Title:Clinical, Genetic, and Pathological Features of very Early Onset Frontotemporal
Lobe Degeneration: A Systematic Review
Volume: 19
Issue: 13
Author(s): Min Chu, Liyong Wu*, Li Liu, Haitian Nan, Deming Jiang, Yihao Wang and Pedro Rosa-Neto
Affiliation:
- Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China
Keywords:
Frontotemporal lobe degeneration, early onset, clinical features, neurogenetics, neuropathology, dementia.
Abstract:
Background: In most patients with frontotemporal lobe degeneration (FTLD), the degenerative
process begins between the ages 45 and 65 years; onset younger than 45 years is relatively rare
and considered very early onset FTLD (VEO-FTLD).
Objective: To delineate the clinical, genetic, and pathological features of VEO-FTLD.
Methods: A systematic literature review was carried out in PubMed and Embase from inception to
September 2021. Patients diagnosed with definite FTLD with onset before age 45 years were included.
Patients lacking detailed clinical data or both genetic and neuropathological data were excluded.
Phenotypic, genotypic, and pathological data were extracted for further analyses.
Results: Data from 110 patients with VEO-FTLD, reported in a cumulative 70 publications, were included.
Age of onset was 35.09 ± 7.04 (14-44) years. Sixty-seven patients were reported age at death
of 42.12 ± 7.26 (24–58) years, with a disease course lasting 8.13 ± 4.69 (1–20) years. Behavioural
variant frontotemporal dementia (104/110, 94.5%) was the most common clinical subtype, often manifesting
as disinhibition (81.8%) and apathy (80.9%), and frequently accompanied by a cognitive deficit
(90.9%) and parkinsonism (37.3%). Frequency of familial aggregation was high (familial vs. sporadic,
73/37, 66.4%); most patients carried MAPT gene mutations (72.9% in familial, 40% in sporadic),
followed by C9 (18.8% in familial, 10% in sporadic), TARDBP (2.1% in familial), and VCP
(2.1% in familial). The most common neuropathology subtype was tau (43.5%), followed by ubiquitin-
positive (24.6%), FUS (20.3%), and TDP 43 (2.9%).
Conclusion: VEO-FTLD may have unique clinical, genetic, and neuropathological markers and
should be considered in young patients with psycho-behavioral symptoms.
