DENTATORUBRAL-PALLIDOLUYSIAN ATROPHY (DRPLA) - CLINICAL, GENETIC, ANDNEURORADIOLOGIC STUDIES IN A FAMILY

The clinical, genetic, and neuroradiologic characteristics of dentator ubral-pallidoluysian atrophy (DRPLA) are delineated in six patients fr om three generations of a Japanese family. The clinical characteristic s of the disease varied, the age at onset depending on patients with j uvenile-onset were characterized by myoclonus, epilepsy, and mental re tardation whereas cerebellar ataxia, choreoathetosis, and dementia wer e typical of adult- and senile-onset patients. All affected individual s showed one expanded allele with the repeat number of CAG at the DRPL A locus, ranging from 58 to 82, and a normal allele, ranging from 10 t o 21. The most severely affected patient, a case of maternal transmiss ion and with the largest allele, became bedridden in a vegetative stat e by age 12. On the CT and MRI, varying degrees of brain atrophy were present in all patients. T2-weighted MRI in patients with senile-onset showed symmetric high-signal lesions in the cerebral white matter, gl obus pallidus, thalamus, midbrain, and pens. However, MRI in younger p atients revealed no such lesions and CT failed to demonstrate lesions in the globus pallidus and brain stem. Thus, intrafamilial heterogenei ty of DRPLA was also evident on MRI. High-signal lesions involving bat h, subcortical white matter and thalamus may be characteristics of sen ile-onset patients and may correlate with their dementia.