Huntington's disease-like 2 patients' profile in a Brazilian cohort

Huntington disease-like 2 (HDL2) is an autosomal dominant disorder caused by an abnormal CAG/CTG repeat in exon 2A of junctophilin-3. This is the most common Huntington's Disease phenocopy and is characterized by psychiatric, cognitive, and movement disorders. This study aimed to describe the clinical phenotype of HDL2 patients in Brazil and compare the findings with those in the literature.

This was a descriptive, observational study with a cross-sectional and retrospective component that evaluated 33 genetically confirmed HDL2 patients. Clinical data were collected using the Unified Huntington's Disease Rating Scale (UHDRS) and additional scales assessing sleep, mood, and cognition.

The sample had a balanced gender distribution and was predominantly comprised of white individuals. Median disease duration was 11 years, median age at diagnosis was 44 years, and CAG repeats were 47. On the non-motor scales, the median scores were 33 points for fatigue, 31 points for apathy, and 18 points for depression. A significant negative correlation was observed between CAG repeat length and age at symptom onset (r = -0.76, p = 0.002). The median diagnosis delay was 4.5 years.

While some findings, such as sex ratio and median CAG repeat length, were consistent with those of previous cohorts, this Brazilian sample exhibited longer diagnostic delays, an older age at assessment, and more severe motor scores. However, due to the small sample size, the results should be interpreted cautiously. Larger studies are needed to confirm these associations.