Dyschromatosis Symmetrica Hereditaria

A number sign (#) is used with this entry because dyschromatosis symmetrica hereditaria (DSH) is caused by heterozygous mutation in the DSRAD gene (ADAR; 146920) on chromosome 1q21.

Description

Dyschromatosis symmetrica hereditaria (DSH), also called symmetric dyschromatosis of the extremities and symmetric or reticulate acropigmentation of Dohi (Komaya, 1924), is characterized by hyperpigmented and hypopigmented macules on the face and dorsal aspects of the extremities that appear in infancy or early childhood. DSH generally shows an autosomal dominant pattern of inheritance with high penetrance. The condition has been reported predominantly in Japanese and Chinese individuals.

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 (see DDD1; 179850), reticulate acropigmentation of Kitamura (RAK; 615537), reticulate acropigmentation of Dohi (RAD), 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.

Genetic Heterogeneity of Reticulate Pigment Disorders

For a discussion of genetic heterogeneity of reticulate pigment disorders, see 179850.

Clinical Features

Patrizi et al. (1994) described a 9-year-old Caucasian girl with a mixture of hyperpigmented and hypopigmented macules on the backs of the feet. Two brothers had the same lesions, and all had small freckle-like pigmented macules on their face. The father showed large symmetrical hypopigmented vitiligo-like macules which had been present on the backs of his hands and the tops of his feet since childhood. Large symmetrical hypopigmented vitiligo-like macules were found also around his eyes and mouth, on his knees, and on his penis. These hypopigmented macules had progressively widened after the age of 28 years. The 9-year-old daughter had, since the age of 7 years, also shown a neurologic disorder diagnosed as idiopathic torsion dystonia. In all 4 patients, no cellular abnormality in DNA repair was demonstrated, thus excluding a mild form of xeroderma pigmentosum. Torsion dystonia (TYD1; 128100) maps to 9q34. Because of the family of Patrizi et al. (1994), the DSH gene was hypothesized to be located on chromosome 9, but studies of 3 Japanese families with DSH by Kono et al. (2000) excluded chromosome 9.

Oyama et al. (1999) reported a Japanese family with DSH. The proband was an 11-year-old male, born following a normal pregnancy and delivery. At the age of 1 year, he developed pea-sized pigmented macules on the face. The small hyperpigmented and hypopigmented macules spread gradually on the dorsal aspects of the extremities. The number of skin lesions increased until he was 4 years of age. The mother, a 50-year-old woman, had had an asymptomatic mixture of hyperpigmented and hypopigmented small macules on the backs of her hands and feet as well as scattered small pigmented macules on her face since childhood. Her father, twin brothers of her father, and her grandmother had also had the same skin lesions.

Oyama et al. (1999) reviewed 185 cases of DSH reported since 1923. The differential diagnosis was considered to include dyschromatosis universalis hereditaria (DUH; 127500). DUH was once considered to be a generalized form of DSH; however, Suenaga (1952) pointed out that skin lesions in DUH appear predominantly on the trunk. DSH can closely resemble a mild form of xeroderma pigmentosum (see 278700).

In Italy, Danese et al. (1997) observed a family with affected members in at least 3 generations. The proband was a 21-year-old white woman who had progressive reticulate hyper- and hypopigmentation on the volar surface of the forearms and the dorsa of the hands. There were no pits or breaks in the epidermal ridge pattern on the palms.

Urabe and Hori (1997) described a Japanese family with DSH with an autosomal recessive inheritance pattern. Alfadley et al. (2000) described 3 black sibs from the Middle East, a 20-year-old male and his 19- and 18-year-old sisters, who had progressive reticulate hyperpigmented and hypopigmented macules over the dorsa of hands and feet, which began in early childhood. There were no palmar pits or breaks of the epidermal rete ridge pattern, nor was there a family history of any pigmentary skin disease. Findings from 3 skin biopsies from 1 patient were consistent with DSH. These finding suggested to the authors that DSH may be inherited in an autosomal recessive manner.

Chao et al. (2006) reported 3 affected members of a Taiwanese family segregating DSH. Strict avoidance of sunlight by the proband and her affected daughter led to improvement in the skin lesions.

Population Genetics

Miyamura et al. (2003) stated that the prevalence of DSH in the Japanese population is estimated to be 1.5 per 100,000.

Mapping

Zhang et al. (2003) performed a genomewide search in 2 large Chinese families with DSH and identified a locus at chromosome 1q11-q21 with a cumulative maximum 2-point lod score of 8.85 at marker D1S2343 (recombination fraction = 0.00). Haplotype analyses indicated that the disease gene is located within the 11.6-cM region between markers D1S2696 and D1S2635.

Miyamura et al. (2003) performed a genomewide search in 3 families with DSH and mapped the DSH locus to 1q21.3, within a 500-kb critical region bounded proximally by IL6R (147880) and distally by KCNN3 (602983).

Miyamura et al. (2003) suggested that the patients reported by Xing et al. (2003) showing linkage to 6q24.2-q25.2 in fact had dyschromatosis universalis hereditaria, as indicated by photographs showing dyschromatosis over most of their entire bodies.

Molecular Genetics

In affected members of 4 Japanese families segregating DSH, Miyamura et al. (2003) identified heterozygous mutations in the ADAR gene (146920.0001-146920.0004).

In affected members of 6 Chinese multigeneration families and 2 sporadic patients with DSH, Zhang et al. (2004) identified 7 novel heterozygous mutations in the ADAR gene.