GNA11‐mutated Sturge‐Weber Syndrome has distinct neurologica

Background: 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). Subunit Alpha 11 (GNA11) mutations have been reported in 5 cases. It is not clear if their phenotypic features differ. Methods: Within two European multidisciplinary centers we looked for patients with clinical characteristics of SWS and a GNA11 mutation. Clinical and radiological data was collected retrospectively and prospectively. Results: We identified three patients with SWS associated with a somatic GNA11 mutation. They 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 purple color. Two of the patients had glaucoma. All had neurological symptoms and moderate brain atrophy at a lower degree of severity than classically associated with SWS. Susceptibility-Weighted Images (SWI) and contrast-enhanced (CE) Fluid Attenuated Inversion Recovery (FLAIR) MR views demonstrated best sensitivity to reveal the pial angiomas. Conclusions: We differentiate two distinct clinical/radiological phenotypes of SWS; GNAQ- and GNA11-SWS. The classical 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; neurological picture is milder. SWI and post contrast FLAIR sequences appear to be necessary to demonstrate the leptomeningeal angiomatosis. Yet, anti-epileptic medication or future targeted therapies may be useful, like in classic SWS.