Pachyonychia Congenita 2

A number sign (#) is used with this entry because of evidence that pachyonychia congenita-2 (PC2) is caused by heterozygous mutation in the KRT17 gene (148069) on chromosome 17q21.


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 KRT17 gene, here designated PC2, has also been designated PC-17 (Eliason et al., 2012) and PC-K17 (Shah et al., 2014).

Clinical Features

Jackson and Lawler (1951-52) reported 6 affected members of 3 generations of a family with pachyonychia congenita. In 4 generations of a family, Vineyard and Scott (1961) observed steatocystoma associated with pachyonychia congenita. Hodes and Norins (1977) reported the same association. Soderqvist and Reed (1968) described the same association but thought that the cysts were epidermal cysts. They presented an interesting, illustrated newspaper clipping that described neonatal teeth in persons of 3 generations. The adult teeth were sound.

Clementi et al. (1986) described a family in which 3 members in 2 generations had pachyonychia congenita, hyperkeratosis, and hyperhidrosis of the palms and soles, follicular keratosis, neonatal teeth, and epidermoid cysts. They pointed out that this is the rarer form of pachyonychia congenita. Armpit folliculitis was described in the 21-year-old proposita and in her 61-year-old mother. Cysts in the metacarpal and elbow regions were observed at puberty in the daughter. They were noted to adhere to the overlying skin on the elbows, dorsal surface of the proximal phalanges, and on the knees and pretibial regions.


In a large kindred extensively affected with pachyonychia congenita of the Jackson-Lawler type, Munro et al. (1994) found tight linkage of the disease locus to markers mapping within, or very close to, the keratin type I cluster at 17q12-q21. Maximum lod scores for linkage of the disease to a KRT10 (148080) polymorphism and to D17S800, a marker known to be very tightly linked to KRT10, were, respectively, 4.51 and 7.73, both at theta = 0.00. The findings suggested a role for keratins in the phenomenon of natal dentition.

Molecular Genetics

In the kindred with pachyonychia congenita of the Jackson-Lawler type studied by Munro et al. (1994), McLean et al. (1995) showed that a heterozygous asn92-to-asp mutation (148069.0001) in the helix initiation motif of keratin-17 cosegregated with the disease.

Terrinoni et al. (2001) studied 13 patients with pachyonychia congenita and found mutations in K6A (148041), K16 (148067), or K17 in all cases. They concluded that K6A or K16 mutations produce the Jadassohn-Lewandowsky phenotype, whereas K17 or K6B (148042) mutations produce the Jackson-Lawler phenotype.