Sturge-Weber Syndrome

Sturge-Weber syndrome (SWS; encephalotrigeminal angiomatosis) is a sporadic neurocutaneous disorder with an incidence of about 1 in 20,000 to 50,000, caused by a postzygotic somatic activating mosaic variant in GNAQ (R183Q; in about 90% of cases) or related genes (GNA11), which activates downstream signalling (MAPK and mTOR).

It is characterised by capillary malformation of the face (port wine birthmark), ipsilateral leptomeningeal angiomatosis and glaucoma. Chronic venous hypertension, impaired cerebral venous drainage and venous stasis lead to hypoxia, calcification and progressive brain injury.

Roux classification: type I (facial and leptomeningeal angiomas, with or without glaucoma), type II (facial angioma alone, with or without glaucoma, no intracranial disease), type III (isolated leptomeningeal angioma). Risk of SWS in an infant with a port wine birthmark involving the forehead or upper eyelid (V1 distribution) is about 8 to 25%; with V1, V2 and V3 involvement it is higher.

• Port wine stain, flat red purple lesion in the ophthalmic (V1) trigeminal region, may be bilateral
• Seizures (75 to 90%) starting in the first year of life, usually focal motor seizures that can progress to clusters and status epilepticus, and that are often stroke like episodes with transient hemiparesis, migraine, and neurological decline
• Neurological: developmental delay and intellectual disability (about 50 to 60%), hemiparesis, hemianopia, headaches, and stroke like episodes
• Eye: glaucoma (about 30 to 70%; bimodal onset: infantile with buphthalmos and late childhood or adolescence), choroidal haemangioma ("tomato catsup" fundus), and heterochromia
• Endocrine: growth hormone deficiency, central hypothyroidism
• Soft tissue and bone overgrowth under the capillary malformation (gingival hypertrophy, macrocheilia, and maxillary overgrowth)

• Diagnosis is clinical and by MRI with gadolinium (leptomeningeal enhancement; enlarged choroid plexus, abnormal deep venous drainage, atrophy, and white matter changes); susceptibility weighted imaging shows medullary and deep veins. Cranial calcification ("tram track" gyriform calcification) on CT or radiographs appears after 2 years. EEG shows reduced amplitude and epileptiform discharges. Neonatal MRI may be negative, and repeat imaging at 6 to 12 months is advised if risk remains. Ophthalmological screening: intraocular pressure measurement, gonioscopy, and fundus examination at diagnosis, every 3 months in infancy, and then every 6 to 12 months for life. Genetic testing for GNAQ in affected tissue (not in blood).

• Seizures: early and aggressive treatment since seizures drive neurological injury; oxcarbazepine or levetiracetam as first line; low dose aspirin 3 to 5 mg/kg/day (reduces stroke like episodes and seizure frequency in some patients; benefit uncertain); multi drug therapy with clobazam, valproate or topiramate; rescue benzodiazepines (buccal midazolam 0.3 mg/kg); ketogenic diet; epilepsy surgery (hemispherectomy or lobectomy) for drug resistant unilateral disease, with excellent seizure freedom and best done early (before 2 years if possible).
• Stroke like episodes: hydration, antiepileptics, and prevention of triggers (dehydration, head injury).
• Migraine: standard abortive and prophylactic therapy.
• Glaucoma: topical beta blockers (timolol 0.25 to 0.5%), carbonic anhydrase inhibitors (dorzolamide), prostaglandin analogues; surgery (goniotomy, trabeculotomy, trabeculectomy, shunt) for infantile glaucoma.
• Port wine stain: pulsed dye laser treatment beginning in infancy (every 4 to 8 weeks for multiple sessions); topical sirolimus; avoid sun damage.
• Endocrine: thyroid function and growth screening; GH if deficient.
• Neurodevelopmental support: physical, occupational and speech therapy, and educational support.
• Targeted therapy: sirolimus is under study in SWS.
• Genetic counselling: sporadic condition, so recurrence risk in family is negligible.