What is the management approach for seizures and calcium disorders in patients with velocardiofacial syndrome?

Management of Seizures and Calcium Disorders in Velocardiofacial Syndrome

Seizures in velocardiofacial syndrome (22q11.2 deletion syndrome) should be managed by first correcting hypocalcemia and hypomagnesemia, followed by standard antiepileptic therapy tailored to seizure type, with careful attention to the lowered seizure threshold and increased risk of medication side effects in this population. 1

Calcium Disorder Management

Initial Assessment and Monitoring

• Measure calcium, parathyroid hormone, magnesium, thyroid-stimulating hormone, and creatinine concentrations regularly, as hypocalcemia associated with hypoparathyroidism affects most patients with velocardiofacial syndrome and can arise or recur at any age 1
• Hypocalcemia may present asymptomatically, with fatigue and irritability, or with serious manifestations including seizures, cardiac arrhythmias, QT prolongation, and rarely cardiomyopathy 1
• Implement targeted calcium monitoring during high-risk periods: peri-operatively, perinatally, during pregnancy, acute illness, surgery, fracture, or any biological stress 1

Treatment Approach

• Prescribe daily vitamin D supplementation for all adults with velocardiofacial syndrome, sometimes with calcium supplementation 1
• Reserve hormonally active vitamin D metabolites (e.g., calcitriol) for more severe or refractory cases, typically with endocrinologist consultation 1
• Exercise caution to avoid overcorrection, which can result in iatrogenic hypercalcemia, renal calculi, and renal failure—this can occur inadvertently with dehydration or treatment compliance changes 1
• Address contributory conditions including hypothyroidism and hypomagnesemia when present 1

Seizure Management

Seizure Types and Etiology

• Adults with velocardiofacial syndrome have a 4-fold increased risk of epilepsy and may experience various seizure types: generalized tonic-clonic, typical or atypical absences, myoclonic, or focal seizures with preserved or impaired awareness 1
• Acute symptomatic or provoked seizures may be secondary to hypocalcemia, hypomagnesemia, fever, or medications 1
• Some patients may have seizures associated with stroke or malformations of cortical development (polymicrogyria, focal cortical dysplasia, periventricular nodular heterotopia, hippocampal malrotation) 1

Diagnostic Evaluation

• Obtain brain MRI in cases of rapid head growth increase, infantile spasms, changes in neurologic examination, or regression of skills 1
• Perform EEG if there is suspicion of seizure activity, with accurate seizure classification using clinical history and EEG to guide medical management 1
• Conduct periodic neurologic assessments for seizures/seizure-like episodes, supplemented by standardized rating scales and ancillary procedures 1

Treatment Strategy

• Correct the underlying electrolyte disturbance (hypocalcemia, hypomagnesemia) as the primary treatment before or concurrent with antiepileptic therapy 1, 2
• Tailor treatment of seizures to seizure type and contributing conditions, following standard management for idiopathic epilepsy 1
• Use a "start low, go slow" approach to medication dosing due to the lowered seizure threshold and potential for increased medication side effects in velocardiofacial syndrome 1
• For infantile spasms, consult with a cardiologist before initiating steroid management due to risk of cardiomyopathy 1
• Seizures in velocardiofacial syndrome are often refractory to medications and may require multiple anticonvulsants, though polytherapy increases risk of medication-related side effects in patients who already have learning disability and developmental delay 1

Special Considerations

• Collaborate with a 22q11.2 deletion syndrome specialist, epileptologist, and/or movement disorders neurologist for patients with suggestive features or refractory seizures 1
• Consider prophylactic anticonvulsant medication when using clozapine for psychiatric illness, given the lowered seizure threshold 1
• Monitor for hypocalcemia-induced or worsened movement disorders, as hypocalcemia can induce abnormal involuntary movements 1
• Avoid alcohol and soda drinks (especially colas), which may worsen hypocalcemia 1

Common Pitfalls to Avoid

• Do not overlook hypocalcemia as a treatable cause of seizures, even in patients with previously normal calcium levels, as hypocalcemia can arise at any age despite apparent childhood resolution 1, 2
• Avoid endless searches for physical causes when psychiatric illness is the primary issue requiring treatment 1
• Do not use stimulants for hyperactivity without careful consideration, as standard treatments may not be effective or may be potentially harmful in velocardiofacial syndrome 3
• Monitor carefully for medication side effects given the increased sensitivity in this population 1