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AT-A-GLANCE

AT-A-GLANCE

  • Inherited palmoplantar keratodermas (PPKs) are a heterogeneous group of genodermatoses characterized by hyperkeratosis of the palms and soles, with or without associated features. They are usually classified according to their morphology (diffuse, focal, punctate), mode of inheritance, and the presence or absence of extracutaneous features.

  • Epidermolytic PPK (EPPK) is the most common form of diffuse keratoderma. It results from heterozygous mutations in KRT9 (most cases) or KRT1 (the minority of cases) encoding keratin 9 and keratin 1, respectively. Epidermolytic hyperkeratosis is seen on histology. A similar but milder phenotype of diffuse PPK is evident in nonepidermolytic PPK (NEPPK) Unna-Thost type, caused by heterozygous mutations in KRT1.

  • Diffuse NEPPK with transgrediens may be observed in Greither syndrome and PPK Bothnia type caused by missense heterozygous mutations in KRT1 and heterozygous gain-of-function mutations in AQP5, respectively. PPK Bothnia type also manifests with a white, spongy appearance of the palms and soles upon exposure to water.

  • Mal de Meleda is a form of autosomal recessive, progressive, diffuse, mutilating PPK with transgrediens caused by biallelic mutations in SLURP1.

  • Nagashima-type PPK is the most common type of PPK in the Asian population and is characterized by diffuse, transgrediens, nonprogressive, nonmutilating PPK. The palmoplantar skin assumes a typical whitish spongy appearance after water immersion. This form of PPK is caused by biallelic mutations in SERPIN7 encoding a serine protease inhibitor.

  • Olmsted syndrome, caused by mutations in TRPV3 (autosomal dominant or autosomal recessive inheritance) or MBTPS2 (X-linked recessive inheritance), is characterized by diffuse mutilating PPK with periorificial keratotic plaques.

  • Heterozygous mutations in the gene GJB2 encoding connexin 26 result in four genodermatoses featuring PPK and hearing impairment, including Vohwinkel syndrome (mutilating honeycomb-like PPK and starfish-shaped keratotic plaques), keratosis–ichthyosis–deafness (KID) syndrome (erythrokeratoderma, grainy PPK, abnormal ectodermal features, progressive keratitis, and recurrent infections), Bart-Pumphrey syndrome (honeycomb-like PPK, knuckle pads, and leukonychia), and PPK with deafness syndrome. A form of KID syndrome associated with congenital atrichia results from mutations in GJB6 encoding Cx30.

  • Loricrin keratoderma, caused by heterozygous frameshift mutations in LOR encoding loricrin, is a variant of Vohwinkel syndrome not associated with hearing impairment but featuring generalized ichthyosis.

  • PPK with hearing impairment can also result from point mutations in the MTTS1 gene encoding a mitochondrial transfer RNA.

  • Hidrotic ectodermal dysplasia (Clouston syndrome) is a form of ectodermal dysplasia associated with diffuse PPK and nail and hair abnormalities caused by heterozygous mutations in GJB6 encoding connexin 30.

  • Huriez syndrome, an autosomal dominant inherited PPK with unknown etiology, is characterized by diffuse PPK, scleroatrophy, sclerodactyly, and occurrence of squamous cell carcinomas within atrophic skin.

  • Papillon-Lefevre syndrome is an autosomal recessive disorder caused by mutations in the gene CTSC encoding cathepsin C. It is characterized by diffuse PPK with transgrediens and severe progressive periodontitis.

  • Naxos disease (ND) and Carvajal syndrome (CS), caused by mutations in the genes JUP and DSP encoding plakoglobin and desmoplakin, respectively, are cardiocutaneous syndromes featuring PPK (diffuse in ND and striate in CS), woolly hair, and cardiomyopathy ...

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