Striate palmoplantar keratoderma belongs to a group of skin diseases in which there is thickening of the skin on the palms and soles. The striate form is characterized by longitudinal hyperkeratotic lesions extending the length of each finger ... Striate palmoplantar keratoderma belongs to a group of skin diseases in which there is thickening of the skin on the palms and soles. The striate form is characterized by longitudinal hyperkeratotic lesions extending the length of each finger to the palm, and hyperkeratotic lesions are restricted to regions of the body where pressure and abrasion are greatest (summary by Hunt et al., 2001). Patients with diffuse or focal forms of keratoderma associated with mutation in the DSG1 gene have also been reported (Keren et al., 2005; Milingou et al., 2006). - Genetic Heterogeneity of Keratosis Palmoplantaris Striata Type II PPKS (PPKS2; 612908) is caused by mutation in the DSP gene (125647) on chromosome 6. Type III PPKS (PPKS3; 607654) is caused by mutation in the keratin-1 gene (KRT1; 139350) on chromosome 12q. For a general phenotypic description and a discussion of genetic heterogeneity of palmoplantar keratoderma (PPK), see epidermolytic PPK (144200).
Bergman et al. (2010) analyzed biopsies from 4 patients with DSG1 mutations, including the patient with diffuse PPK originally reported by Keren et al. (2005) and the 3 patients with PPKS previously studied by Hershkovitz et al. (2008), ... Bergman et al. (2010) analyzed biopsies from 4 patients with DSG1 mutations, including the patient with diffuse PPK originally reported by Keren et al. (2005) and the 3 patients with PPKS previously studied by Hershkovitz et al. (2008), comparing them to biopsies from 4 patients with palmoplantar keratoderma and mutations in the SLURP1 gene (606119; see Mal de Meleda, 248300), 1 patient with pachyonychia congenita type II (167210) and a mutation in KRT17 (148069), and 1 patient with focal palmoplantar keratoderma (FNEPPK; 613000) and a mutation in KRT16 (148067). The distinguishing histopathologic features of the cases with mutations in DSG1 included varying degrees of widening of the intercellular spaces and partial disadhesion of keratinocytes in the mid and upper epidermal spinous cell layers, often extending to the granular cell layer. These findings were not observed in any of the other 6 PPK cases; Bergman et al. (2010) concluded that widening of intercellular spaces and disadhesion of epidermal keratinocytes might serve as histologic clues to PPKs caused by DSG1 mutations.
The lesions of the hands consist of a streak of hyperkeratosis running the length of each finger and onto the palm. Bologna (1966) reported a 4-generation kindred in which involvement of males predominated in a striking manner. This ... The lesions of the hands consist of a streak of hyperkeratosis running the length of each finger and onto the palm. Bologna (1966) reported a 4-generation kindred in which involvement of males predominated in a striking manner. This disorder is also referred to as the Brunauer-Fohs-Siemens type of palmoplantar keratoderma. Hennies et al. (1995) described a German kindred with a striated form of palmoplantar keratoderma. Affected members of this family showed marked hyperkeratosis resembling that found in cases of epidermolytic (144200) and nonepidermolytic (600962) palmoplantar keratoderma. Keren et al. (2005) studied a 50-year-old man of Jewish Yemenite origin, who from 3 years of age had thickening of the skin of the palms and soles accompanied by painful fissures. He had 5 daughters, 3 of whom displayed a milder form of keratoderma, mainly evident on the soles. His maternal grandfather, but not his mother, was reported to have been similarly affected. On examination, he had diffuse hyperkeratosis and fissuring on the volar surface of the hands and digits and over the weight-bearing areas of the soles and toes. Mild onycholysis was also present, with yellowish discoloration of most nails. Hair, teeth, mucosae, and nonpalmoplantar skin were normal. Histologic examination of a palmar skin biopsy showed papillomatosis and marked orthohyperkeratosis in the epidermis, with widening of intercellular spaces and disadhesion of keratinocytes in the upper spinous and granular cell layers. Milingou et al. (2006) reported a father and 2 daughters from a consanguineous Libyan family with a focal, nonstriated form of palmoplantar keratoderma. The proband was a 12-year-old girl who had progressive thickening of her soles from 5 years of age. Examination revealed thick, yellow, and fissured focal areas of keratosis on sites of pressure of the soles and toes. Her toenails were relatively small, slightly ridged, and partially white. Her palms also showed focal areas of slight keratosis on pressure sites. There were slightly hyperkeratotic plaques with follicular keratoses