Clinical and genetic characteristics of patients with very early onset frontotemporal dementia

Abstract

AbstractBackgroundFrontotemporal dementia (FTD) spectrum disorders may occur in patients who are under 45 years old, often posing a diagnostic challenge, yet little is known about the clinical presentation and underlying genetic causes in this age group.MethodAs part of a prospective study focused on FTD, 780 participants met the research criteria for an FTD spectrum disorder between 2002‐2021. Of these, 40 patients (5.1%, 18 females) presented with age at onset < 45 years and constituted the very early onset frontotemporal dementia (VEO‐FTD) group. Their research records were reviewed to delineate their clinical characteristics. A panel of 40 dementia and amyotrophic lateral sclerosis‐associated genes was screened for pathogenic genetic variation using standardized methods.ResultBehavioral variant of frontotemporal dementia was disproportionally represented in the VEO‐FTD group (n = 35, 87.5%) suggesting selective vulnerability of the social‐emotional brain networks to frontotemporal lobar degeneration underlying neuropathologies in this age range. The median age at first symptom was 39 (interquartile range (IQR) = 32‐42.2) years, and the median diagnostic delay from symptom onset was 4 (IQR 2‐8.25) years. Initial misdiagnosis with a primary psychiatric disorder was prevalent, occurring in 17 (42.3%) of patients, and was diverse including mood, psychotic, anxiety, and addictive disorders. In five patients (12.5%), positive psychotic symptoms were reported, mostly as a presenting symptom or arising within a year from the first symptom. Among the VEO‐FTD patients, 18 (45%) carried C9orf72, MAPT or UBQLN2 pathogenic variants.ConclusionFTD spectrum disorders may occur under the age of 45 and are often misdiagnosed. The high prevalence of monogenic causes in this age group warrants timely genetic testing, especially in the era of emerging gene‐specific therapies.