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Updated: Jun 9, 2025

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Published on: August 24, 2013
Huntington's disease phenocopy syndromes revisited: a clinical comparison and next-generation sequencing exploration
Carolin Anna Maria Koriath1,2, Fernando Guntoro2, Penelope Norsworthy2
1LMU University Hospital, Department of Psychiatry and Psychotherapie, Ludwig Maximilian University of Munich, Munchen, Bayern, Germany.
Background:
Genetic testing for Huntington's disease (HD) was initially usually positive but more recently the negative rate has increased: patients with negative HD tests are described as having HD phenocopy syndromes (HDPC). This study examines their clinical characteristics and investigates the genetic causes of HDPC.
Methods:
Clinical data from neurogenetics clinics and HDPC gene-panel data were analysed. Additionally, a subset of 50 patients with HDPC underwent whole-genome sequencing (WGS) analysed via Expansion Hunter and Ingenuity Variant Analysis.
Results:
HDPC prevalence was estimated at 2.3-2.9 per 100 000. No clinical discriminators between patients with HD and HDPC could be identified. In the gene-panel data, deleterious variants and potentially deleterious variants were over-represented in cases versus controls. WGS analysis identified one ATXN1 expansion in a patient with HDPC.
Conclusions:
The HDPC phenotype is consistent with HD, but the genotype is distinct. Both established deleterious variants and novel potentially deleterious variants in genes related to neurodegeneration contribute to HDPC.
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