The Application of Clinical Genetics (Apr 2023)
Sturge-Weber Syndrome: A Review of Pathophysiology, Genetics, Clinical Features, and Current Management Approache
Abstract
Luis Fernando Sánchez-Espino,1 Marta Ivars,1 Javier Antoñanzas,2 Eulalia Baselga1 1Pediatric Dermatology Department, Barcelona Children’s Hospital Sant Joan de Dèu, Barcelona, Cataluña, Spain; 2Dermatology Department, Clínica Universidad de Navarra, Pamplona, Navarra, SpainCorrespondence: Eulalia Baselga, Department of Dermatology, Hospital Sant Joan de Deu, Passeig de Sant Joan de Déu, 2, Esplugues de Llobregat, Barcelona, 08950, Spain, Tel +34-686-68-9669, Email [email protected]: 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.Keywords: Sturge-Weber-syndrome, port-wine stain, capillary malformation, targeted therapies, GNAQ/GNA11, sirolimus
