Movement Disorders Associated with 22q11.2 Microdeletion: A Scoping Review

Movement disorders have recently emerged as important neurologic manifestations of the 22q11.2 microdeletion that affects nearly one in every 2000 live births.

We aimed to map the existing evidence regarding the spectrum, diagnosis and treatment, and etiopathogenesis of movement disorders associated with 22q11.2 microdeletion, highlight key gaps, and provide recommendations for future research.

We conducted a comprehensive search of MEDLINE, Embase, CENTRAL, and reference lists to identify relevant clinical and preclinical studies, and summarize data on clinico-pathologic features, risk factors, and pathophysiology of movement disorders associated with molecularly defined 22q11.2 microdeletions.

Forty-three (clinical: n = 41/43, 95%; preclinical: n = 2/43, 5%) studies met eligibility criteria. Most clinical studies (35/41, 85%) involved adults, of which 51% (21/41) were case series/reports, and the remainder observational studies. Key findings included: (1) emphasis on parkinsonism but emerging evidence for multiple other motor phenotypes, (2) non-specific findings on routine neuroimaging, albeit with promising early results of certain modalities (eg, volumetric analyses, molecular imaging) and fluid-based biomarkers, particularly for parkinsonism, and (3) multifaceted etiologic and pathophysiologic processes beyond those attributable to medication side effects. Prevailing gaps include research design limitations, heterogeneity of diagnostic methods, and limited systematic data on etiopathogenesis and treatments.

Current evidence supports an expanding spectrum of motor phenotypes associated with 22q11.2 microdeletion, with emerging data reporting potentially useful clinical markers and non-drug-related risk modifiers and underlying mechanisms. Addressing prevailing gaps will require enhanced research designs with up-to-date diagnostic and genetic methodologies, robust preclinical models, and cross-disciplinary collaborations.