Dyschromatosis Symmetrica Hereditaria
DSH is characterized by a symmetrical distribution of hyper- and hypopigmented macules over the dorsa of the hands and feet, with occasionally the face affected as well (Figure 6). The dyschromatosis appears in infancy or early childhood, and although it commonly stops spreading before adolescence, it lasts for life (as with DUH). Histologically, there may be a focal increase or decrease in melanin content or in the numbers of melanocytes of the basal layer (depending on the hyper- or hypopigmented lesion biopsied), which is also similar to DUH. Most patients with DSH are of an East Asian background, although rare cases have been reported in non-East Asian individuals.[43,44] Zhang et al. first mapped the gene for DSH to 1q11-1q21; shortly thereafter, Miyamura et al. found that mutations in the RNA-specific adenosine deaminase (DSRAD) gene, also called ADAR1, underlie DSH. DSH was initially considered to be a focal variant of DUH, but the clinical features of DUH and DSH are distinct (DUH occurs predominantly on the trunk, whereas DSH usually occurs only on the extremities) and they have not been found in the same pedigrees. Moreover, pathogenic ADAR1 mutations have not been found in cases of DUH and ABCB6 defects did not appear in patients with DSH.
Clinical features of dyschromatosis symmetrica hereditaria in a patient with an ADAR1 mutation: hyper- and hypopigmented macules on extremities, face and knee joints.
Aicardi–Goutières syndrome type 6 (AGS; OMIM 615010), an autosomal recessive autoimmune disorder that affects the nervous system (e.g. intracranial calcification, leucodystrophy and severe developmental delay), was found to be caused by ADAR1 mutation, but dyschromatosis of the skin was absent. Recently, Kono et al. reported a Japanese case of DSH with the AGS phenotype (neurological symptoms and brain calcification) resulting from compound heterozygous ADAR1 mutations; they proposed that homozygous or compound heterozygous ADAR1 mutations may cause the combination of AGS and DSH in East Asian patients, but cause only AGS in non-East Asian patients. Briefly, the phenotypic variability may predominantly depend on ancestry or the status of the mutation (biallelic or monoallelic mutation) (Table S3; see Supporting Information).
In addition to DUH exhibiting similar dyschromic lesions (distinguished by a diffuse distribution that affects the trunk), mild XP phenotypes with hyper- and hypopigmented macules that mainly affect sun-exposed areas (distinguished by photosensitivity, actinic lesions with atrophy, xerosis and telangiectasia) should also be added to the differential diagnosis.
The dyschromic lesions of DSH are predominantly limited to sun-exposed areas, which clearly affects the appearance of the skin. Current medical treatments have been unsuccessful. Stringent protection from sunlight exposure may decrease the contrast between the hypo- and hyperpigmented macules. Neurological symptoms and brain calcification should be of particular concern in those patients with biallelic ADAR1 mutations.
The British Journal of Dermatology. 2017;177(4):945-959. © 2017 Blackwell Publishing