[Genetics of frontotemporal dementia]

Area of Science:

• Neuroscience
• Genetics
• Psychiatry

Background:

• Frontotemporal dementia (FTD) is a neurodegenerative disorder characterized by behavioral and emotional changes.
• Its presentation often leads to initial psychiatric evaluation.
• Genetic factors play a significant role in a subset of FTD cases.

Purpose of the Study:

• To provide a comprehensive overview of the genetic underpinnings of FTD.
• To offer clinical recommendations for identifying and managing genetic FTD.
• To highlight the importance of genetic testing in specific patient populations.

Main Methods:

• A thorough review of the international scientific literature on FTD genetics.
• Analysis of studies detailing the clinical presentation and genetic mutations associated with FTD.
• Synthesis of findings to inform clinical practice.

Main Results:

• Autosomal dominant hereditary patterns are observed in 10-25% of FTD cases.
• Genetic FTD exhibits significant clinical heterogeneity.
• The C9ORF72 mutation is a notable genetic factor, potentially causing psychiatric manifestations, slow disease progression, and association with Amyotrophic Lateral Sclerosis (ALS).

Conclusions:

• A detailed family history, encompassing dementia, ALS, and psychiatric disorders, is crucial for late-onset psychiatric conditions.
• Genetic testing, specifically for the C9ORF72 hexanucleotide repeat length, should be considered for undetermined neuropsychiatric disorders, irrespective of family history.
• Early consideration of genetic testing can aid in accurate diagnosis and management of FTD.