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NEUROLOGY 1994;44:1878
© 1994 American Academy of Neurology

Clinical characteristics of a family with chromosome 17-linked disinhibition-dementia- parkinsonism-amyotrophy complex

T. Lynch, MRCPI, M. Sano, PhD, K. S. Marder, MD, K. L. Bell, MD, N. L. Foster, MD, R. F. Defending, MD, A.A.F. Sima, MD, PhD, C. Keohane, FRCPath, T. G. Nygaard, MD, S. Fahn, MD, R. Mayeux, MD, L. P. Rowland, MD and K. C. Wilhelmsen, MD, PhD

Department of Neurology, Neurological Institute (Drs. Lynch, Sano, Marder, Bell, Nygaard, Fahn, Mayeux, Rowland, and Wilhelmsen), the Departments of Neuropathology (Dr. Defendini), Psychiatry (Dr. Mayeux), and Public Health (Dr. Mayeux), Gertrude Sergievsky Center (Drs. Sano, Marder, Bell, and Mayeux), and Alzheimer Disease Research Center (Drs. Sano, Marder, Bell, and Mayeux), Columbia-Presbyterian Medical Center, New York, NY; the Departments of Neurology (Dr. Foster), and Pathology and Internal Medicine (Dr. Sima), the University of Michigan Medical Center, Ann Arbor, MI; and the Department of Neuropathology (Dr. Keohane), Cork Regional Hospital, Wilton, Cork, Ireland.

We studied the clinical features, pathology, and molecular genetics of a family (Mo) with an autosomal dominant disinhibition, frontal lobe dementia, parkinsonism, and amyotrophy. We examined seven affected members and gathered clinical information on another six. The mean onset was at age 45 years. Personality and behavioral changes (disinhibition, withdrawal, alcoholism, hyperphagia) were the first symptoms in twelve. There was early memory loss, anomia, and poor construction with preservation until late of orientation, speech, and calculations. All affected members examined had rigidity, bradykinesia, and postural instability. Mean duration to death was 13 years. We studied the neuropathology of six individuals, five of whom had been examined in life. There was atrophy and spongiform change in the frontotemporal cortex, and neuronal loss and gliosis in the substantia nigra and amygdala. Two individuals, including one with fasciculations and muscle wasting, had anterior horn cell loss. There were no Lewy bodies, neurofibrillary tangles, or amyloid plaques. We call this disorder the "disinhibition-dementia-parkinsonism-amyotrophy complex" (DDPAC), based on the clinical syndrome found in this family and linkage to chromosome 17.

Address correspondence and reprint requests to Dr. Kirk C. Wilhelmsen, Department of Neurology, Neurological Institute, 710 West 168th Street, New York, NY 10032.

Supported by the Herbert Irving Professorship, the Parkinson's Disease Foundation, the Dystonia Medical Research Foundation, NIH grants AG07232 and AG08702, and the Michigan Alzheimer's Disease Research Center (NIH AG08671).

Received December 28, 1993. Accepted in final form March 22, 1994.




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