Expanding the Spectrum of Movement Disorders Associated With <i>C9orf72</i> Hexanucleotide Expansions
Carlos Estevez‐Fraga, Francesca Magrinelli, Davina Hensman Moss, Eoin Mulroy, Giulia Di Lazzaro, Anna Latorre, Melissa Mackenzie, Henry Houlden, Sarah J. Tabrizi, Kailash P. Bhatia
Abstract
<h3>Objective</h3> Hexanucleotide repeat expansions (HREs) in <i>C9orf72</i> are a major cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). We aimed to determine the frequency and phenomenology of movement disorders (MD) in carriers of HRE in <i>C9orf72</i> through a retrospective review of patients9 medical records. <h3>Methods</h3> We retrospectively reviewed the clinical records of patients carrying a <i>C9orf72</i> HRE in the pathogenic range and compared the characteristics of patients with and without MD. <h3>Results</h3> Seventeen of 40 patients with a <i>C9orf72</i> HRE had a documented MD. In 6 of 17, MD were the presenting symptom, and in 2 of 17, MD were the sole manifestation of the disease. FTD was present in 13 of 17 patients, ALS in 5 of 17 patients, and 2 of 17 patients did not develop FTD or ALS. Thirteen of 17 patients had more than one MD. The most common MD were parkinsonism and tremor (resembling essential tremor syndrome), each one present in 11 of 17 patients. Distal, stimulus-sensitive upper limbs myoclonus was present in 6 of 17 patients and cervical dystonia in 5 of 17 patients. Chorea was present in 5 of 17 patients, 4 of whom showed marked orofacial dyskinesias. The most frequent MD combination was tremor and parkinsonism, observed in 8 of 17 patients, 5 of whom also had myoclonus. <i>C9orf72</i> patients without MD had shorter follow-up times and higher proportion of ALS, although these results did not survive the correction for multiple comparisons. <h3>Conclusions</h3> MD are frequent in <i>C9orf72</i>. They may precede signs of ALS or FTD, or even be present in isolation. Parkinsonism, tremor, and myoclonus are most commonly observed.