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. 2019 Mar 12;6(4):302-311.
doi: 10.1002/mdc3.12742. eCollection 2019 Apr.

Comparison of the Huntington's Disease like 2 and Huntington's Disease Clinical Phenotypes

David G Anderson  1   2 , Aline Ferreira-Correia  3 , Filipe B Rodrigues  4   5   6 , N Ahmad Aziz  7 , Jonathan Carr  8 , Edward J Wild  4 , Russell L Margolis  9 , Amanda Krause  2
Affiliations

Comparison of the Huntington's Disease like 2 and Huntington's Disease Clinical Phenotypes

David G Anderson et al. Mov Disord Clin Pract. .

Abstract

Background: Huntington's disease like 2 (HDL2) is the most common Huntington's disease (HD) phenocopy in many countries and described as the phenocopy with the greatest resemblance to HD. The current clinical description of HDL2 is based on retrospective data. It is unknown whether HDL2 has clinical features that distinguish it from HD.

Objective: To describe the HDL2 phenotype and compare it to HD systematically.

Methods: A blinded cross-sectional design was used to compare the HDL2 (n = 15) and HD (n = 13) phenotypes. African ancestry participants underwent assessments, including the Unified Huntington's Disease Rating Scale (UHDRS). The UHDRS motor component was video recorded and evaluated by blinded experts and the inter-rater reliability calculated.

Results: Both groups were homogeneous in terms of demographics and disease characteristics. However, HDL2 patients presented three years earlier with more prominent dysarthria and dystonia. Raters could not distinguish between the two diseases with a high level of agreement. No significant differences in the TMS between HDL2 and HD were found. In both disorders, disease duration correlated with motor scores, with the exception of chorea. Psychiatric and cognitive scores were not significantly different between the groups.

Conclusions: The HDL2 phenotype is similar to HD and is initially characterized by dementia, chorea, and oculomotor abnormalities, progressing to a rigid and bradykinetic state, suggesting the UHDRS is useful to monitor disease progression in HDL2. Although HDL2 patients scored higher on some UHDRS domains, this did not differentiate between the two diseases; it may however be emerging evidence of HDL2 having a more severe clinical phenotype.

Keywords: Huntington's disease; Huntington's disease like 2; Huntington's disease phenocopy; chorea; phenotype.

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Figures

Figure 1
Figure 1
Distribution of Huntington's disease like 2 and Huntington's disease patients. Map of Southern Africa showing the distribution of Huntington's disease like 2 and Huntington's disease patients. Abbreviations: HD, Huntington's disease; HDL2, Huntington's disease like 2; n = number of participants.
Figure 2
Figure 2
Age of disease onset vs. abnormal repeat length. Scatterplot showing inverse relationship between age of onset and abnormal triplet repeat length for both HDL2 and HD. Abbreviations: HD, Huntington's disease; HDL2, Huntington's disease like 2.
Figure 3
Figure 3
Scatterplots for Unified Huntington's Disease Rating Scale Total Motor Score and sub‐scores vs. duration of disease. Scatterplots demonstrating the TMS and some sub‐scores from the UHDRS. (A) Total Motor Score (B) Ocular Score (C) Dysarthria Score (D) Rigidity Score (E) Dystonia (F) Chorea (G) Bradykinesia (H) Gait. Abbreviations: HD, Huntington's Disease; HDL2, Huntington's Disease like 2; UHDRS TMS, Unified Huntington's Disease Rating Scale Total Motor Score; y, year.
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References

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