Dowling-Degos disease (DDD) is an autosomal dominant genodermatosis characterized by reticular pigmentation, usually in a flexural distribution. However, generalized DDD can also occur, with numerous hypopigmented or erythematous macules and papules on the neck, chest, and abdomen. The ... Dowling-Degos disease (DDD) is an autosomal dominant genodermatosis characterized by reticular pigmentation, usually in a flexural distribution. However, generalized DDD can also occur, with numerous hypopigmented or erythematous macules and papules on the neck, chest, and abdomen. The histopathology of DDD shows characteristic thin branch-like patterns of epidermal downgrowth (summary by Li et al., 2013). - Review of Reticulate Pigment Disorders Muller et al. (2012) reviewed the spectrum of reticulate pigment disorders of the skin, tabulating all reported cases of patients with Dowling-Degos disease, reticulate acropigmentation of Kitamura (RAK), reticulate acropigmentation of Dohi (DSH, RAD; 127400), Galli-Galli disease (GGD), and Haber syndrome (HS). Of 82 cases, 26 (31.7%) were clinically diagnosed as DDD, 13 (15.9%) as RAD, 11 (13.4%) as GGD, 8 (9.8%) as RAK, and 8 (9.8%) as HS; in addition, 16 (19.5%) of the cases showed overlap between DDD and RAK. Muller et al. (2012) also published photographs of an affected individual exhibiting an overlap of clinical features of DDD, GGD, RAD, and RAK. The authors noted that in reticulate disorders of the skin, the main disease entity is DDD, with a subset of cases exhibiting acantholysis (GGD), facial erythema (HS), or an acral distribution (RAD; RAK). Muller et al. (2012) concluded that all reticulate pigment diseases of the skin are varying manifestations of a single entity. For a discussion of genetic heterogeneity of reticulate pigment disorders, see 179850.
Li et al. (2013) studied 2 Chinese families with generalized Dowling-Degos disease. The proband in the first family was a 49-year-old woman with a 20-year history of reticular hyperpigmentation that began on her neck and consisted of spots ... Li et al. (2013) studied 2 Chinese families with generalized Dowling-Degos disease. The proband in the first family was a 49-year-old woman with a 20-year history of reticular hyperpigmentation that began on her neck and consisted of spots that gradually increased in number and size and showed deeper coloration, without subjective symptoms. The skin lesions became darker in summer and lightened in winter. Affected relatives included her father, paternal grandfather, 3 sisters, 2 brothers, and 2 nephews, as well as a paternal aunt, female cousin, and that cousin's son. All affected family members had hyperpigmentation on the skin of the neck, wrist, chest, inguinal area, and inner thighs; some of them also had hypopigmented macules and hyperkeratotic dark brown papules on the neck, chest, and back. Histologic examination of a skin biopsy from the proband showed hyperkeratosis with multiple horny follicular plugs and papillary epidermal downgrowth with abnormal basal pigment-granule distribution. Sporadic melanin granules and melanophages were seen in the superficial layer of the dermis, and there was an uneven distribution of melanin in the epidermis. Electron microscopy revealed that all melanocytes were small and lacked melanosomes; however, keratinocytes showed normal keratin filaments and interactions with hemidesmosomes and desmosomes. In the second family, the proband was a 53-year-old woman who had brown macules over flexural areas for over 32 years, beginning on the neck and gradually increasing in size. Pigmented and hypopigmented macules then spread to the face, bilateral axillae, popliteal fossae, and groin, without subjective symptoms. Some of the macules merged and organized in a reticular pattern, and hyperkeratotic dark-brown papules were observed on the axillae bilaterally. Skin biopsy from the neck showed epidermal papillomatous hyperkeratosis with keratotic plugs, trochanterellus elongation with abnormal basal pigment-granule distribution, and perivascular lymphohistiocytic infiltration of the superficial dermis. Her deceased mother was also affected. Li et al. (2013) stated that there were no obvious anomalies in other organs or systems in affected individuals from these 2 families.
In a 4-generation Chinese family with Dowling-Degos disease mapping to chromosome 20, Li et al. (2013) performed exome sequencing of 1 affected individual and identified a heterozygous nonsense mutation in the POFUT1 gene (E144X; 607491.0001) that was confirmed ... In a 4-generation Chinese family with Dowling-Degos disease mapping to chromosome 20, Li et al. (2013) performed exome sequencing of 1 affected individual and identified a heterozygous nonsense mutation in the POFUT1 gene (E144X; 607491.0001) that was confirmed by Sanger sequencing, cosegregated with disease in the family, and was not found in 600 Chinese controls. Screening of the POFUT1 gene in the proband from a second Chinese family with DDD revealed a 1-bp deletion (482delA; 607491.0002) that was not found in unaffected family members or in 600 Chinese controls.