Early Onset Behavioral Variant Frontotemporal Dementia due to the C9ORF72 Hexanucleotide Repeat Expansion: Psychiatric Clinical Presentations

Abstract

A hexanucleotide repeat expansion in the first intron of C9ORF72 has been shown to be responsible for a high number of familial cases of amyotrophic lateral sclerosis or frontotemporal lobar degeneration with or without concomitant motor neuron disease phenotype and TDP-43 based pathology. Here, we report on three cases carrying the hexanucleotide repeat expansion with an atypical presentation consisting in the development of psychiatric symptoms. Patient #1, a 53 year old man with positive family history for dementia, presented with mood deflection, characterized by apathy, social withdraw, and irritability in the last two years. He was diagnosed with "mild cognitive impairment due to depressive syndrome" six months later and subsequently with Alzheimer's disease. Patient #2, a woman with positive family history for dementia, developed behavioral disturbances, aggressiveness, and swearing at 57 years of age. Patient #3 presented, in the absence of brain atrophy, with mystical delirium with auditory hallucinations at 44 years of age, and did not present neurological symptoms over a 7-year follow up. The description of these cases underlines that the hexanucleotide repeat expansion in chromosome 9 could be associated with early onset psychiatric presentations.

C9ORF72 G4C2-repeat expansion and frontotemporal dementia first reported case in Argentina

“…These findings were replicated by other authors (Arighi, Fumagalli, & Jacini et al, 2012;Kertesz et al, 2013). Furthermore, psychosis as the only initial symptom in G4C2 expansion carriers had also been described (Arighi et al, 2012). Secondly, the patient showed partial awareness of the abnormality of her symptoms (Arighi et al, 2012), being also repeatedly conscious of her misbehavior and showing anxiety and regret when realizing what is happening; this feature is atypical for bvFTD, which in general has a profound anosognosia ( core feature of this entity.…”

Inflammatory molecules in Frontotemporal Dementia: Cerebrospinal fluid signature of progranulin mutation carriers

“…Notably, CSF Abeta and tau/Ptau evaluation was carried out to exclude AD, as in the last few years many patients carrying mutations having had an onset with memory disturbances, which are actually associated with AD rather than FTLD, have been described (Arighi et al, 2012;Carecchio et al, 2009;Galimberti et al, 2013).…”

Psychiatric Symptoms in Frontotemporal Dementia: Epidemiology, Phenotypes, and Differential Diagnosis

“…As previously stated, bvFTD onset can resemble, mimicking or being misdiagnosed with, symptoms of different psychiatric disorders, which do not only belong to the schizophrenic/psychotic spectrum but also to the depressive, bipolar, obsessivecompulsive and impulse-control spectrum disorders (71,87,89,96,97).…”