Behavioral Variant Frontotemporal Dementia With C9orf72 Intermediate Repeat Expansion : A case report

Area of Science:

• Genetics
• Neuroscience
• Neurology

Background:

• Hexanucleotide repeat expansions in the C9orf72 gene are the leading genetic cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS).
• The exact number of repeats defining a pathogenic expansion, particularly in the intermediate range (30 to >60 repeats), remains debated.
• This uncertainty impacts genetic diagnosis and counseling for patients and families.

Purpose of the Study:

• To report a rare case of behavioral variant frontotemporal dementia (bvFTD) associated with an intermediate-length C9orf72 repeat expansion.
• To contribute clinical evidence to the ongoing discussion regarding the pathogenicity of C9orf72 alleles within the intermediate repeat range.
• To highlight the clinical presentation and neuroimaging findings in a patient with this specific genetic profile.

Main Methods:

• Case report of a patient diagnosed with bvFTD.
• Genetic analysis to identify and quantify the C9orf72 repeat expansion.
• Neuropsychological assessment to evaluate cognitive and behavioral deficits.
• Neuroimaging studies (MRI/PET) to assess brain structure and function.

Main Results:

• The patient presented with a C9orf72 repeat expansion of 49 units, falling within the intermediate-length range.
• Clinical manifestations included progressive neuropsychiatric decline, emotional blunting, and memory impairment.
• Neuroimaging revealed bilateral temporal and hippocampal atrophy and reduced glucose metabolism in specific brain regions.

Conclusions:

• This case provides critical clinical data supporting the potential pathogenicity of intermediate-length C9orf72 repeat expansions.
• The findings underscore the importance of considering intermediate alleles in the genetic diagnosis of FTD and ALS.
• Further research is warranted to definitively establish the pathogenic threshold for C9orf72 repeat expansions.