CLINICAL CHARACTERISTICS OF A FAMILY WITH CHROMOSOME 17-LINKED DISINHIBITION-DEMENTIA-PARKINSONISM-AMYOTROPHY COMPLEX

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 mem bers 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 twel ve. There was early memory loss, anemia, and poor construction with pr eservation until late of orientation, speech, and calculations. All af fected members examined had rigidity, bradykinesia, and postural insta bility. Mean duration to death was 13 years. We studied the neuropatho logy of six individuals, five of whom had been examined in life. There was atrophy and spongiform change in the frontotemporal cortex, and n euronal loss and gliosis in the substantia nigra and amygdala. Two ind ividuals, including one with fasciculations and muscle wasting, had an terior horn cell loss. There were no Lewy bodies, neurofibrillary tang les, or amyloid plaques. We call this disorder the ''disinhibition-dem entia-parkinsonism-amyotrophy complex'' (DDPAC), based on the clinical syndrome found in this family and linkage to chromosome 17.