Sturge-Weber Syndrome: A Review of Pathophysiology, Genetics, Clinical Features, and Current Management Approache

Abstract

Sturge-Weber syndrome (SWS) is a congenital, sporadic, and rare neurocutaneous disorder, characterized by the presence of a facial port-wine birthmark (PWB), glaucoma, and neurological manifestations including leptomeningeal angiomatosis and seizures. It is caused by a postzygotic, somatic, gain-of-function variant of the GNAQ gene, and more recently, the GNA11 gene in association with distinctive clinical features. Neuroimaging can help identify and stratify patients at risk for significant complications allowing closer follow-up; although no presymptomatic treatment has been demonstrated to be effective to date, these patients could benefit from early treatment and/or supportive interventions. Choroid plexus (CP) thickness measurements in brain magnetic resonance imaging (MRI) have a high sensitivity and specificity for early and incipient changes in SWS. In contrast, the absence of pathologic findings makes it possible to rule out associated neurological involvement and leads to periodical observation, with new imaging studies only in cases of new clinical signs/symptoms. Periodic ophthalmological examination is also recommended every 3 months during the first year and yearly afterwards to monitor for glaucoma and choroidal hemangiomas. Treatment for SWS depends on the extent and areas that are affected. These include laser surgery for PWB, anticonvulsants in the case of brain involvement, with either seizures or abnormal EEG, and medical treatment or surgery for glaucoma. Sirolimus has been used in a limited number of patients and appears to be a safe and potentially effective treatment for cutaneous and extra-cutaneous features, however controlled clinical studies have not been carried out. Better knowledge of GNAQ/GNA11 molecular pathways will help to develop future targeted treatments.

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“…Sturge–Weber syndrome (SWS) is a rare, congenital, and sporadic neurovascular disease characterized by abnormal vasculature in the brain, eyes, and skin [ 57 ]. The variants of the GNAQ gene and the GNA11 gene may be associated with SWS [ 58 ]. Sirolimus, a mammalian target of the rapamycin (mTOR) inhibitor, has been reported to be a potentially effective drug for the treatment of SWS [ 59 , 60 , 61 ].…”

Neurocutaneous Diseases: Diagnosis, Management, and Treatment

“…Sturge–Weber syndrome (SWS) is a rare neurocutaneous disorder, distinctively marked by port-wine vascular macules and café-au-lait spots on the skin and eyes [ 52 , 53 , 54 ]. Unlike many genetic conditions, SWS is not hereditary but stems from a sporadic mutation in the GNAQ gene, leading to a range of abnormalities in the eyes, skin, and brain with varied clinical presentations, from asymptomatic to severe [ 55 , 56 ].…”

“…The underlying mechanism involves a postzygotic somatic mutation in GNAQ on chromosome 9q21.2, sometimes also implicating the homogenous GNA11 gene on chromosome 19p13.3 [ 55 ]. These mutations create a defect in the Gαq protein that does not allow it to properly shut off, contributing to conditions like phakomatosis pigmentovascularis through mosaic expression [ 57 , 58 , 59 ].…”

MRC1 and LYVE1 expressing macrophages in vascular beds of GNAQ p.R183Q driven capillary malformations in Sturge Weber syndrome

“…Non-syndromic, cutaneous CM are often located on the face and neck and are known as port wine stains or port wine birthmarks. In Sturge-Weber syndrome (SWS), CM are found in the leptomeninges of the brain, the choroid of the eye, and skin, in a distinctive facial pattern [ 21 ]. The CM in the brain leptomeninges can lead to debilitating neurological symptoms such as seizures, hemiparesis, and migraines [ 31 , 32 ].…”