Young-onset frontotemporal dementia with FUS pathology

Area of Science:

• Neurology
• Neuroscience
• Pathology

Background:

• Frontotemporal dementia (FTD) is a neurodegenerative disorder typically affecting individuals under 50.
• It manifests as progressive behavioral and cognitive changes, including social withdrawal, apathy, and executive dysfunction.
• Genetic factors are implicated in some FTD cases, but sporadic forms also exist.

Purpose of the Study:

• To report a case of frontotemporal dementia (FTD) with unusual clinical presentation in a young adult.
• To investigate the underlying pathology in a patient with negative genetic testing for common FTD-associated genes.
• To emphasize the diagnostic considerations for rare causes of FTD.

Main Methods:

• Clinical case presentation of a 44-year-old male with progressive neuropsychiatric symptoms.
• Neuropsychological testing to assess cognitive function, revealing severe executive dysfunction.
• Magnetic Resonance (MR) imaging of the brain to identify structural changes, showing frontal atrophy.
• Genetic testing for FTD-associated genes (MAPT, GRN, C9orf72) and subsequent pathological examination.

Main Results:

• The patient exhibited social withdrawal, apathy, loss of empathy, motor stereotypies, and hyperorality.
• Brain MR scans revealed bilateral symmetrical frontal atrophy.
• Genetic testing for MAPT, GRN, and C9orf72 variants was negative.
• Pathological diagnosis confirmed frontotemporal lobar degeneration with fused-in-sarcoma (FUS) pathology.

Conclusions:

• Fused-in-sarcoma (FUS) pathology is a rare, sporadic cause of frontotemporal dementia (FTD), accounting for 5%-10% of cases.
• FTD with FUS pathology can present with very young onset and characteristic features like motor stereotypies and hyperorality.
• This case underscores the importance of considering rare pathologies in the differential diagnosis of FTD, especially in young-onset cases with atypical presentations.