Objective: Objective

To determine if eye movements are preserved in Huntington Disease-Like 2 (HDL2) and if this can be used to differentiate HDL2 from Huntington Disease (HD).

Background: Background

Preserved ocular motor function has been observed in HDL2 and  suggested as a potential differentiating sign from HD[1]. Eye movements were reported as normal in 7 of 18 cases reported in the literature up to the end of 2015. Abnormal eye movements are a cardinal and early feature of HD. Normal eye movements in HDL2 would predict sparing of the brainstem in HDL2, as has been has been demonstrated in 5 cases histopathologically. South Africa has the highest recorded number of HDL2 cases, making it the ideal setting to prospectively study HDL2[2]

Methods: Methods

Twenty-two patients (13 HD and 9 HDL2) have been studied through the Division of Human Genetics, National Health Laboratory Service (NHLS) & The University of the Witwatersrand in Johannesburg. The 22 cases were tested for HD and HDL2 through the Division. All have African ancestry and were enrolled over 18 months. Cases underwent a UHDRS which was videoed and the first 6 items (horizontal and vertical-ocular pursuit, saccade initiation and saccade velocity) of the motor component were then scored by a blinded examiner.

Results: Results

The mean age for the HDL2 group was 51.3 years (SD=8.22), the mean disease duration was 6.00 years (SD=2.55) and median expanded JPH3 repeat length was 44 with a mean of 45.89 (SD=2.76). In the HD group the mean age was 46.77 years (SD=13.22), the mean disease duration was 7.69 years (SD=2.55) and median expanded HTT repeat length was 46 with a mean of 45.00 (SD=3.27). All HDL2 and HD patients had abnormal eye movements. There was no significant difference in the total score between the two diseases or in any median sub-score parameters of ocular pursuit, saccade initiation or saccade velocity. There was also no association between the individual parameters when compared to age, repeat length or disease duration in each disease. 

Conclusions: Conclusions

All patients with HDL2 had abnormal eye signs that were indistinguishable from HD patients. Although this is a small sample, this is the largest prospective/systematic study of HDL2 patients. This would suggest that eye signs are similar in HD and HDL2 adding further evidence of common pathological processes in the diseases.

References: References

1   Margolis RL, O’Hearn E, Rosenblatt A, et al. A Disorder Similar to Huntington’s Disease Is Associated with a Novel CAG Repeat Expansion. Annals of neurology 2001;50:373–80. doi:10.1002/ana.1124

2   Krause A, Mitchell C, Essop F, 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 2015;168:573–85. doi:10.1002/ajmg.b.32332

« Back to 2017 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/eye-movements-in-huntington-disease-like-2/