[Sisters with early onset hereditary dentatorubral-pallidoluysian atrophy of childhood--DNA analysis and clinicopathological findings].
Two sisters were presented, 16 years old and 12 years old, who showed similar clinical courses. They had had mental retardation since early childhood, and then ataxia began. They suffered from astatic and tonic seizures from early school age, which gradually evolved to intractable epilepsies. Spasticity progressed, and they deteriorated both physically and mentally. They revealed photo-sensitivity; convulsions were induced by the flickering of light. They were attacked by myoclonic seizures as well as choreoathetosis, and became bedridden by the latter part of the elementary school age. There were no fruitful results of any kind from the laboratory examinations for metabolic disorders. EEG showed that the epileptic seizure discharges were induced by photic stimulation; there were frequent 3-4 Hz diffuse spike-and-wave short bursts during waking and sleep periods. MRI findings of the elder sister at the age of 16 revealed remarkable diffuse brain atrophy. Gene analysis showed abnormally enlarged DNA fragments localized on the short arm of chromosome 12. This meant expanded CAG trinucleotide repeats. The younger sister died at the age of 12 years. Autopsy findings revealed degeneration of both dentatorubral and pallidoluysian pathways. There were especially remarkable gliosis and neuronal cell loss in the outer segment of globus pallidus, and moderate neuronal cell loss and typical grumose degeneration in the dentate nucleus. The diagnosis of juvenile-type hereditary dentatorubral-pallidoluysian atrophy was compatible with the pathologic findings. This diagnosis will be made possible before death through the understanding of the clinical symptoms and molecular genetics.
Division of Child Neurology, Kanagawa Children's Medical Center, Yokohama.
S
S
Yamashita
H
H
Iwamoto
M
M
Hara
I
I
Kondo
Y
Y
Shimasaki
K
K
Higashi
S
S
Miyake
M
M
Yamada
D000293:Adolescent; D017668:Age of Onset; D001284:Atrophy; D002648:Child; D004247:DNA / Q000032:analysis*; D005192:Family Health; D005260:Female; D005917:Globus Pallidus / Q000473:pathology; D006801:Humans; D012012:Red Nucleus / Q000473:pathology; D012091:Repetitive Sequences, Nucleic Acid; D013132:Spinocerebellar Degenerations / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology
D004247:DNA