Updated Review of Genetic Reticulate Pigmentary Disorders

J. Zhang; M. Li; Z. Yao

Disclosures

The British Journal of Dermatology. 2017;177(4):945-959. 

In This Article

Discussion

Although the genetic reticulate pigmentary disorders (except XLRPD, EBS-MP/DPR/NFJS and DC) usually present only pigmentary abnormalities in the skin, and rarely affect other systems, these unsightly diseases pose a severe psychological burden on affected families. Thus, a correct diagnosis is necessary for clinical and genetic counselling, as well as prenatal diagnosis and precision medicine in the future. Here, we propose a diagnostic strategy for these overlapping disorders.

In summary, genetic reticulate pigmentary abnormalities can be divided into generalized and localized types (Table 1). The generalized types of reticulate pigmentary disorders (and respective genes involved) include generalized DDD (KRT5, POFUT1 and POGLUT1), DUH (ABCB6), XLRPD, EBS-MP/DPR/NFJS (KRT5 and KRT14) and SASH1-related phenotypes with lentigines and/or dyschromatosis (SASH1). Generalized DDD can be differentiated from DUH by the onset age of the skin lesions (young adulthood vs. infancy or early childhood), the characteristic pathological findings (thin branch-like patterns of epidermal down growth with or without acantholysis) and the occurrence of hyperkeratotic reddish-brown papules. In affected males, XLRPD presents with an X-linked inheritance mode, distinct facial characteristics and the involvement of multiple systems, whereas IP-like, hyperpigmented lesions are observed in female carriers. SASH1-related lentiginous phenotypes present generalized lentigines predominantly on the face and upper trunk, and can exhibit hyper- and hypopigmentation on the trunk and extremities (Figure 10). The localized type comprises classic DDD (KRT5), DSH (ADAR1), RAK (ADAM10) and DC. Reticulate pigmentations predominantly appear on the flexural region in classic DDD, on the acral skin in RAK and DSH (additionally, patients with DSH exhibit areas of depigmentation) and on the upper chest and/or neck in DC (along with dysplastic nails and oral leucoplakia) (Figure 11).

Figure 10.

Diagnostic algorithm of genetic reticulate pigmentary disorders (generalized type). EBS-MP, epidermolysis bullosa simplex with mottled pigmentation; NFJS, Naegeli–Franceschetti–Jadassohn syndrome; DPR, dermatopathia pigmentosa reticularis; XLRPD, X-linked reticulate pigmentary disorder; DUH, dyschromatosis universalis hereditaria; DDD, Dowling-Degos disease; GGD, Galli-Galli disease; DC, dyskeratosis congenita.

Figure 11.

Diagnostic algorithm of genetic reticulate pigmentary disorders (localized type). DDD, Dowling-Degos disease; GGD, Galli-Galli disease; RAK, reticulate acropigmentation of Kitamura; DSH, dyschromatosis symmetrica hereditaria; DC, dyskeratosis congenita; NFJS, Naegeli–Franceschetti–Jadassohn syndrome; DPR, dermatopathia pigmentosa reticularis.

These characteristic features can provide information for a preliminary diagnosis. Molecular genetic testing for the corresponding causal genes of these diseases can assist in definite and accurate diagnosis.

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