on her knees and on the anterolateral aspect of her ankles. Smooth circumscribed keratoses were observed over the dorsa of some proximal and distal interphalangeal joints of her fingers and toes. The angles of her mouth also showed slight hyperkeratosis. Her 39-year-old father and 6-year-old sister had similar but less pronounced hyperkeratotic lesions on pressure points of the soles, whereas the remainder of the physical examination was unremarkable. Light microscopy of a plantar skin biopsy from the proband showed marked hyperkeratosis, acanthosis, and papillomatosis; there were no epidermolytic changes. Hershkovitz et al. (2008) studied 3 families with striate palmoplantar keratoderma, including 1 of Jewish Sephardic descent and 2 of Jewish Ashkenazi origin. All 9 patients displayed focal areas of hyperkeratosis, involving palms, soles, and the palmar surface of the fingers. Marked intrafamilial variation was noted. In all cases, histologic examination of palmoplantar skin biopsies revealed orthohyperkeratosis, papillomatosis, widening of the intercellular spaces, and separation of keratinocytes in the upper spinous and granular cell layers. Dua-Awereh et al. (2009) analyzed 5 Pakistani families segregating autosomal dominant PPKS. All affected individuals had hyperkeratosis of the palms, predominantly on the creases, with linear hyperkeratosis along the flexor aspects of the fingers. Focal hyperkeratosis was seen on the plantar surface of the toes as well as the balls and heels of the feet. The phenotype was more pronounced in areas that undergo frequent mechanical stress. None of the affected individuals had wooly hair, and none of the families had a history of cardiomyopathy, early sudden death, or cancer. Zamiri et al. (2009) studied a 3-generation Scottish family with the striate form of palmoplantar keratoderma. The proband was a 40-year-old man who had painful thickening of the skin on the palms and soles as well as hyperhidrosis and intermittent associated blistering since childhood. Examination showed linear hyperkeratosis of the volar aspect of the fingers, more extensive focal plantar hyperkeratosis, and mild hyperkeratosis of the knees. His father, paternal uncle, and 8-year-old daughter were similarly affected. Light microscopy of the affected plantar epidermis showed acanthosis with mild spongiosis and intracellular vacuolation, thickened granular layer with hyperkeratosis, mild upper dermal perivascular chronic inflammatory cell infiltrate, and suprabasal cell-cell separation. Electron microscopy revealed normal keratin intermediate filaments but separation of keratinocytes in the spinous layer.
In a Dutch family with striate palmoplantar keratoderma, Rickman et al. (1999) identified a heterozygous splicing mutation in the gene encoding desmoglein (125670.0001).
In 5 unrelated patients with PPKS, including an affected member of the German ... In a Dutch family with striate palmoplantar keratoderma, Rickman et al. (1999) identified a heterozygous splicing mutation in the gene encoding desmoglein (125670.0001). In 5 unrelated patients with PPKS, including an affected member of the German kindred originally studied by Hennies et al. (1995), Hunt et al. (2001) analyzed the DSG1 gene and identified heterozygous truncating mutations in all of them (see, e.g., 125670.0002-125670.0004). The preponderance of PPKS mutations in the DSG1 gene rather than in another desmosomal cadherin suggested that desmoglein-1 is a key protein in desmosome structure and function in the epidermis, and that PPKS provides a very sensitive measure of correct desmosome function. In a family of Jewish Yemenite origin with autosomal dominant diffuse PPK mapping to 18q12, Keren et al. (2005) analyzed the DSG1 gene and identified a heterozygous nonsense mutation (R26X; 125670.0004) that segregated completely with the disease. The same mutation had previously been detected in a sporadic patient with striate PPK (Hunt et al., 2001). In a father and 2 daughters with a focal, nonstriated form of palmoplantar keratoderma from a consanguineous Libyan family, Milingou et al. (2006) identified heterozygosity for a frameshift mutation in the DSG1 gene (125670.0005) that was not found in unaffected family members or in 50 unrelated controls. The authors noted that the phenotype in this family extended the spectrum of clinical features associated with genetic defects in DSG1. Hershkovitz et al. (2008) sequenced the DSG1 gene in 3 families with PPKS, including 1 of Jewish Sephardic descent and 2 of Jewish Ashkenazi origin, and identified 3 different heterozygous truncating mutations (see, e.g., 125670.0006) that segregated with disease in each family, respectively. Direct sequencing of cDNA derived from affected skin failed to reveal a pathogenic mutation, suggesting that PPKS results from haploinsufficiency for DSG1.