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From the Dementia Research Group (Drs. Janssen, Warrington, Fox, and Rossor) and Neurogenetics Section (Drs. Morris and Wood), Institute of Neurology, Department of Neuropathology (Dr. Lantos and M.N. Khan), Institute of Psychiatry, and Departments of Neuropathology (Dr. Revesz) and Clinical Neuropsychology (Dr. Cipolotti), National Hospital for Neurology and Neurosurgery, London; and Department of Neurology (Dr. Brown), Addenbrooke’s Hospital, Cambridge, UK.
Address correspondence and reprint requests to Prof. M.N. Rossor, Dementia Research Group, Institute of Neurology, Queen Square, London WC1N 3BG, UK; e-mail: m.rossor{at}dementia.ion.ucl.ac.uk
Objective: To describe the clinical features of nine British families with neuropathologically verified frontotemporal dementia (FTD) due to the intronic tau exon 10+16 mutation.
Methods: Retrospective chart reviews of family members with FTD belonging to nine tau 10+16 mutation pedigrees in whom neuropathologic examination had been carried out. APOE genotype was determined for those patients for whom DNA was available.
Results: The median age at onset was 50 years (range 37 to 59 years; n = 30). The median age at death was 61 years (range 42 to 72 years; n = 33). The median duration of the disease was 11 years (range 3 to 22 years; n = 25) for those who have died and is 17 years (range 15 to 23 years; n = 3) for those living. The most common presenting symptom was disinhibition (n = 23). A minority presented with frontal dysexecutive symptoms, apathy, impairment of episodic memory, or depression. All of these patients subsequently developed personality and behavioral change. Memory impairment, language deficits, ritualistic behavior, hyperphagia, and hyperorality were frequent symptoms. Parkinsonism, neuroleptic sensitivity, or primitive reflexes were present in half of the patients, where these data were available. The clinical features of ALS were absent. Neuropathologic examination of 12 patients demonstrated the hallmark tau-positive neuronal and glial inclusions. APOE genotype did not account for the considerable variation in age at onset, age at death, duration of disease, or severity of estimated brain atrophy.
Conclusions: All cases fulfilled the clinical criteria for a diagnosis of FTD. Despite similar clinical phenotypes, there was considerable variation in age at onset and duration of disease both between and within families, suggesting the presence of an effect due to other genetic or environmental factors.
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