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Dyschromatosis symmetrica hereditaria
Dyschromatosis symmetrica hereditaria
Pathogenesis and histologic features Genetic studies in a family with the disease have suggested that the responsible gene may map to the same chromosomal region as that for the Naegeli-Franceschetti-Jadassohn syndrome on chromosome 17q21.8 Mutations in keratin 14 occur in both, and these conditions may be part of the same spectrum.9 The diseases are regarded as variants of allelic ectodermal dysplasia.10,11
The histologic features have not been described in detail. Pigment incontinence and melanophages are conspicuous but the epidermis appears normal.1 Transmission electron microscopy of hair shafts in two affected siblings revealed no abnormalities.12
Clinical features Dyschromatosis symmetrica hereditaria (DSH) (symmetrical dyschromatosis of the extremities, reticulate acropigmentation of Dohi) is a rare condition with an autosomal dominant or (more rarely) a recessive pattern of inheritance.1โ6 It is characterized by pigmented and hypopigmented macules on the extremities presenting in a reticulate pattern, developing during infancy and childhood, and persisting for life. Lesions occur particularly on the dorsum of the hands, forearms, and feet. Involvement of the face may be seen. The disease occurs mainly in Oriental patients (mainly Japanese and Chinese) but has also been reported in Europeans, Indians, Afro-Caribbeans, and Middle Eastern populations.3 In some patients there are associated neurological abnormalities, including brain calcification, seizures, autism, mental deterioration, and dystonia.7 Neurological changes are only described in Aicardi-Goutiรจres syndrome 6, also caused by mutations in the same gene as DSH (see below). As some patients present with skin changes and neurological abnormalities, it has been proposed that both
1008 Disorders of pigmentation
conditions are phenotypic variants of the same disease.8 A case associated with intracranial hemangiomas and a further case with acral hypertrophy have been described.9,10
Pathogenesis and histologic features Mutations of the double-stranded RNA-specific adenosine deaminase gene (ADAR1 gene) in chromosome 1q21โ22 have been found in patients with the disease.11โ16 More than 100 mutations have been described.17 The mechanism of pigmentation is unknown.
associated with acute or chronic bleeding, often resulting in anemia, and may also be complicated by intestinal obstruction and intussusception.7 Polyps occur mainly in the jejunum and ileum, followed by the stomach, duodenum, and colon.
The disease is also associated with an increase in the incidence of malignancies involving the small intestine, stomach, pancreas, breast, esophagus, cervix, testicles (Sertoli cell tumors), and ovaries (sex cord tumors).8
Some patients present only with pigmented macules and no polyps, and these have been described as isolated mucocutaneous melanotic pigmentation.9 Female patients with this presentation do seem to be at increased risk of developing breast and gynecological malignancy.9
Biopsies from hypopigmented macules reveal absence of melanin and this correlates with abnormal melanocytes on electron microscopy.2 Histology of hyperpigmented areas shows an increase in the deposition of basal melanin and this is reflected by an increase in the number of melanocytes on electron microscopy.2