Reticulate pigmented anomaly of the flexures. Case reports and genetic investigation

Abstract

Reticulate pigmented anomaly of the flexures is a pigmented macular disease characterized by punctate, hyperpigmented macules on the flexural areas. Histopathologic findings include acanthosis, keratinization of the follicular infundibulum, and filiform downgrowths of epidermal cells. Examination of a family has revealed the presence of the disease in six members. Analysis of these data suggests that reticulate pigmented anomaly of the flexures is an autosomal dominant genodermatosis with possibly variable penetrance, variable expressivity, and delayed onset.

Dowling-Degos disease associated with squamous cell carcinomas on the dappled pigmentation

“…Our patient revealed characteristic pigmentation uniquely localized to the buttocks, in contrast to the previously reported patients with Dowling–Degos disease who mainly manifested reticular pigmentation of the flexural areas even though they showed hyperpigmentation on the buttock 1,3 , 7 . This pigmentation was not clearly reticulate but rather dappled as pointed out by Wilson Jones and Grice, 1 who noted that less severely affected lesions of Dowling–Degos disease show dappled patterns in varying shades of brown.…”

“…Our patient revealed characteristic pigmentation uniquely localized to the buttocks, in contrast to the previously reported patients with Dowling-Degos disease who mainly manifested reticular pigmentation of the flexural areas even though they showed hyperpigmentation on the buttock. 1,3,7 This pigmentation was not clearly reticulate but rather dappled as pointed out by Wilson Jones and Grice, 1 who noted that less severely affected lesions of Dowling-Degos disease show dappled patterns in varying shades of brown. The other clinical findings consistent with Dowling-Degos disease were comedone-like lesions on the face and back, a finger-like fibroma in the popliteal fossa, dystrophic fingernails, and a large number of seborrhoeic keratosis-like lesions.…”

Is Dowling—Degos disease the same disease as Kitamura's reticulate acropigmentation?

“…Finally, our patient appears to belong to a family in which DDD and ARK are curiously distributed. In the light of the autosomal dominant transmission of DDD (Brown, 1982;Crovato, Nazzari & Rebora, 1983), the mother of our patient should be expected to have produced children with DDD, but in fact the propositus showed both DDD and ARK and her sister showed only ARK. The sole explanation is that the two conditions are different phenotypic expressions of the same genodermatosis.…”

A phenotype combining hidradenitis suppurativa with Dowling-Degos disease caused by a founder mutation in PSENEN

“…Reticulate flexural pigmentation is a hallmark of DDD, although follicular involvement is not uncommon, as evidenced by the presence of epidermoid cysts or pilonidal sinus as well as follicular plugging on histology, amounting to a comedo-like follicular retention cyst. 4,6,24 DDD has been shown to share many clinical features and sometimes to coexist with HS as DDD-HS. Recently, DDD-HS has been shown to result from mutations in PSENEN, encoding a critical component of c-secretase.…”

“…5 Follicular lesions such as epidermoid cysts and pilonidal sinus have also been described. 6 DDD has been shown to result from mutations in at least three genes: KRT5, 7 POFUT1 8 and POGLUT1. 9 Hidradenitis suppurativa (HS) is a relapsing inflammatory disease originating in hair follicles, which follows a chronic course characterized by subcutaneous extension with induration, scarring, destruction of skin appendages and sinus formation.…”