Cortical myoclonus as a common and clinically actionable movement disorder phenotype of 22q11.2 deletion syndrome.

BACKGROUND

Although myoclonus is known to be linked to genetic etiologies, its characterization in conditions associated with pathogenic copy number variation (CNV) remains limited.

OBJECTIVE

This study systematically characterized myoclonus in 22q11.2 microdeletion, the most common pathogenic CNV in humans.

METHODS

We identified individuals with neurophysiologically confirmed myoclonus from a large cohort of adults with 22q11.2 deletion syndrome (22q11.2DS) assessed between January 1996 and December 2025. We estimated prevalence, and analyzed clinical and neurophysiological features.

RESULTS

Among 295 neurologically assessed patients, 16 of the 42 unrelated individuals with clinically suspected myoclonus had neurophysiological data available for characterization. All 16 met predefined criteria for highly probable cortical myoclonus (minimum observed prevalence: 5.4%; 95% CI 3.4 - 8.6%), with eight meeting criteria for definite cortical myoclonus (minimum observed prevalence: 2.7%, 95% CI 1.4 - 5.3%). In 9 of the 12 patients with available follow-up clinical data, neurophysiological evaluation has led to changes in management.

CONCLUSIONS

The findings support cortical myoclonus as a relatively common and clinically actionable movement disorder in 22q11.2DS. As for Parkinson's disease, the results provide preliminary evidence supporting the chromosome 22q11.2 microdeletion as a potential risk-conferring CNV for cortical myoclonus, adding to the genetic heterogeneity associated with this movement disorder.