Diffuse and focal palmoplantar keratoderma can be caused by a keratin 6c mutation

Abstract

The palmoplantar keratodermas (PPKs) are a large group of genodermatoses comprising nearly 60 genetically distinct diseases. They are characterized by hyperkeratosis on the palms and soles with or without extrapalmoplantar hyperkeratotic lesions. Focal PPK is one of the hallmarks of pachyonychia congenita, a rare autosomal dominant disorder resulting from mutations in the keratin genes KRT6A, KRT6B, KRT16 or KRT17. Recently, in-frame deletion mutations of KRT6C have been identified in three families with focal PPK with slight or no nail changes. We report here a novel KRT6C mutation identified in a Japanese family with PPK with phenotypic heterogeneity, presenting with not only focal but also diffuse hyperkeratosis. The proband had diffuse hyperkeratosis on the soles and small focal hyperkeratoses on the palms, while the two other affected individuals showed focal hyperkeratoses on the soles. All three patients were heterozygotes for c.1414G>A in KRT6C, predicted to result in p.Glu472Lys. These findings strongly suggest that screening of patients with nonepidermolytic diffuse PPK, in whom the pathogenic mutations are yet to be determined, might identify mutations in KRT6C.

Focal PPK secondary to a novel KRT6C mutation (Pachyonychia congenita‐K6c)

“…This new efficacy parameter assesses the ability of field-directed AK therapies to detect and clear clinical lesions and subclinical lesions which become detectable during treatment. 2 Treatment with imiquimod 3.75% was not interrupted in 143 (89%) patients, while 17 (11%) took a rest period. The median number of dosing days missed due to rest periods was five (range: 1-20).…”

“…There have been just a few reports of KRT6C mutations, which manifests as a painful focal PPK with absent or mild toenail dystrophy. [1][2][3][4][5] Other features of PC appear to be rarely seen with KRT6C mutations, with steatocystoma and oral leucokeratosis reported in one family. 4 We report on a patient with focal nonepidermolytic PPK secondary to a novel KRT6C mutation.…”

Hereditary palmoplantar keratodermas. Part I. Non‐syndromic palmoplantar keratodermas: classification, clinical and genetic features

“…Autosomal dominant mutations of KRT6C and KRT16 (Table ), encoding the site‐specific keratins 6c (K6c) and 16 (K16) (Table ), cause focal PPK usually with prominent friction‐related patchy hyperkeratosis on soles and limited or even absent palm involvement (Table ). Histopathological features are hypergranulosis, acanthosis and hyperkeratosis without epidermolytic changes .…”

“…Rarely, minimal nail changes (onychocorneal bands, hypertrophy of the fifth toenail, splinter haemorrhages) and oral leukokeratosis may also occur. PPKs due to KRT6C mutations may diffusely affect the soles in individuals with high occupational mechanical stress, a fact that highlights the role of environmental factors in modulating disease phenotypic expression. Of note, mutations in KRT6A , KRT6B , KRT6C , KRT16 and KRT17 cause pachyonychia congenita, a group of autosomal dominant disorders of keratinization, characterized by PPK, severe nail dystrophy, oral leukokeratosis, pilosebaceous cysts, steatocystoma and natal teeth (i.e.…”

Pachyonychia Congenita Project

“…Under the calluses are extremely painful blisters on the soles and sometimes on the palms. PC is caused by a single mutation in one of at least five keratin genes, KRT6A, KRT6B, KRT6C, KRT16, or KRT17 (Akasaka et al, 2011;Wilson et al, 2010Wilson et al, , 2011. PC is caused by a single mutation in one of at least five keratin genes, KRT6A, KRT6B, KRT6C, KRT16, or KRT17 (Akasaka et al, 2011;Wilson et al, 2010Wilson et al, , 2011.…”