C9orf72 Repeat Expansion Initially Presenting as Late-Onset Bipolar Disorder With Psychosis

Area of Science:

• Neurogenetics
• Neuropsychiatry
• Geriatric Medicine

Background:

• C9orf72 expansion is the leading genetic cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS).
• Psychiatric symptoms frequently precede FTD/ALS, but primary psychiatric diagnoses at onset are rare.
• Genetic studies of bipolar disorder seldom identify C9orf72 expansion carriers.

Observation:

• A 51-year-old woman presented with a 12-year history of mania and psychosis, initially diagnosed as bipolar disorder.
• Over time, she developed executive dysfunction, behavioral changes, and speech apraxia, indicative of bvFTD.
• Neuropathology confirmed frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP type B) and C9orf72 expansion.

Findings:

• This case highlights a rare presentation of C9orf72 expansion initially manifesting as late-onset bipolar disorder with psychotic features.
• The patient later progressed to meet diagnostic criteria for behavioral variant frontotemporal dementia (bvFTD).
• A family history revealed paternal inheritance of bipolar disorder and substance use disorder.

Implications:

• Emphasizes the need for thorough neurological examinations in patients with late-onset bipolar disorder.
• Highlights the importance of detailed family history taking in differentiating psychiatric disorders from FTD.
• Suggests genetic screening for C9orf72 expansion in specific clinical contexts to aid diagnosis and management.