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 fa mily (Mo) with an autosomal dominant disinhibition, frontal lobe dementia, parkinsonism, and amyotrophy. We examined seven affected members and gather ed 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 los s, anomia, and poor construction with preservation until late of orientatio n, speech, and calculations. All affected members examined had rigidity, br adykinesia, and postural instability. Mean duration to death was 13 years. We studied the neuropathology of six individuals, five of whom had been exa mined in life. There was atrophy and spongiform change in the frontotempora l cortex, and neuronal loss and gliosis in the substantia nigra and amygdal a. Two individuals, including one with fasciculations and muscle wasting, h ad anterior horn cell loss. There were no Lewy bodies, neurofibrillary tang les, or amyloid plaques. We call this disorder the "disinhibition-dementia- parkinsonism-amyotrophy complex" (DDPAC), based on the clinical syndrome fo und in this family and linkage to chromosome 17.