Non-HD-Chorea: An Expanding Universe

Resumo

The main aim of this article is to provide a practical diagnostic approach to phenocopies of Huntington disease (HD). These are defined as conditions characterized by a phenotype similar to HD but with no pathogenic repeat expansion in the HTT gene. Their frequency ranges from 2% to 40% depending on ethnicity and geographic location. The most frequent genetic causes are Huntington Disease-like 2/JHP3, followed by spinocerebellar ataxia genes (SCA17/TBP, SCA12/PPP2R2B and SCA3/ATXN3, CACNA1A), and frontotemporal dementia genes (C9orf72, and VCP). There is current recognition that a growing number of acquired causes can mimic HD. Autoimmune causes such as primary antiphospholipid syndrome, paraneoplastic chorea, and anti-IGLON5 antibodies, as well as stroke, and diabetes mellitus type 2 complications are the leading acquired causes of HD phenocopies. Finally, we provide practical recommendations on how to approach HD phenocopies considering age at onset, ethnicity, and geographic location of individuals.