Objective: To formally characterize the evolving spectrum of movement disorders associated with chromosome 22q11.2 deletion syndrome

Background: Emerging evidence suggests that a wide range of movement disorders occur in 22q11.2 deletion syndrome (22q11.2DS). However, formal phenotypic characterization of the spectrum of these problems is largely lacking.

Method: We conducted a retrospective study of 31 adults (mean ± SD age: 45.9 ± 13.0 years) with molecularly confirmed 22q11.2 microdeletion who were referred to the Toronto Western Hospital Movement Disorders Centre. We performed extensive phenotyping through review of patient records to collect clinical, laboratory, radiologic, and electrophysiologic information relevant to movement disorder characterization. Descriptive statistics were used to summarize the data.

Results: The mean ± SD age of onset of any movement disorder was 33.1 ± 12.5 years, with a median (IQR) duration of symptom of 3.5 (7) years prior to evaluation by a movement disorder specialist. The majority (71.0%) of cases had two or more movement disorders on examination. The most frequent findings were non-parkinsonian tremor (71.0%), parkinsonism (48.4%), dystonia (36.7%), and myoclonus (32.1%). In 19 unpublished cases, we found additional cases of tics and functional movement disorder (FMD), and identified novel phenotypes including stereotypies as well as electrophysiologically confirmed cortical myoclonus and slow orthostatic tremor. The presence of multiple (≥ 2) movement disorders did not significantly differ between antipsychotic-naïve individuals and those with a history of antipsychotic use (70.0% vs. 71.4%, p > 0.99).

Conclusion: The majority of individuals with 22q11.2DS evaluated for a movement disorder by experts in this field exhibit multiple movement disorders, which can occur irrespective of antipsychotic use. Although parkinsonism is common, as previously reported, clinicians should be aware that other movement disorder phenotypes can exist along with or independent of parkinsonism, including non-parkinsonian tremor, dystonia, myoclonus, tics, stereotypies, and FMD. Electrophysiologic studies may support the presence of and help in further characterizing 22q11.2DS-associated movement disorders.

References: 1. Butcher NJ, Kiehl T-R, Hazrati L-N, et al. Association Between Early-Onset Parkinson Disease and 22q11.2 Deletion Syndrome. JAMA Neurol. 2013;70(11):1359. doi:10.1001/jamaneurol.2013.3646
2. McDonald-McGinn DM, Sullivan KE. Chromosome 22q11.2 Deletion Syndrome (DiGeorge Syndrome/Velocardiofacial Syndrome). Medicine (Baltimore). 2011;90(1):1-18. doi:10.1097/MD.0b013e3182060469
3. Boot E, Butcher NJ, van Amelsvoort TA, et al. Movement disorders and other motor abnormalities in adults with 22q11.2 deletion syndrome. Am J Med Genet Part A 2015; 167: 639–45.
4. Boot E, Marras C, Bassett AS. Spectrum of movement disorders and motor abnormalities in adults with a 22q11.2 microdeletion: Comment on the literature and retrospective study of 92 adults. Eur J Hum Genet 2022; 30: 1314–7.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/expanding-the-phenotypic-spectrum-of-movement-disorders-in-22q11-2-deletion-syndrome/