A Novel Splice Site Mutation in the RASA1 Gene Causing Rare Diffuse Gastrointestinal Vascular Malformations: A Case...

RASA1-related disorders typically present as capillary malformation-arteriovenous malformation (CM-AVM) syndrome; visceral, especially diffuse gastrointestinal (GI) involvement has not previously been reported. We describe the first case of extensive GI vascular malformations caused by a novel RASA1 splice-site mutation. A 29-year-old man presented with 2-year intermittent hematochezia. Contrast-enhanced CT, double-balloon enteroscopy (DBE) and superior mesenteric angiography revealed diffuse vascular malformations throughout the small bowel and stomach. Targeted next-generation sequencing identified a heterozygous de-novo splice-donor mutation (NM_002890.3:c.1049+2T>G) in intron 6 of RASA1, predicted to be pathogenic. An incidental likely-pathogenic heterozygous frameshift variant in MYBPC3 (NM_000256.3:c.989del, p.Pro330HisfsTer20) was also detected. ISSVA (International Society for the Study of Vascular Anomalies) classifies it as Capillary Malformation-Arteriovenous Malformation (CM-AVM) within Fast-flow Vascular Malformations. Multidisciplinary consultation concluded that the lesions were too extensive for curative resection; the patient was discharged for close surveillance with a plan for sirolimus trial and selective surgical, Interventional or endoscopic hemostasis as needed. This case expands the phenotypic spectrum of RASA1 loss-of-function variants to include diffuse GI vascular malformations. When young patients present with obscure GI bleeding and imaging suggests multifocal angiodysplasia, germline RASA1 analysis should be considered. Early molecular diagnosis facilitates family counseling, targeted surveillance, and personalized therapy.