Frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP-17): A clinician's guide

BACKGROUND- Frontotemporal dementias are progressive dementing disorders characterized by prominent behavioral disturbance. Recently, hereditary frontotemporal dementia in several kindreds has been linked to chromosome 17. A consensus conference in 1996 agreed that the illness in affected members of these families was sufficiently similar to constitute a distinct disorder. The name "frontotemporal dementia with parkinsonism linked to chromosome 17" (FTDP-17) was selected to emphasize the shared features in these families that generally includes a progressive and disabling movement disorder. REVIEW SUMMARY- FTDP-17 is an autosomal dominant, presenile, progressive dementia. Presenting complaints can include apathy, psychosis, late-onset alcoholism, parkinsonism, and muscle atrophy suggesting motor neuron disease. The broad array of possible symptoms may obscure the hereditary nature of the disease, requiring a careful review of family history. This appears to be a rare disorder, although at least 43 affected families have been identified. FTDP-17 can be caused by mutations in expressed and intronic portions of the gene encoding the microtubule-associated protein, tau. Even subtle changes In tau binding or in the relative concentration of tau isoforms appear to be sufficient to cause this debilitating and fatal disease. CONCLUSION- The protean clinical manifestations of FTDP-17 present a challenge to clinicians. Careful scrutiny of family history, a high degree of suspicion, and postmortem examination of affected family members is critical in making an accurate diagnosis. The effect of mutations in FTDP-17 suggests that tau could be pathogenic in Alzheimer's disease and other neurodegenerative disorders with neurofibrillary tangles.