Clinical characteristics of a chromosome 17-linked rapidly progressive familial frontotemporal dementia
H. Basun, O. Almkvist, K. Axelman, A. Brun, T. A. Campbell, J. Collinge, C. Forsell, S. Froelich, L. O. Wahlund, L. Wetterberg and L. Lannfelt
Department of Clinical Neuroscience and Family Medicine, Karolinska Institutet, Huddinge University Hospital, Sweden.
OBJECTIVE: To describe symptoms, signs, neuroimaging results, and
neuropathologic findings in patients from a family with chromosome
17q21-linked autosomal dominant frontotemporal dementia. DESIGN: Multiple
case report with genetic investigations. SUBJECTS: The disease was observed
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 of onset was
51 years and the average duration of disease to death was 3 years. Two
patients started with speech disturbances leading to a progressive,
nonfluent aphasia, 1 patient had onset symptoms of leg apraxia and akinesia
and muscular rigidity, and in 1 patient reckless driving 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 detected on magnetic resonance
imaging scans. At the postmortem examination, 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 features of frontotemporal dementia,
parkinsonism, an early age of onset, a rapid disease progression, and
variable onset symptoms were seen in these patients. Two other clinically
distinct diseases, dementia with pallido-ponto-nigral degeneration and a
disinhibition-dementia-parkinsonism-amyotrophy complex, have recently been
mapped to chromosome 17q21. In the family described in this article,
genetic linkage was detected to the same region, suggesting the possibility
that these diseases may originate from pathogenic mutations in the same
gene.
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