Abnormal C9orf72 frontotemporal dementia behavioural variant presenting as manic psychosis

To the Editor

Frontotemporal dementia (FTD) is caused by mutations in a variety of protein encoding genes: microtubule-associated protein tau (MAPT), progranulin (GRN), valosin-containing protein (VCP) and charged multivesicular body protein 2B (CHMP2B; Rademakers et al., 2012). In 2011, families with a combination of FTD and amyotrophic lateral sclerosis (ALS) were found to have an expanded hexanucleotide repeat – GGGGCC (G4C2) – in the noncoding region of the chromosome 9 open reading frame 72, known as the C9orf72 gene (DeJesus-Hernandez et al., 2011).

We present a case of a 67-year-old man with FTD behavioural variant (FTDbv) caused by abnormal C9orf72 gene. He had no previous psychiatric history, but a family history of frontal dementia (mother) and mood disorder (father) requiring treatment with electroconvulsive therapy. He was a highly accomplished lawyer with an unblemished record. The first sign of behaviour change was 18 months prior to presentation when he was found guilty of professional misconduct (misappropriating money, falsifying documents, lying to investigators) while acting as executor to a deceased estate. He was disqualified from practising law for 8 months. One week prior to presentation, he was admitted to a private hospital with manic symptoms and psychosis. Biochemical tests including autoimmune screen, heavy metals, ceruloplasmin and syphilis serology were unremarkable. Magnetic resonance imaging (MRI) of the brain showed diffuse cerebral tissue loss predominantly in the frontotemporal lobes. Mini Mental State Examination was 22/30. On presentation to our service, he was fatuous and suspicious, with delusions of self-reference and grandiosity. He scored 76/100 on Addenbrooke’s Cognitive Examination and 10/18 on Frontal Assessment Battery. Neuropsychological assessment detailed prominent and severe executive dysfunction and impaired new learning.

Further enquiry revealed a family history of motor neuron disease (maternal uncle and cousin). Initial FDG-PET (18-Fluoro-deoxyglucose positron emission tomography) scan was suggestive of FTDbv but inconclusive, with reduction in metabolism in the anterolateral frontal lobes and anterior cingulate gyrus. During the next 8 months, he became more disinhibited, apathetic, and displayed verbal and manual stereotypies. He was treated privately for mood disorder. Follow-up FDG-PET 10 months post presentation showed progression of hypometabolism in bilateral frontotemporal lobes and anterior cingulate gyrus. Genetic testing confirmed abnormal C9orf72 gene, with one normal allele and one expanded allele with >145 G4C2 repeats.

This case highlights the fact that FTDbv C9ORF72 carriers are more likely than FTDbv non-carriers to have relatives with ALS and psychiatric illness, and to present initially with psychosis, which may lead to incomplete or delayed diagnosis (Devenney et al., 2014).