Dyschromatosis Universalis Hereditaria (DUH) is a form of dyschromatosis, a group of cutaneous conditions characterized by the simultaneous presence of both hyper- and hypo-pigmented macules, many of which are small in size and irregular in shape. DUH is a clinically heterogeneous disorder typified by a generalized distribution of this mottled pigmentation, presenting as a generalized leukomelanoderma, with relative sparing of the face, palms, and soles. The age of onset of these lesions is usually in the first few months of life. Some affected patients have shown systemic abnormalities, including short stature, high frequency deafness, erythrocyte, platelet and tryptophan metabolism abnormalities, bilateral glaucoma, cataract, and grand mal seizures.
Histopathology of the lesions shows a variable degree of pigmentary incontinence. The exact etiology of this disorder is unknown. However, studies seem to point towards an inherent abnormality of melanosomes or a defect in melanocyte processing. DUH occurs most commonly among the Japanese. However, there have been sporadic reports from other populations as well.
Bukhari et al. (2006) reported five cases of DUH in a Saudi Arabian Bedouin family. Interestingly, the condition in this family seemed to follow an autosomal recessive mode of inheritance. There were four affected children in this family; two boys and two girls. The unaffected parents were consanguineous, and had three other unaffected children. The patients presented with asymptomatic, multiple bilaterally symmetrical, progressive hypopigmented, depigmented and hyperpimented macules all over the skin that started during infancy or childhood. The hair color of the affected patients was light brown, as opposed to black in the unaffected family members. Biopsy of the lesions showed basal layer hypermelanosis with pigmentary incontinence in some areas. The paternal grandmother of these children was also seen to have similar skin problems. All patients were reported to have normal developmental milestones, except for delayed speech and learning difficulties in one affected boy. Bukhari et al. (2006) made a diagnosis of DUH in the patients.
Stuhrmann et al. (2008) undertook an investigation of the molecular genetic etiology of the condition in the family of Bukhari et al. (2006). Neither known loci on chromosome 1q or 6q were found to be relevant to the condition in the Saudi family. The ADAR gene on chromosome 1q did not show any mutations in the affected patients, and haplotype analysis showed a lack of marker co-segregation with the disease in both candidate gene regions. However, genome wide analysis using a SNP array pointed to a novel putative locus for the condition on chromosome 12q21-q23, with a maximum LOD score of 3.4. The candidate interval thus identified spans a region of 20.9 Mb and contains 125 known or predicted genes. The most likely candidate gene in this region was presumed to be the Pro-Melanin-Concentrating Hormone (PMCH) gene. However, no mutations were found in the introns of this gene in the patients.