Pulmonary Embolism as the Initial Presentation of Klippel-Trénaunay Syndrome

Congenital vascular malformations are an under-recognized cause of venous thromboembolism in young adults, and their early identification carries important management implications.

A 23-year-old man presented with intermediate-high risk pulmonary embolism (PE) and right ventricular dysfunction in the context of lifelong unilateral lower extremity varicosities. After classification by the PE response team, catheter-directed thrombolysis with EKOS ultrasound-assisted catheters achieved hemodynamic stabilization. Subsequent magnetic resonance venography identified extensive venous malformations, embryonic lateral vein persistence, and osseous involvement of the femoral medullary cavity, establishing a diagnosis of Klippel-Trénaunay syndrome (KTS) within the PIK3CA-related overgrowth spectrum. The patient was transitioned to long-term direct oral anticoagulation and referred for genetic counseling and PIK3CA mutation testing.

KTS, a PIK3CA-related overgrowth spectrum disorder caused by somatic PIK3CA gain-of-function mutations, confers elevated lifelong venous thromboembolism (VTE) risk because of dysmorphic venous architecture and abnormal perforator veins. Recognition of this syndrome in young patients with VTE is essential, as it directs structured long-term surveillance, individualized thromboprophylaxis, and eligibility for emerging PI3K-AKT-mTOR targeted therapies.

Young patients with unprovoked PE and unilateral, early onset varicosities warrant evaluation for congenital vascular malformations. Identifying KTS enables multidisciplinary management and long-term VTE risk reduction.