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Neurology 2002;59:1187-1196
© 2002 American Academy of Neurology

Phenotypic features of myoclonus-dystonia in three kindreds

D. O. Doheny, MS, M. F. Brin, MD, C. E. Morrison, PhD, C. J. Smith, MS, R. H. Walker, MB ChB, PhD, S. Abbasi, MD, B. Müller, MD, J. Garrels, BS, L. Liu, BS, P. de Carvalho Aguiar, MD, K. Schilling, MS, P. Kramer, PhD, D. de Leon, MS, D. Raymond, MS, R. Saunders-Pullman, MD, C. Klein, MD PhD, S. B. Bressman, MD, B. Schmand, PhD, M. A.J. Tijssen, MD, L. J. Ozelius, PhD and J. M. Silverman, PhD

From the Departments of Neurology (Drs. Brin, Morrison, Walker, Abbasi, and D. Doheny) and Psychiatry (Dr. Silverman and C. Smith), Mount Sinai School of Medicine, New York, NY; Allergan, Inc. (Dr. Brin), Irvine, CA; Department of Neurology (Dr. Walker), Veterans Administration Medical Center, Bronx, NY; Department of Neurology (Drs. Müller, Klein, and J. Garrels), Medical University of Lübeck, Germany; Department of Molecular Genetics (Drs. de Carvalho Aguiar, Ozelius, and L. Liu), Albert Einstein College of Medicine, Bronx, NY; Department of Neurology (Dr. Kramer and K. Schilling), Oregon Health Sciences University, Portland; Department of Neurology (Drs. Saunders-Pullman, Bressman, D. de Leon, and D. Raymond), New York Beth Israel Medical Center, New York, NY; and Academic Medical Center (Drs. Schmand and Tijssen), Amsterdam, the Netherlands.

Address correspondence and reprint requests to Dana O. Doheny, Department of Neurology, Mount Sinai School of Medicine, Annenberg 14-51A, Box 1052, New York, NY 10029; e-mail: Dana.Doheny{at}mssm.edu

Background: Myoclonus-dystonia (M-D) is a movement disorder with involuntary jerks and dystonic contractions. Autosomal dominant alcohol-responsive M-D is associated with mutations in the -sarcoglycan gene (SGCE) (six families) and with a missense change in the D2 dopamine receptor (DRD2)gene (one family).

Objective: To investigate the clinical phenotype associated with M-D including motor symptoms, psychiatric disorders, and neuropsychological deficits.

Methods: Fifty individuals in three M-D families were evaluated and a standardized neurologic examination and DNA analysis were performed. Psychiatric profiles were established with the Diagnostic Interviews for Genetic Studies (DIGS) and the Yale-Brown Obsessive-Compulsive Scale (YBOCS). Cognition was evaluated with standardized neuropsychological tests.

Results: Distinct truncating mutations in the SGCE gene were identified in each family. Additionally, a missense alteration in the DRD2 gene was previously found in one family. Motor expression was variable, with onset of myoclonus or dystonia or both affecting the upper body and progression to myoclonus and dystonia in most cases. Psychiatric profiles revealed depression, obsessive-compulsive disorder, substance abuse, anxiety/panic/phobic disorders, and psychosis in two families, and depression only in the third family. Averaged scores from cognitive testing showed impaired verbal learning and memory in one family, impaired memory in the second family, and no cognitive deficits in the third family.

Conclusions: Cognitive deficits may be associated with M-D. Psychiatric abnormalities correlate with the motor symptoms in affected individuals. Assessment of additional M-D families with known mutations is needed to determine whether these are characteristic phenotypic manifestations of M-D.

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