What is the management approach for a patient with Leopard syndrome experiencing neurological issues?

Management of Neurological Issues in LEOPARD Syndrome

Patients with LEOPARD syndrome presenting with neurological symptoms require immediate neurological consultation and brain MRI to evaluate for structural abnormalities, as neurologic complications—though rare—can include seizures, developmental delays, and sensory deficits that significantly impact morbidity and quality of life. 1

Initial Diagnostic Evaluation

When a patient with LEOPARD syndrome develops neurological issues, the following workup is essential:

• Neurological consultation at diagnosis to establish baseline function and guide further investigation 1
• Brain MRI with and without contrast if focal neurological findings, muscle weakness, abnormal deep tendon reflexes, or severe abnormalities in muscle tone are present 1
• EEG if seizure activity is suspected, as seizures can occur in patients with RASopathies including LEOPARD syndrome 1
• Lumbar spine MRI should be considered if bowel and bladder dysfunction or lower limb upper motor neuron signs are present to rule out tethered cord, especially when a sacral dimple is present 1

Specific Neurological Manifestations to Assess

Seizures and Epilepsy

• Provoked seizures may result from metabolic derangements including hypocalcemia, hypomagnesemia, fever/infection, or medications 1
• Any seizure requires investigation including comprehensive bloodwork (calcium, magnesium, glucose), with EEG and MRI if unprovoked 1
• Anti-epileptic drug therapy is indicated for recurrent unprovoked seizures, high-risk features for recurrence (two or more unprovoked seizures, structural brain abnormalities, focal neurological signs, or epileptiform EEG) 1

Sensory Deficits

• Sensorineural deafness is a cardinal feature of LEOPARD syndrome and should be formally assessed with audiometry 1, 2
• Visual impairment may occur and requires ophthalmologic evaluation 1
• Baseline hearing and vision screening should be performed at diagnosis 1

Developmental and Motor Issues

• Mental retardation/intellectual disability can occur in LEOPARD syndrome patients 1
• Motor delays and hypotonia are common early neurologic features requiring assessment 1
• Gait disturbances and muscle weakness should prompt detailed neuromuscular evaluation 1

Management Algorithm

For Acute Neurological Symptoms:

1. Rule out life-threatening causes: metabolic derangements (hypocalcemia, hypoglycemia), infection, stroke, or increased intracranial pressure 1
2. Obtain urgent neuroimaging (brain MRI with contrast) for focal deficits, altered mental status, or severe headache 1
3. Perform EEG for suspected seizure activity or encephalopathy 1
4. Check comprehensive metabolic panel including calcium, magnesium, glucose, and thyroid function 1

For Chronic/Progressive Symptoms:

1. Early intervention services including physical therapy, occupational therapy, and speech therapy to maximize function 1
2. Regular neurological follow-up for ongoing seizure management if present 1
3. Neuropsychological evaluation upon school entry to guide educational planning 1
4. Monitor for progression of structural abnormalities with serial imaging if initial MRI shows abnormalities 1

Critical Pitfalls to Avoid

• Do not assume all neurological symptoms are benign manifestations of LEOPARD syndrome—structural brain abnormalities including polymicrogyria, gray matter heterotopia, and Chiari malformation, though rare, can occur and require specific management 1
• Do not overlook metabolic causes of neurological symptoms, particularly hypocalcemia which can cause seizures and should be corrected promptly 1
• Do not delay brain MRI in patients with rapid increase in head growth, infantile spasms, changes in neurological examination, or regression of skills 1
• Remember that hypertrophic cardiomyopathy is common in LEOPARD syndrome and can cause embolic stroke—maintain high suspicion for cardiac sources of neurological deficits 1, 3

Multidisciplinary Coordination

Coordinate care between neurology, cardiology, genetics, and developmental specialists as cardiac complications (particularly hypertrophic cardiomyopathy) can contribute to neurological morbidity through embolic phenomena or reduced cerebral perfusion 1, 3. If infantile spasms occur and steroid management is considered, consult with cardiology due to risk of cardiomyopathy exacerbation 1.