TBK1 mutation and its role in frontotemporal dementia and amyotrophic lateral sclerosis in Brazilian families.

Abstract

Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are progressive neurodegenerative diseases with unclear etiology. Mutations in the TBK1 gene are associated with an increased risk of both FTD and ALS, presenting a diverse phenotype that includes the behavioral variant of FTD, primary progressive aphasia, and pure ALS. This mutation is rare, and to date, only one case report on TBK1-related clinical manifestations has been published in Brazil.

Objective: To investigate the association between TBK1 gene mutations and the clinical manifestations of FTD and ALS in a Brazilian family, documenting the clinical history and disease progression of three first-degree relatives. Additionally, to conduct a literature review to better understand the impact of this mutation and its implications for neurological practice.

Methods: Clinical data were collected from three patients in the same family who were receiving care at Dom Pedro II Geriatric Hospital and Central Hospital of the Irmandade da Santa Casa de Misericordia de São Paulo, including information on clinical symptoms, disease progression, and complementary exams - particularly genetic testing to detect and confirm the diagnosis. A detailed analysis of the existing literature on the disease was also conducted to better understand the implications of this mutation.

Results: Three siblings affected by the TBK1 gene mutation were documented, with a unique family history suggesting that this genetic alteration has affected the lineage for several generations.

Conclusion: Although rare, frontotemporal dementia with accompanying motor deficits is of significant relevance to neurologists due to its poor prognosis and the potential familial impact on descendants.