CLINICAL CHARACTERISTICS OF A CHROMOSOME 17-LINKED RAPIDLY PROGRESSIVE FAMILIAL FRONTOTEMPORAL DEMENTIA

Objective: To describe symptoms, signs, neuroimaging results, and neur opathologic findings in patients from a family with chromosome 17q21-l inked autosomal dominant frontotemporal dementia. Design: Multiple cas e report with genetic investigations. Subjects: The disease was observ ed in a Swedish family and documented in 3 generations. Four siblings are described in this article. Results: A rapidly progressive dementia with genetic linkage to chromosome 17q21 was observed, The mean age o f onset was 51 years and the average duration of disease to death was 3 years, Two patients started with speech disturbances leading to a pr ogressive, nonfluent aphasia, 1 patient had onset symptoms of leg apra xia and akinesia and muscular rigidity, and in 1 patient reckless driv ing was the first symptom. Loss of spontaneous speech developed later in all patients and emotional bluntness in 3 of the patients. Cerebral perfusion was decreased in the frontal areas in all patients. In the person with apraxia as the onset symptom, the cerebral blood flow was also diminished in the left hemisphere, where a slight atrophy was det ected on magnetic resonance imaging scans. At the postmortem examinati on, slight gliosis of the parietal lobes was observed in this patient. In all patients there was a frontocentral degeneration of the cortex with discrete microvacuolation and gliosis. Conclusion: Clinical featu res of frontotemporal dementia, parkinsonism, an early age of onset, a rapid disease progression, and variable onset symptoms were seen in t hese patients. Two other clinically distinct diseases, dementia with p allido-ponto-nigral degeneration and a disinhibition-dementia-parkinso nism-amyotrophy complex, have recently been mapped to chromsome 17q21. In the family described in this article, genetic linkage was detected to the same region, suggesting the possibility that these diseases ma y originate from pathogenic mutations in the same gene.