Disease characteristics
Pachyonychia congenita (PC) is characterized by hypertrophic nail dystrophy, focal palmoplantar keratoderma and blistering, oral leukokeratosis, cyst formation, palmoplantar hyperhydrosis, and follicular keratoses on the trunk and extremities. PC includes two main subtypes, pachyonychia congenita type 1 (PC-1) and pachyonychia congenita type 2 (PC-2). Variants of PC include focal non-epidermolytic palmoplantar keratoderma (FNEPPK), with keratoderma occurring on the palms and soles but usually without nail dystrophy; steatocystoma multiplex (SM) with widespread cysts but with little or no nail involvement or palmoplantar keratoderma; and late-onset PC (PC tarda), which resembles either PC-1 or PC-2 and has onset from late childhood to middle age.
Diagnosis/testing
PC is diagnosed by clinical findings and by molecular genetic testing. The two keratin genes known to be associated with PC-1 are KRT6A (encoding keratin, type II cytoskeletal 6a) and KRT16 (encoding keratin, type I cytoskeletal 16). The two keratin genes known to be associated with PC-2 are KRT6B (encoding keratin, type II cytoskeletal 6b) and KRT17 (encoding keratin, type I cytoskeletal 17). Molecular genetic testing of these four genes is available on a clinical basis.
Management
Treatment of manifestations: Pain from the palmoplantar keratoderma can be reduced by limiting friction and trauma to the feet by minimizing walking or standing, reducing hydration of the stratum corneum by using wicking socks and ventilated footwear, selecting comfortable shoes, and maintaining ideal body weight. Foot care includes paring down hyperkeratotic areas and topical therapies for hyperkeratosis including emollients and lotions containing keratolyics. Early detection permits treatment of secondary bacterial and yeast/fungal infections on the feet and nails and in the mouth. Care of thickened nails often requires the use of surgical or razor blades or sanders such as a Dremel® tool. Troublesome nails can be removed surgically. Frequent brushing of teeth can improve the appearance of thick, white patches on the tongue and oral mucosa. Poor feeding in infants with leukokeratosis may require use of a bottle with a soft nipple and an enlarged opening. Rarely, emergency surgical intervention may be needed to re-establish the airway in young children with laryngeal thickening/growths. Steatocystoma multiplex and other pilosebaceous cysts can be treated initially by incision and drainage. Prevention of secondary complications: attention to pre- and post-grooming hygiene to prevent infection. Agents/circumstances to avoid: trauma, friction, and sheer forces to the skin and nails. Therapies under investigation: Studies on the use of a K6a mutation-specific siRNA, rapamycin, anti-TNF biologics, and botulism toxin are underway.
Genetic counseling
Pachyonychia congenita is inherited in an autosomal dominant manner. Approximately 50% of cases appear to result from a de novo mutation. Offspring of an affected individual have a 50% chance of inheriting the disorder. Prenatal diagnosis is possible for pregnancies at increased risk if the disease-causing mutation in the family is known.
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