In a 14‑year‑old with 22q11.2 deletion syndrome and catatonia, after a normal calcium level and an electroencephalogram (EEG) 25 days ago showing right‑temporal abnormalities of no clinical relevance, what additional diagnostic tests should be performed next?

Next Diagnostic Steps in a 14-Year-Old with 22q11.2 Deletion Syndrome and Catatonia

In this patient with 22q11.2 deletion syndrome presenting with catatonia, after a normal calcium level and non-contributory EEG, the next essential tests are magnesium, parathyroid hormone (PTH), phosphate, thyroid function (TSH), and a comprehensive metabolic panel including creatinine, followed by brain MRI to evaluate for structural abnormalities and movement disorder assessment. 1

Immediate Laboratory Workup

Essential Metabolic Studies

• Magnesium level is critical because hypomagnesemia can precipitate hypocalcemia and movement disorders in 22q11.2DS, and hypocalcemia may be masked if magnesium is not corrected first 1, 2
• Parathyroid hormone (PTH) must be checked even with normal calcium, as 80% of patients with 22q11.2DS develop hypocalcemia at some point in life, and relative hypoparathyroidism can exist with "normal" calcium levels 1, 2
• Phosphate levels help differentiate hypoparathyroidism (high phosphate) from other causes and assess calcium-phosphorus product 1, 2
• Thyroid-stimulating hormone (TSH) because nearly 1 in 4 adults with 22q11.2DS require treatment for primary hypothyroidism, which can contribute to psychiatric symptoms and metabolic disturbances 1
• Creatinine and renal function to evaluate for kidney disease that could affect calcium metabolism and medication clearance 1

Additional Metabolic Markers

• 25-hydroxyvitamin D level should be measured as vitamin D deficiency is common and contributes to hypocalcemia risk 1, 2, 3
• pH-corrected ionized calcium is more accurate than total calcium for detecting subtle abnormalities, particularly during stress states 2, 3

Neuroimaging Studies

Brain MRI with Specific Sequences

• Brain MRI is essential to evaluate for malformations of cortical development (polymicrogyria, focal cortical dysplasia, periventricular nodular heterotopia, hippocampal malrotation) that are associated with seizures and epilepsy in 22q11.2DS 1
• Look specifically for white matter hyperintensity signals, which are common in 22q11.2DS though their clinical relevance remains unclear 1
• Evaluate for basal ganglia calcifications, which can occur with chronic hypocalcemia and may contribute to movement disorders 4
• Assess for stroke or vascular abnormalities that may be associated with seizures in this population 1

Specialized Neurological Assessment

Movement Disorder Evaluation

• Formal neurologic examination focusing on cardinal motor features of Parkinson's disease (early-onset PD is increased in 22q11.2DS), dystonia, parkinsonism, myoclonus, and drug-induced movement disorders 1
• Standardized rating scales for movement disorders should be employed 1
• Consider dopaminergic imaging if diagnostic uncertainty exists between drug-induced versus neurodegenerative parkinsonism, though this is more relevant if antipsychotic exposure has occurred 1

Catatonia-Specific Workup

• Bush-Francis Catatonia Rating Scale or similar standardized assessment to quantify catatonia severity and track treatment response 5
• Lorazepam or zolpidem challenge test can help confirm catatonia diagnosis and predict treatment response 6, 7

Critical Pitfalls to Avoid

Metabolic Monitoring Considerations

• Do not assume normal calcium 10 days ago excludes current hypocalcemia, as calcium levels can fluctuate rapidly in 22q11.2DS, especially during biological stress states like acute psychiatric illness 1, 2
• Hypocalcemia can trigger or worsen both seizures and movement disorders even when EEG shows only non-specific abnormalities 1, 8
• Catatonia itself represents a biological stressor that can unmask latent hypocalcemia in patients with 22q11.2DS 1, 2, 5

Diagnostic Timing Issues

• The right temporal EEG abnormalities, though deemed clinically irrelevant 25 days ago, warrant repeat EEG if seizure-like episodes occur, as epilepsy risk is 4-fold higher in 22q11.2DS 1
• Calcium should be rechecked now despite being normal 10 days ago, given the acute catatonic presentation and the known calcium lability in this syndrome 1, 2, 8

Rationale for This Approach

The 2023 Genetics in Medicine guidelines emphasize that 22q11.2DS patients have multiple interconnected risks: hypocalcemia (80% lifetime prevalence), seizures (4-fold increased risk), movement disorders, and psychiatric illness including catatonia 1. Hypocalcemia can present with seizures, movement disorders, fatigue, irritability, and behavioral changes—all potentially contributing to or mimicking catatonic symptoms 1, 2, 8. The case reports demonstrate that catatonia in 22q11.2DS can have overlapping etiologies, and metabolic derangements must be excluded before attributing symptoms purely to psychiatric causes 6, 5.

Brain MRI is critical because structural abnormalities (cortical malformations, hippocampal malrotation) are associated with both seizures and cognitive/psychiatric manifestations in this population 1. The combination of metabolic workup and neuroimaging provides the foundation for distinguishing primary psychiatric catatonia from metabolically-driven or structurally-based presentations 1, 5.