeratosis. PC type 2, the Jackson-Lawler type, has natal teeth and epidermoid cysts (cylindromas), but no oral leukoplakia. Corneal dystrophy may be a feature exclusively of the Jackson-Lawler type.

Smith et al. (1998) stated that PC type 2, in contrast to PC type 1, has minimal oral involvement and milder keratoderma, and multiple steatocystomas (184500) is a major clinical feature. Steatocystoma, also known as eruptive vellus cyst, is a cystic hamartoma lined by sebaceous ductal epithelium.

On the basis of a study of 13 patients with PC type 1 or type 2, Terrinoni et al. (2001) concluded that the presence of pilosebaceous cysts following puberty is the best indicator of PC type 2; prepubescent patients are more difficult to classify due to the lack of cysts. Natal teeth are indicative of PC type 2, although their absence does not preclude the PC type 2 diagnosis.


The form of PC caused by mutation in the KRT6A gene, here designated PC3, has also been designated PC-6a (Eliason et al., 2012) and PC-K6a (Shah et al., 2014).

Clinical Features

Bowden et al. (1995) identified a Slovenian family in which a grandfather, father, and daughter had pachyonychia congenita of the Jadassohn-Lewandowsky type. The father and daughter had classic changes with thickened nails, palmoplantar keratoderma, and leukokeratosis of the tongue. The grandfather had only minor nail changes and mild keratoderma.

Du et al. (2012) reported a 32-year-old Chinese woman with toenail thickening, plantar hyperkeratosis with fissuring, and mild focal palmar hyperkeratosis but no fingernail changes. She also exhibited oral leukokeratosis, chapped lips, and fissured tongue. Histopathology of the plantar lesion showed hyperkeratosis, acanthosis, and a moderate increase in the granular layer with minimal lymphocytic infiltrate in the upper dermis. Her 7-year-old daughter had focal plantar hyperkeratosis, fissured tongue, and gingivitis, but no nail or hand involvement. Both patients reported hyperhidrosis of the hands and feet.

Molecular Genetics

In affected members of a Slovenian family segregating PC3, Bowden et al. (1995) identified heterozygosity for a 3-bp deletion in the KRT6A gene (148041.0001).

Terrinoni et al. (2001) identified 3 novel mutations (148041.0002-148041.0004) and 2 previously identified mutations (see, e.g., 148041.0001) in the KRT6A gene in patients with pachyonychia congenita.

Smith et al. (2005) identified keratin mutations in 30 probands from the International Pachyonychia Congenita Research Registry, 17 of whom had mutations in the KRT6A gene (see, e.g., 148041.0001 and 148041.0005-148041.0008).

In a 32-year-old Chinese woman with pachyonychia congenita, Du et al. (2012) identified heterozygosity for a splice site mutation in the KRT6A gene (148041.0009). Her 7-year-old daughter, who had only focal plantar hyperkeratosis with no nail or hand involvement, was also heterozygous for the mutation.