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Raji P. Grewal, MD; Madhureeta Achari, MD; Tohru Matsuura, MD; Alberto Durazo, MD; Emilio Tayag, MD; Lan Zu, PhD; Stefan M. Pulst, MD; Tetsuo Ashizawa, MD

Arch Neurol. 2002;59:1285-1290.

Background  Spinocerebellar ataxia type 10, an autosomal dominant disease characterized by ataxia and seizures, is caused by a large expansion of an unstable ATTCT pentanucleotide repeat.

Objectives  To characterize the phenotypic expression of spinocerebellar ataxia type 10 and to examine the genotype-phenotype correlations in 2 large families.

Design  Clinical characterization and genotype-phenotype correlation.

Setting  Studies at 2 medical schools with private practice referral.

Patients  Twenty-two affected individuals from 2 large Mexican American pedigrees.

Results  Of the 22 individuals, ataxia was the initial symptom in 21; seizure disorders developed in 11, mostly within several years following the onset of ataxia. The seizure frequency was different in the 2 families: 3 (25%) of 12 had seizures in family 1, and 8 (80%) of 10 had seizures in family 2 (P = .01). A brain magnetic resonance imaging or computed tomographic scan showed cerebellar atrophy in all patients examined. An electroencephalogram demonstrated epileptiform discharges in 4 of 8 patients studied. Although anticipation was apparent in both families, only family 1 showed a strong inverse correlation between age of onset and repeat number (r² = 0.79, P = .001). In family 1, 8 transmissions, of which 7 were paternal, resulted in an average gain of 1940 repeats. In contrast, despite anticipation, 2 affected male subjects transmitted their expanded alleles to 8 progenies, with an average loss of 755 repeats, in family 2.

Conclusions  Seizure is an integral part of the spinocerebellar ataxia type 10 phenotype, with documented morbidity and mortality. Family-dependent factors may alter the frequency of the seizure phenotype and the pattern of intergenerational repeat size changes, making the genotype-phenotype correlation complex.

From the New Jersey Neuroscience Institute, Seton Hall University, Edison (Dr Grewal); the Department of Neurology, Baylor College of Medicine, and the Veterans Affairs Medical Center, Houston, Tex (Drs Matsuura and Ashizawa); the Department of Neurology, University of Southern California, Los Angeles (Dr Tayag); and Rose Moss Laboratory for Parkinson and Neurodegenerative Diseases, Burns and Allen Research Institute, Division of Neurology, Cedars-Sinai Medical Center, University of California, Los Angeles, UCLA School of Medicine, Los Angeles (Drs Zu and Pulst). Drs Achari and Durazo are in private practice in Houston and Tijuana, Calif, respectively.

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