A pediatric patient with sporadic dentatorubral pallidoluysian atrophy

Introduction 

Dentatorubral pallidoluysian atrophy is an autosomal-dominant neurodegenerative disorder characterized by various combinations of myoclonus, epilepsy, ataxia, choreoathetosis, and dementia [1]. Patients classified as juvenile type are usually diagnosed as manifesting myoclonus epilepsy with severe mental defects and mild cerebellar ataxia. However, it is difficult to diagnose a patient of this type without information on other affected family members. We report a sporadic pediatric case of the juvenile type of dentatorubral pallidoluysian atrophy.

Case report 

A 10-year-old girl had been healthy until the age of 2 years 6 months, when a physical examination re-vealed that she was mentally retarded. She started to experience generalized epileptic seizures at 7 years of age, and neurologic symptoms, such as slurred speech, unsteady gait, and intellectual disturbances, then slowly progressed.

At 10 years of age, she complained of progressive intellectual and motor dysfunction. Her family clinical evaluation revealed no members with ataxia, epilepsy, involuntary movements, psychosis, or other neurodegenerative disease (Fig 1).

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Figure 1. Pedigree of the patient. Roman numerals indicate generations. The proband is indicated by the arrow (IV-2). Closed symbol indicates affected member; open symbols, unaffected members; circles, females; squares, males; and diagonal lines; deceased persons. III-2, 39 years, patient’s father; III-4, 38 years, patient’s mother.

Neither her 39-year-old father nor her 38-year-old mother manifested any neurologic abnormalities or epilepsy. She had pronounced mental retardation, and her intelligence quotient corresponded to that of a 3year-old child. Her speech was slurred. She manifested full-range external ocular movements and no nystagmus. Her pharyngeal reflex was weak. No myoclonus or tremors were evident. All four of her limbs were hypotonic, and motor weakness was present. She exhibited ataxia in all four limbs and her trunk and was unable to stand or walk. Babinski’s sign was not present, but deep tendon reflexes were slightly accentuated. Electroencephalogram demonstrated frequent multiple spikes in the right occipital area; photoconvulsive responses with photic stimulation of 9, 12, 15, and 18 Hz were also demonstrated. In brain magnetic resonance imaging, no abnormal signal lesions were detected. Atrophic changes in the cerebral cortex, cerebellum, and brainstem were unremarkable. Deoxyribonucleic acid analysis of the dentatorubral pallidoluysian atrophy gene of leukocytes was performed in accordance with a previously reported polymerase chain reaction method [2] (Fig 2). The CAG trinucleotide repeat numbers were 61/15. We did not examine her parents’ genes.

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Figure 2. Polyacrylamide gel analysis of the polymerase chain reaction–amplified product containing the trinucleotide repeat tract in a normal control (lane A, 17/12 CAG repeats), our patient (lane B, 61/15), and two patients with dentatorubral pallidoluysian atrophy (disease control; lanes C and D, 73/12 and 62/15, respectively). Lanes M1 and M2, markers.

Sporadic cases of dentatorubral pallidoluysian atrophy have been observed, but their occurrence is rare [3], [4]. The age at diagnosis of these patients ranges from 22 to 57 years, and pediatric cases are not included. To clarify the molecular mechanisms that underlie the occurrence of sporadic cases, many such cases should be analyzed. From an ethical point of view, however, DNA analysis of the dentatorubral pallidoluysian atrophy gene of both parents of a sporadic patient may be limited.