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Título

Very early-onset Behavioral variant Frontotemporal Dementia associated with FUS gene identified variant: a case report

RESUMO

Case Report
A 24 year-old male developed progressive neuropsychiatric symptoms following a mild depressive episode, with compulsive behavior, hyperorality, disinhibition and, finally, psychotic symptoms such as delusions and psychomotor agitation, leading to a psychiatric hospitalization nearly 10 months after symptom onset. The patient was initially diagnosed with schizophrenia and received several treatment attempts, including neuroleptics, SSRIs, electroconvulsive therapy and empiric high-dose corticosteroids, all of which were ineffective. He was discharged after 6 months.
The patient progressed with severe cognitive and functional decline within months. At 26 years old, he was referred to our outpatient clinic. On examination, he was globally aphasic and only vocalized a repetitive grunt. He had frontal release signs, mild generalized muscular atrophy and paratonia. Of note, he did not have motor neuron disease.
The patient had 11 years of schooling and normal childhood development. He had no history of CNS infections or trauma, nor previous psychiatric disorders. Family history included a paternal uncle with schizophrenia.
Extensive investigation ruled out systemic diseases. Neuroimaging performed 1-2 years after symptom onset showed severe atrophy in the hippocampus and head of the caudate bilaterally. Genetic testing identified a variant of uncertain significance (VUS) in the FUS gene: p.Gly229_Gly231dup.

Discussion:
This is a case of very early-onset behavioral variant frontotemporal degeneration (bvFTD) clinical phenotype with an unusual rapidly progressive course. The clinical history and neuroimaging support a hypothesis of FUS pathology, which might be related to the found variant. The fact that the same VUS was found in the patient's asymptomatic 58 year-old father raises uncertainty for establishing this relation, although most FUS gene mutations show incomplete penetrance. Importantly, the identical VUS has been reported with essential tremor and ALS. Other FUS gene variants have been reported, but without pathological confirmation. If neuropathology demonstrates FUS protein deposition, this could be the first case of FUS mutation potentially causing FTLD-FUS pathology.

Final Commentary:
FTLD-FUS pathology must be suspected in sporadic, early-onset and rapidly progressive bvFTD. The found VUS could represent a novel FUS gene mutation related to bvFTD, although additional evidence is needed to determine its pathogenicity.

Palavras Chave

bvFTD, genetic panel, FTLD-FUS, early-onset dementia, VUS, genetic panel

Área

Neurologia Cognitiva E Do Envelhecimento