GNA11‐mutated Sturge–Weber syndrome has distinct neurological and dermatological features

Background and purpose Sturge–Weber syndrome (SWS) is a neurocutaneous disorder characterized by clinical manifestations involving the brain, eye and skin. SWS is commonly caused by somatic mutations in G protein subunit Alpha Q (GNAQ). Five cases of subunit Alpha 11 (GNA11) mutations have been reported. We studied phenotypic features of GNA11‐SWS and compared them with those of classic SWS. Methods Within two European multidisciplinary centers we looked for patients with clinical characteristics of SWS and a GNA11 mutation. Clinical and radiological data were collected retrospectively and prospectively. Results We identified three patients with SWS associated with a somatic GNA11 mutation. All had disseminated capillary malformation (CM) and hyper‐ or hypotrophy of an extremity. At birth, the CMs of the face, trunk and limbs were pink and patchy, and slowly darkened with age, evolving to a purple color. Two of the patients had glaucoma. All had neurological symptoms and moderate brain atrophy with a lower degree of severity than that classically associated with SWS. Susceptibility‐weighted imaging (SWI) and contrast‐enhanced fluid‐attenuated inversion recovery (FLAIR) magnetic resonance imaging demonstrated the best sensitivity to reveal the pial angiomas. Conclusions We have differentiated two distinct clinical/radiological phenotypes of SWS; GNAQ‐ and GNA11‐SWS. The classic GNAQ‐SWS is characterized by a homogeneous dark‐red CM, commonly associated with underlying soft tissue hypertrophy. The CM in GNA11‐SWS is more reticulate and darkens with time, and the neurological picture is milder. SWI and post‐contrast FLAIR sequences appear to be necessary to demonstrate leptomeningeal angiomatosis. Anti‐epileptic medication or future targeted therapies may be useful, as in classic SWS. GNA11‐Sturge–Weber syndrome (SWS) has a lower degree of severity than classic SWS. Prominent clues to the radiological diagnosis are: only faint atrophy without abnormal signal intensity changes of diseased brain areas (asterisks), prominent involvement of cortical veins (arrows, left panel) instead of radial veins (seen in GNAQ‐SWS) on susceptibility‐weighted imaging, and best depiction of pial angioma on contrast‐enhanced fluid‐attenuated inversion recovery views (arrows, right panel).