Dissecting the Phenotypic Spectrum and Complexity of Movement Disorders in 22q11.2 Deletion Syndrome

Abstract

Background and purpose: Movement disorders are increasingly recognized as late-occurring neurologic manifestations of 22q11.2 deletion syndrome (22q11.2DS). We aimed to dissect the spectrum of relevant movement disorders in 22q11.2DS, including clinical and electrophysiologic presentations and effective therapies.

Methods: Retrospective review of medical records, medication histories, and videotaped examinations was conducted in 31 unrelated adults (55% female) diagnosed with 22q11.2DS and a movement disorder who were seen at a major center of excellence from June 1996 to September 2023. Between-group comparisons were performed to explore the influence of medications on movement disorder presentations.

Results: The median age at movement disorder onset was 35.5 (IQR: 22.0) years. Non-parkinsonian tremor was the most common phenotype (21/31, 68%), followed by parkinsonism (13/31, 42%), dystonia (11/31, 36%), myoclonus (9/31, 29%), dyskinesia (6/31, 19%), stereotypies, and functional movement disorders (4/31, 13% each). The majority of patients (24/31, 77%) presented with two or more movement disorder phenotypes (median 3, range: 2-7). Similar trends in prevalence emerged after accounting for antipsychotic exposure and potential drug-related movement disorders. Electrophysiological assessments identified both previously described and novel motor phenotypes. Treatment data for at least one movement disorder (available for 20/31, 65%) indicated a positive response to standard phenotype-based interventions.

Conclusions: We demonstrate that movement disorders in adults with 22q11.2DS exhibit greater clinical complexity than previously reported, which could reflect innate vulnerability and pathologic mechanisms beyond medication side effects. In those with a confirmed 22q11.2 microdeletion, periodic neurologic evaluations, supported by electrophysiologic investigations, enable accurate diagnosis and implementation of personalized management strategies.

Keywords: 22q11.2 deletion syndrome; 22q11.2 microdeletion; motor phenotype; movement disorder.