Epidermolytic palmoplantar keratoderma-1 (EPPK1) is an autosomal dominant skin disorder characterized clinically by diffuse, yellow thickening of the skin of the palms and soles. There is no extension of the keratoderma to dorsal surfaces of hands and feet, inner wrists, and Achilles tendon area (transgrediens). Knuckle pads may be present in some individuals (summary by Kuster et al., 2002, Chiu et al., 2007). Genetic Heterogeneity of Epidermolytic Palmoplantar Keratoderma Epidermolytic palmoplantar keratoderma-2 (EPPK2; 620411) is caused by mutation in the keratin-1 gene (KRT1; 139350) on chromosome 12q13. Classification of Palmoplantar Keratoderma PPK has been classified into diffuse, focal, and punctate forms according to the pattern of hyperkeratosis on the palms and soles (Lucker et al., 1994). Diffuse PPK develops at birth or shortly thereafter and involves the entire palm and sole with a sharp cutoff at an erythematous border; there are no lesions outside the volar skin, and, in particular, no follicular or oral lesions. In contrast, focal PPK is a late-onset form in which focal hyperkeratotic lesions develop in response to mechanical trauma; an important distinguishing feature is the presence of lesions at other body sites, e.g., oral and follicular hyperkeratosis (Stevens et al., 1996). Palmoplantar keratodermas can be further subdivided histologically into epidermolytic and nonepidermolytic PPK (Risk et al., 1994). Genetic Heterogeneity of Palmoplantar Keratoderma Nonepidermolytic palmoplantar keratoderma (NEPPK; 600962) is caused by mutation in the KRT1 gene. A focal form of NEPPK (FNEPPK1; 613000) is caused by mutation in the KRT16 gene (148067). Another focal form, FNEPPK2 (616400), is caused by mutation in the TRPV3 gene (607066); mutation in TRPV3 can also cause Olmsted syndrome (OLMS; 614594), a severe mutilating form of PPK. The diffuse Bothnian form of NEPPK (PPKB; 600231) is caused by mutation in the AQP5 gene (600442). The Nagashima type of nonepidermolytic diffuse PPK (PPKN; 615598) is caused by mutation in the SERPINB7 gene (603357). A generalized form of epidermolytic hyperkeratosis (EHK; 113800), also designated bullous congenital ichthyosiform erythroderma (BCIE), is caused by mutation in the keratin genes KRT1 and KRT10 (148080). For a discussion of punctate PPK, see 148600; for a discussion of striate PPK, see 148700. [from OMIM]

Classic Vohwinkel syndrome is characterized by papular and honeycomb keratoderma associated with constrictions of digits leading to autoamputation, distinctive starfish-like acral keratoses, and moderate degrees of sensorineural deafness (summary by Maestrini et al., 1999) A variant form of Vohwinkel syndrome, mutilating keratoderma with ichthyosis (604117), is caused by mutation in the gene for loricrin (LOR; 152445) on chromosome 1q21. A form of mutilating palmoplantar keratoderma with periorificial keratotic plaques (Olmsted syndrome; 614594) is caused by mutation in the TRPV3 gene (607066) on chromosome 17p13.2. [from OMIM]

X-linked Olmsted syndrome (OLMSX) is a rare keratinization disorder characterized by the combination of periorificial keratotic plaques and bilateral palmoplantar transgredient keratoderma. Other clinical manifestations include diffuse alopecia, leukokeratosis of the oral mucosa, onychodystrophy, hyperkeratotic linear streaks, follicular keratosis, and constriction of the digits (summary by Yaghoobi et al., 2007). For a general phenotypic description and a discussion of genetic heterogeneity of Olmsted disease, see OLMS1 (614594). [from OMIM]

Olmsted syndrome-2 (OLMS2) is characterized by mutilating hyperkeratotic skin lesions, primarily on the palms and soles, but also extending onto dorsal surfaces of the hands and feet and distal extremities. The lesions are progressive, becoming thicker with verrucous fissures on the palms and soles over time. In addition, affected individuals exhibit perioral hyperkeratosis, and may have lesions around other orifices as well, such as the nostrils, perineum, and anus. Most patients also have hyperkeratotic nails and light-colored woolly hair (Duchatelet et al., 2019). Some patients may experience flexion contractures of the digits due to the severity of the keratoderma, and intractable pruritus and alopecia universalis have been observed (Dai et al., 2020). For a general phenotypic description and discussion of genetic heterogeneity of Olmsted disease, see OLMS1 (614594). [from OMIM]

Olmsted syndrome-1 (OLMS1) is a rare congenital disorder characterized by bilateral mutilating palmoplantar keratoderma (PPK) and periorificial keratotic plaques with severe pruritus of lesions. Diffuse alopecia, constriction of digits, and onychodystrophy have also been reported. Infections and squamous cell carcinomas can arise on the keratotic areas (summary by Lin et al., 2012). The digital constriction ('pseudoainhum') may progress to autoamputation of fingers and toes (Olmsted, 1927). Genetic Heterogeneity of Olmsted Syndrome Olmsted syndrome-2 (OLMS2; 619208) is caused by mutation in the PERP gene (609301) on chromosome 6q23. An X-linked form of Olmsted syndrome (OLMSX; 300918) is caused by mutation in the MBTPS2 gene (300294) on chromosome Xp22. [from OMIM]