# Huntington's Disease and Huntington's Disease‐like 2 (HDL2) in Martinique

## TL;DR

This study examines the prevalence and characteristics of Huntington's Disease and HDL2 in Martinique, finding similarities in their progression and genetic patterns.

## Contribution

The study reports the most extensive HDL2 pedigree to date and provides insights into the clinical and genetic features of HDL2 in a specific population.

## Key findings

- Combined HD and HDL2 prevalence in Martinique is 7.77/100,000.
- HDL2 cases were predominantly male and showed progressive motor and functional decline similar to HD.
- Inter- and intra-familial clinical and genetic heterogeneity was observed in both diseases.

## Abstract

Huntington's Disease‐like 2 (HDL2), caused by a CAG repeat expansion in JPH3, closely resembles HD. All reported HDL2 patients to date have some African ancestry. While both disorders exist in the Caribbean, their relative frequency and clinical characteristics remain largely unknown.

To characterize HD and HDL2 patients in Martinique.

We retrospectively analyzed all HD and HDL2 patients evaluated over 20 years at a single neurology center in Martinique, collecting longitudinal clinical features, UHDRS scores, and repeat lengths.

In Martinique, combined HD and HDL2 minimum prevalence was 7.77/100,000. We ascertained 24 HD individuals, from 16 pedigrees, and 18 HDL2 individuals, from two pedigrees, one being the most extensive HDL2 pedigree yet reported. Because most HDL2 patients belong to a single large pedigree, the data must be interpreted with caution as familial clustering may introduce bias. HDL2 cases were predominantly male (83% vs. 45% in HD). Motor symptoms were the most frequent initial manifestation in both. Repeat length negatively correlated with estimated onset age in both diseases. Longitudinal motor (UHDRS‐TMS) and functional capacity (UHDRS‐TFC) scores in HDL2 revealed progressive worsening similar to HD. Inter‐ and intra‐familial clinical and genetic heterogeneity was obvious in both diseases. Anticipation was not exclusively reserved to paternal transmissions in HDL2.

HDL2 is nearly as prevalent as HD in Martinique. The study reinforces the similarities between HD and HDL2 in genotype–phenotype correlation and disease course, while highlighting heterogeneity and germline instability in HDL2. Interpretation is limited by the small number of HDL2 families.