Clinical Guidance

In all types of pachyonychia congenita (PC) most characteristics are visible by age ten years and typically include toenail thickening, plantar keratoderma, and plantar pain . However, the absence or presence of certain features as well as the age at onset varies according the gene that is mutated (see for phenotypic features of PC). The most recent classification of the condition also incorporates the genetic cause . The severity of findings can differ both within a family and among families with the same pathogenic variant.

Table 2.

International Pachyonychia Congenita Research Registry (IPCRR) Data Summary (as of 10 May 2017)

Gene in Which PathogenicVariants Were Confirmed | KRT6A | KRT6B | KRT6C | KRT16 | KRT17 | TOTAL

Number evaluated for finding1

| 304 | 71 | 22 | 247 | 130 | 774

Source: GeneReviews — "Pachyonychia Congenita"

Differential Diagnosis

Onychomycosis. While the hyperkeratotic nail thickening seen in pachyonychia congenita (PC) may be mistaken for onychomycosis, dermatophytic infections do not affect all finger and toenails, particularly at an early age. In the rare conditions of autoimmune endocrinopathy-candidiasis-ectodermal dystrophy (APECED) and systemic mucocutaneous candidosis, all nails may be affected. Oral leukokeratosis together with nail dystrophy is often an indication of pachyonychia congenita and may be mistaken for Candida albicans (thrush), white sponge nevus, and/or leukoplakia. Epidermolysis bullosa simplex (EBS) or other palmoplantar keratodermas can result in a similar pattern of plantar blister formation or hyperkeratosis, respectively; however, they do not share the characteristic nail changes of PC.

Source: GeneReviews — "Pachyonychia Congenita"

Clinical Guidance

Some report that higher temperatures and higher humidity worsen the condition.

Source: GeneReviews — "Pachyonychia Congenita"

Therapies Under Investigation

In 2014, a Phase 1b clinical trial sponsored by PC Project and TransDerm was performed using topical sirolimus. This study included 15 affected individuals and was conducted by Dr Joyce Teng at Stanford University. Background research for this trial was previously published . Short interfering RNA (siRNA) can selectively block expression of a specific K6a-causing pathogenic variant . The siRNA trial included treatment of a single individual with a specific KRT6A pathogenic variant in a dose-escalation trial of an siRNA directed against the p.Asn171Lys mutated allele . The affected individual did not experience any adverse effects from the experimental treatment. The affected person also experienced callus regression on the foot treated with siRNA.

Source: GeneReviews — "Pachyonychia Congenita"