Wednesday, July 19, 2017

Dyschromatosis symmetrica hereditaria

Dutta A, Ghosh SK, Basu S, Mandal RK. Dyspigmentation of Skin as a Clue to the Diagnosis of Dystonia. Pediatr Neurol. 2017 Apr 20. pii: S0887-8994(17)30099-1. doi: 10.1016/j.pediatrneurol.2017.04.015. [Epub ahead of print]

This ten-year-old girl presented with a history of difficulty walking since her early childhood. She was evidently normal until age ten months. Subsequently, her parents noticed that she became less responsive to stimuli and there was a decrease in vocalization. She exhibited regression of developmental milestones. Her birth and perinatal history was normal, and there was no history of convulsion or jaundice. There had been no febrile episode or use of medication preceding the onset of her illness. Her parents and a sibling were healthy.

Examination revealed a triangular face and short stature (122 cm, less than the 3rd percentile). She was also underweight (22.5 kg, less than the 3rd percentile). However, she appeared alert, responding to all commands with a hypophonic voice along with dystonic speech. The girl had a dystonic gait particularly involving the right lower limb along with dystonic posture of right foot. Both arms exhibited dystonic posturing (right more than left) which used to be more prominent during walking. Muscle power and tendon reflexes were normal. Planter responses were flexor. Cutaneous examination documented reticulate hypopigmentated and hyperpigmentated macules over the dorsum of the hands and feet. Multiple freckle-like hyperpigmentations were also noted on the face, both lower thighs, and knees.  For these pigmentary changes her parents had never sought medical attention. Systemic examination including musculoskeletal system was normal. Ophthalmologic examination was also noncontributory.

Laboratory parameters, including routine blood, liver and renal function tests, serum ceruloplasmin, 24-hour urinary copper, serum lactate, pyruvic acid, calcium, vitamin D, phosphorus, magnesium, thyroid, and parathormone levels were all within normal limits. Computed tomography of brain and an electroencephalograph were normal. Magnetic resonance imaging (MRI) of brain revealed bilateral hyperintensities of the putamina. In addition, there were a few small discrete hyperintense lesions in the subcortical frontal and parietal areas.

In view of the neurological manifestations, Wilson disease was initially the provisional diagnosis. However, her normal ceruloplasmin level, normal 24-hour urinary copper level, normal liver function tests, and the absence of Kayser–Fleischer rings on slit lamp examination excluded Wilson disease. We also considered other causes of childhood dystonia especially primary generalized dystonia, pantothenate kinase–associated neurodegeneration, Huntington disease, and Leigh syndrome in the differential diagnosis…

The differential diagnosis of cutaneous pigmentary changes may include dyschromatosis symmetrica hereditaria (DSH), dyschromatosis universalis hereditaria, reticulate acropigmentation of Kitamura, a mild form of xeroderma pigmentosum, and Dowling-Degos disease among others.

On the basis of the clinical and histopathological findings, the diagnosis of DSH with dystonia was made.

DSH is a dermatologic pigmentary disorder characterized by reticulate hypopigmented and hyperpigmented macules distributed on the dorsal aspects of the hands and feet. The pigmentation is asymptomatic, begins in infancy or childhood, and may gradually increase in depth and extent to the dorsal aspect of the extremities. In a fully established lesion, the pigmentation persists lifelong without any further change in distribution or color. Some patients show freckle-like macules on the face. No pigment macules are observed on the palm, sole, or mucosa. The lesions did not include telangiectasia, atrophy, or scaling. Histopathologic findings usually show abundant melanin deposition in the keratinocytes in the hyperpigmented macules, as in this girl. Reduced melanization occurs in the hypopigmented macules. 

DSH exhibits an autosomal-dominant pattern of inheritance with high penetrance. However, the disorder also occurs sporadically, as in this child. A heterozygous mutation in the adenosine deaminase acting on RNA1gene ( ADAR1 ) located on chromosome 1q21.3 probably causes the disease. 

In general, DSH is usually restricted to the skin only. A few previous reports have described dystonia, mental deterioration, and brain calcification in association with DSH.  Besides the aforementioned neurological features, seizures, developmental regression, autistic features, mood disorder, behavioral problems, feeble vocalization, and gait abnormalities have also been described.

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