Dowling-Degos Disease 4

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Retrieved

2019-09-22

Source

Omim

Trials

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Genes

KRT5, POFUT1, POGLUT1, PSENEN, ADAM10, CFH, IL1B, TYRP1, ACAN, CFHR5, TNF, TRP-AGG2-6, RANBP2, DCT, TBPL1, TRPV1, SHBG, LZTR1, TRPC6, SIRT1, TRPC3, TRP-TGG3-1, SMC1A, SYNGAP1, TGFBR2, TGFB1, TAC1, SPTBN2, FTO, OPA1, SET, EGF, ANG, SERPINA6, COL9A2, COL9A3, COMT, CSF1, CCN2, CTNNB1, DDT, EGR3, PTH1R, HNRNPA1, IGF1, IL4, IL5, IL6, CXCL8, LEP, LTA, NFKB1, DDTL

Drugs

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A number sign (#) is used with this entry because of evidence that Dowling-Degos disease-4 is caused by heterozygous mutation in the POGLUT1 gene (615618) on chromosome 3q13.

For a general phenotypic description and discussion of genetic heterogeneity of Dowling-Degos disease, see DDD1 (179850).

Clinical Features

Hanneken et al. (2011) studied 18 patients with Dowling-Degos disease, including 4 members of a 3-generation pedigree, 5 patients with an affected first-degree relative, and 9 sporadic patients. Onset of symptoms ranged between 15 and 53 years. Pruritus was reported in 15 patients, and was severe in 7 of them. Most patients had a chronic course with exacerbations that were triggered by heat, sweating, UV exposure, or mechanical factors such as wearing tight clothing, and about half of patients experienced significant erosions and weeping in affected areas. On examination, all patients had a symmetric distribution of skin lesions, which in 12 patients primarily involved flexural surfaces and skin folds, with reticular pigmentation in combination with reddish-brown papules that were partly erosive and partly hyperkeratotic. The remaining 6 patients exhibited a more disseminated distribution with brownish macular and lentiginous lesions involving the entire body. In addition, 3 patients displayed nearly complete involvement of the face. All patients exhibited truncal lesions, and in 12 the legs were affected.

In histologic analysis of skin lesions from individuals with mutations in the POGLUT1 gene (see MOLECULAR GENETICS), Basmanav et al. (2014) observed digitiform acanthosis of the rete ridges with pronounced hyperpigmentation at the tips, some small horn cysts, minor acantholysis, and focal hypergranulosis.

Molecular Genetics

In 5 unrelated patients with Dowling-Degos disease, who were previously described by Hanneken et al. (2011) and exhibited a disseminated pattern of skin lesions, and who were also known to be negative for mutation in the KRT5 gene (148040), Basmanav et al. (2014) performed whole-exome sequencing and identified heterozygosity in all 5 affected individuals for 1 of 2 nonsense mutations or a splice site mutation, respectively, in the POGLUT1 gene (615618.0001-615618.0003). Screening additional DDD patients revealed mutations in 7 more patients, including a patient previously diagnosed as having generalized solar lentigines (Mauerer et al., 2010) (see, e.g., 615618.0004 and 615618.0005).

Genotype/Phenotype Correlations

Basmanav et al. (2014) observed prominent involvement of nonflexural areas in DDD patients with mutations in the POGLUT1 gene, in contrast to patients with mutations in KRT5 who present with typical dominant involvement of flexural folds.