Genetic testing in the evaluation of individuals with clinical diagnosis of atypicalSturge–Webersyndrome

Abstract

AbstractSturge–Weber Syndrome (SWS) is a rare vascular malformation disorder characterized by abnormal blood vessels in the brain, skin, and eye. SWS is most commonly caused by a somatic mosaicGNAQ‐p.Arg183Gln variant. In this series, 12 patients presented for clinical evaluation of SWS but were noted to have atypical features, and therefore germline and/or somatic genetic testing was performed. Atypical features included extensive capillary malformation on the body as well as the face, frontal bossing, macrocephaly, telangiectasia, overgrowth of extremities, absence of neurologic signs and symptoms, and family history of vascular malformations. Five patients had a somaticGNAQorGNA11pathogenic variant, one patient had a somatic mosaic likely‐pathogenic variant inPIK3CA,and another one had a somatic mosaic deletion that disruptedPTPRD. The other five patients had germline variants inRASA1,EPHB4, orKIT. Our findings suggest that patients presenting for SWS evaluation who have atypical clinical characteristics may have pathogenic germline or somatic variants in genes other thanGNAQorGNA11. Broad germline and somatic genetic testing in these patients with atypical findings may have implications for medical care, prognosis, and trial eligibility.