Sturge-Weber syndrome: an overview of history, genetics, clinical manifestations, and management

Abstract

First described in the late 1800's, Sturge-Weber syndrome is one of the more common neurocutaneous disorders. In most cases, it is caused by a somatic mosaic variant in the GNAQ gene driving aberrant overgrowth in endothelial cells which leads to capillary-venous malformations. Characteristic findings are unilateral facial port-wine stain, ipsilateral parieto-occipital leptomeningeal angioma with calcifications and atrophy, and ipsilateral glaucoma, though there is significant variability. The predilection for facial skin and brain is likely due to common embryologic progenitors. The risk of brain involvement is increased with a hemifacial, forehead, or medial facial port-wine stain. Neurologic features include epilepsy, stroke-like episodes, transient or permanent hemiparesis and visual field deficit, headaches, and cognitive and behavioral impairment. Magnetic resonance imaging reveals contrast-enhancing leptomeningeal angiomatosis, progressive atrophy, calcifications, and ipsilateral dilated choroid plexus. The treatment of glaucoma typically requires surgery and port-wine stains are treated with laser therapy. Retrospective data from small cohorts show potential benefits of presymptomatic treatment with anti-seizure medications and/or low dose aspirin. Epilepsy surgery can benefit those with a greater degree of hemiparesis and intractable seizures. Low-dose aspirin has proven effective in lowering the frequency and severity of recoverable stroke-like events. Sirolimus has been reported preliminarily to have satisfactory results regarding cognitive function in pediatric patients, but is not a mainstay of treatment to date. Quality of life is often negatively affected by port-wine stain appearance, intractable seizures, headaches, and mood disorders. Future studies are warranted assessing medication and surgery outcomes, quality of life measures, and timing of imaging and treatment initiation.

Keywords: GNAQ; Leptomeningeal angiomatosis; Mosaicism; Neurocutaneous; Nevus Flammeus; Port-wine stain; Somatic.