Inheritance of frontotemporal dementia

Background: Previous studies of families with frontotemporal dementia (FTD) support an autosomal dominant inheritance pattern, but most studies have d escribed genetic transmission in individual families specifically selected for the presence of multiple affected individuals. Objective: To investigate the familial presentation and inheritance of FTD and related disorders among a large group of FTD index cases unselected for family history of dementia. Design and Setting: We interviewed family members and reviewed medical reco rds and autopsy reports at a university hospital and a university-affiliate d hospital to determine the frequency of familial FTD and the most likely m ode of inheritance. Characteristic families with the disorder are described , along with the history, clinical findings, and neuroimaging results in af fected members of these families. Patients and Participants: The 42 index cases of FTD had a mean age of onse t of 56.1 years (range, 40-69 years). Of these patients, 21 (50%) were wome n. All but one of the patients were white. Participants included male and f emale spouses and children of the index cases. Results: Of 42 FTD cases, 19 (45%) had at least 1 other family member with an FTD spectrum disorder and were considered familial cases. The majority ( 17 [89%]) of familial FTD cases showed a pattern consistent with dominant i nheritance. If depression is excluded, familial cases decrease from 19 (45% ) to 17 (40%), of which 15 (88%) showed a dominant transmission pattern. Th e initial presentations in the nonindex familial cases varied but most freq uently consisted of personality and behavioral changes that preceded cognit ive impairment (19 [43%]), followed by psychiatric illness (14 [33%]), deme ntia without behavioral change (5 [11%]), amyotrophic lateral sclerosis (5 [11%]), and parkinsonism (2 [5%]). Two of the affected nonindex cases had d ual presenting diagnoses. The average age of onset was 56.1 years and did n ot differ significantly between familial and nonfamilial cases. Onset of FT D-related symptoms occurred after the age of 65 years in only 4 (10%) of 42 index cases and 3 (5%) of 60 affected relatives. Conclusions: Familial FTD is usually inherited in an autosomal dominant pat tern. The initial onset is insidious, often consisting of mood and behavior al changes occurring in presenile years that are often erroneously attribut ed to other nonneurologic causes. Although the precise incidence of FTD in North America is not known, it is one of the most common presenile dementia s.