Early onset frontotemporal dementia with psychiatric presentation due to the C9ORF72 hexanucleotide repeat expansion: a case report

Abstract

BackgroundFrontotemporal dementia (FTD) may present with psychiatric symptoms, usually together with neurological ones and in cases with a family history of dementia. We describe the case of an FTD behavioural variant with a psychiatric presentation and a normal neurological examination, due to a C9Orf72 gene mutation.Case presentationThe patient was a 57 years-old Caucasian woman with a recent onset of bizarre behaviours and mystic delusions. She had a negative clinical history for previous psychiatric disorders and treatments and this was her first admission to a Psychiatry Ward. A careful assessment was performed including, beyond psychiatric evaluation, the following: blood sampling, neurological examination (including electroencephalogram, electroencephalogram with zygomatic electrodes, Positron Emission Tomography, Cerebrospinal Fluid Analysis), carotid artery Doppler ultrasound, brain Magnetic Resonance Imaging – angio Magnetic Resonance Imaging. Blood sampling for the genetic assessment of mutations associated to primary dementias was performed as well: the genes investigated were FUS, C9Orf72, PSEN-1, PSEN-2.ConclusionsSerological tests were negative, neurological examination was normal, instrumental examinations showed theta waves in the posterior temporal areas bilaterally and frontotemporal cortical atrophy bilaterally. The genetic assessment of mutations associated revealed she carried a GGGGCC hexanucleotide repeat expansion (at least 80 repeats) in C9Orf72 intron 1. Patients carrying the C9Orf72 mutation are likely to receive a psychiatric diagnosis (mainly mood disorder or schizophrenia) prior to correct diagnosis; this may be particularly problematic for those patients with no neurological signs to orientate diagnosis. Understanding the manner in which such FTD variant may present as a psychiatric syndrome, with a negative neurological examination, is essential to provide the best treatment for patients, as soon as possible, especially when the behavioural anomalies interfere with their care.

Psychotic Symptoms in Frontotemporal Dementia

“…A few cases in the literature have reported some improvements in symptoms when antipsychotics were initiated [53][54][55]. Patients with FTD are sensitive to the side effects of antipsychotics, with extrapyramidal symptoms occurring in 33 % and severe in 21 % [56].…”

C9orf72 repeat expansions that cause frontotemporal dementia are detectable among patients with psychosis

“…Among UK biopsy-confirmed individuals with FTD, 5/17 individuals had previously been diagnosed with a psychotic illness (Shinagawa et al, 2014 and Velakoulis et al, 2009) It is thus possible that patients with early onset FTD are misdiagnosed with psychoses such as schizophrenia (SZ), or individuals with SZ may later be diagnosed with FTD. Indeed, C9orf72 mutations have been reported in individual SZ case reports (Gramaglia et al, 2014). A pathogenic repeat expansion was reported in 0.67% of Italian patients with SZ (Galimberti et al, 2014); the low frequency may explain why the expansions were not detected in other studies (Huey et al, 2013, Yoshino et al, 2014 and Fahey et al, 2014).…”

Behavioral variant frontotemporal dementia in patients with previous severe mental illness: a systematic and critical review

“…On LILACS, none of the nine retrieved met the requirements. Therefore, 42 articles were selected, of which 10 were cohort studies 15,16,17,18,19,20,21,22,23,24 , three were case-control studies 25,26,27 , 12 were case repo rts 28,29,30,31,32,33,34,35,36,37,38,39 and 17 other studies were cross-sectional surveys 6,7,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54 .…”

“…Cross-sectional studies comparing the neurocognitive profile between bvFTD and psychiatric disorders mostly found no remarkable differences 44,45,47,53 , or pointed to less severe deficits in bvFTD 49,55 . Lastly, there were several case reports that established a definite FTLD diagnosis, through genetic or histopathological examination, in patients with previous diagnoses or clinical histories compatible with BD/SCZ/SZA or atypical psychiatric symptoms 28,29,30,31,32,33,34,35,36,37,38,39 .…”