Objective: To highlight 22q11.2 deletion syndrome (22q11.2DS) as an underrecognized genetic cause of early-onset Parkinson disease (EOPD) and to describe the diagnostic challenges in patients with schizophrenia where parkinsonism may initially be misattributed to antipsychotic-induced parkinsonism.

Background: Chromosome 22q11.2DS is a genomic microdeletion disorder characterized by congenital anomalies, neurodevelopmental impairment, and psychiatric disease.Increasing evidence indicates that 22q11.2DS is a genetic risk factor for early-onset Parkinson disease (EOPD)[1-3],with a reported prevalence of 1.8% among affected adults and a median motor onset at 45 years.In patients with psychiatric comorbidity,parkinsonism may be overlooked because symptoms are frequently attributed to chronic antipsychotic exposure [5,6].

Method: Clinical evaluation of a woman with schizophrenia and progressive parkinsonism included levodopa challenge testing,brain MRI, and fluorescence in situ hybridization (FISH).

Results: A 46-year-old Mexican ancestry woman with congenital anomalies (cleft palate,umbilical hernia,clubfoot) and developmental delay developed schizophrenia at 18,requiring chronic antipsychotics.At 36 she developed progressive parkinsonism initially attributed to antipsychotic-induced movement disorder.A levodopa challenge at 43 showed marked improvement,supporting EOPD.

Examination showed moderate intellectual disability and dysmorphic features including short stature,facial anomalies,hypoplastic dentition,palatoplasty scar with bifid uvula,clinodactyly,and camptodactyly. Neurological exam revealed asymmetric parkinsonism with rest tremor,rigidity,and bradykinesia predominating on the left. Despite wheelchair dependence from congenital lower limb deformities,she retained the ability to crawl.

Brain MRI showed white matter hyperintensities and mineral deposition in the globus pallidus (left predominance) with age-inappropriate degeneration of the substantia nigra and red nuclei (Figure 1).Calcium,thyroid profile,and parathyroid hormone were normal.FISH confirmed a 22q11.2 microdeletion (Figure 2).

Conclusion: This case highlights 22q11.2 SD as an important genetic cause of EOPD[6].In patients with schizophrenia,parkinsonism may be misattributed to antipsychotic exposure,delaying diagnosis.Dysmorphic features or congenital anomalies should prompt evaluation for 22q11.2DS.

SWI MRI: pallidal mineralization,SN/RN signal

FISH: 22q11.2 deletion

References: 1. Boot E, Butcher NJ, Udow S, Marras C, Mok KY, Kaneko S, et al. Typical features of Parkinson disease and diagnostic challenges with microdeletion 22q11.2. Neurology. 2018 Jun;90(23):e2059–67.
2. Butcher NJ, Kiehl TR, Hazrati LN, Chow EWC, Rogaeva E, Lang AE, et al. Association between early-onset Parkinson disease and 22q11.2 deletion syndrome: identification of a novel genetic form of Parkinson disease and its clinical implications. JAMA Neurol. 2013 Nov;70(11):1359–66.
3. Mok KY, Sheerin U, Simón-Sánchez J, Salaka A, Chester L, Escott-Price V, et al. Deletions at 22q11.2 in idiopathic Parkinson’s disease: a combined analysis of genome-wide association data. Lancet Neurol. 2016 May;15(6):585–96.
4. von Scheibler ENMM, Swillen A, Repetto GM, Reyes NGD, Lang AE, Marras C, et al. Prevalence of Parkinson’s Disease in 22q11.2 Deletion Syndrome: A Multicenter Study. Mov Disord Clin Pract. 2025 Jun;12(6):817–22.
5. 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 Dec;30(12):1314–7.
6. Mohamed Ibrahim N, Lin CH. Early Onset Parkinsonism: Differential diagnosis and what not to miss. Parkinsonism Relat Disord. 2024 Dec;129:107100.

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