Huntington's Disease in Chile: Epidemiological and Genetic Aspects

Area of Science:

• Neurogenetics
• Neurology
• Epidemiology

Background:

• Huntington's disease (HD) is a neurodegenerative disorder caused by a CAG trinucleotide expansion in the HTT gene.
• It presents with motor, psychiatric, and cognitive symptoms, significantly impacting patients and families.
• Characterizing HD in specific populations is crucial for understanding disease prevalence and genetic factors.

Purpose of the Study:

• To report on the genetic, sociodemographic, and neuropsychiatric features of Huntington's disease patients in Chile.
• To establish the minimum prevalence of HD in Chile during the era of molecular diagnosis.
• To analyze the correlation between CAG repeat expansion and age of onset in the Chilean HD cohort.

Main Methods:

• Retrospective analysis of a prospective cohort of 103 Huntington's disease (HD) probands seen at the Center for Movement Disorders (CETRAM) in Chile (2013-2019).
• Investigation of sociodemographic data, HTT gene CAG repeat numbers (CAGR), and neuropsychiatric features.
• Pedigree analysis to identify affected relatives and individuals at genetic risk.

Main Results:

• The minimum estimated prevalence of HD in Chile was 0.72 per 100,000 inhabitants in 2019.
• The mean CAG repeat expansion (CAGR) was 47.2 ± 10.74 for the expanded allele and 17.93 ± 2.05 for the normal allele.
• A significant negative correlation was found between age of onset and CAGR of the expanded allele (r = -0.84, p < 0.0001), with juvenile cases representing 7.8%.

Conclusions:

• This is the first report detailing the genetics, motor, and neuropsychiatric characteristics of HD patients in Chile.
• The mean CAGR expansion is comparable to North American reports and higher than in Argentina.
• The minimal prevalence of HD in Chile may be lower than previously estimated, warranting further investigation.