Objective: To describe the clinical phenotypes of Huntington’s disease-like 2 patients in a referral movement disorders (MD) center in Brazil.

Background: Huntington’s disease-like 2 (HDL2) seems to be restrict to families with African heritage. There is evidence for a founder mutation and support of a common African origin for all HDL2 patients¹. It may present with chorea, dystonia, parkinsonism, and neuropsychiatric abnormalities, and cannot be differentiated from Huntington’s disease (HD) clinically². The diagnosis of HDL2 is based on clinical evaluation, family history and genetic testing with the detection of an expansion of 40 or more CTG trinucleotide repeats in the Junctophilin gene (JPH3) ². Previous studies with Brazilian patients showed that 4-10% of patients with HD clinical phenotype had in fact HDL2 ³.

Method: We performed a retrospective review including clinical, demographic and genetic data from 9 patients with confirmed genetic diagnosis of HDL2 followed at a MD center in Brazil.

Results: From 9 patients evaluated, 77% were male. 3 patients declared themselves as white, 3 as brown, 1 as black, and 2 as “other” race. The mean age of symptom onset was 39.1 years old. CTG expansions ranged from 44 up to 57, with a mean of 48.7 repetitions. Regarding the initial symptom, 5 patients (55,5%) had chorea, 2 had neuropsychiatric abnormalities and 2 had parkinsonism. Patients with parkinsonism present the largest expansions (54 and 57). 8 out of the 9 patients had a positive family history, and 1 had an unknown family history.

Conclusion: HDL2 is a well-known phenocopy of HD. Although rare, it is probably underdiagnosed in our country. Genetic testing availability is still an important issue. Chorea presentation is more common, but parkinsonism is also possible. Family history is often positive or unknown. Negative family history should be reevaluated. African ancestry is usually found in history, and here we have to highlight the difference between race (self-ascribed) and genetic ancestry. This case series shows different HDL2 phenotypes and also the need for remembering HDL2 diagnosis in cases where HD genetic test turns out to be normal, especially in a country like Brazil with such a strong African ancestrality. By identifying those patients, we will be one step ahead of finding a disease-modifying treatment.

References: 1. Krause, A. et al. Junctophilin 3 (JPH3) expansion mutations causing Huntington disease like 2 (HDL2) are common in South African patients with African ancestry and a Huntington disease phenotype. Am. J. Med. Genet. B Neuropsychiatr. Genet. 168, 573–585 (2015).
2. Anderson, D. G., Krause, A. & Margolis, R. L. Huntington Disease-Like 2. (University of Washington, Seattle, 2019).
3. Walker, R. H. et al. Huntington’s disease-like disorders in Latin America and the Caribbean. Parkinsonism Relat. Disord. 53, 10–20 (2018).

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MDS Abstracts - https://www.mdsabstracts.org/abstract/huntingtons-disease-like-2-phenotypes-a-case-series-from-a-brazilian-referral-center/