Cor Vasa 2026, 68(1):111-118 | DOI: 10.33678/cor.2025.106

Klippel-Trénaunay syndrome: the etiology, clinical presentation, and treatment options

Mária Rašiováa, Martin Koščoa, Marek Hudáka, Veronika Pavlíkováa, Adriana Rašiováb, Marta Bavoľárovác
a Faculty of Medicine, Department of Angiology, East Slovak Institute of Cardiovascular Diseases, Šafárik University, Košice, Slovakia
b Department of Medical and Clinical Biochemistry, Faculty of Medicine, Pavol Jozef Šafárik University in Košice, Košice, Slovakia
c Department of Internal Medicine and Cardiology, Štefan Kukura Hospital, Michalovce, Slovakia

Objective: Klippel-Trénaunay syndrome (KTS) is a combined slow-flow vascular malformation associated with excessive growth of limbs. The aim of this review is to summarize the knowledge about the presumed etiology, the most common anomalies associated with KTS, the diagnostic approach, and the treatment strategies.

Methods: A literature search was conducted between January and May 2025 using PubMed and Google Scholar databases, focusing on terms such as Klippel-Trénaunay syndrome and PIK3CA-related overgrowth spectrum (PROS).

Conclusions: KTS manifests as a cluster of congenital malformations affecting the limb and typically affects the lower extremity unilaterally. It results from a postzygotic activating mutation in the PIK3CA gene which leads to overactivation of the PI3K-AKT-mTOR signaling pathway. The clinical presentation is variable, ranging from mild forms to severe disease with the visceral organ involvement and thrombo-hemorrhagic complications. MRI-angiography is the preferred imaging modality to assess the extent of vascular malforma- tions and tissue involvement. Management of KTS often requires a multidisciplinary approach. In 2022, the FDA approved alpelisib as a systemic treatment option for patients with severe forms of KTS.

Keywords: Alpelisib, Klippel-Trénaunay syndrome, PROS, Treatment, Venous malformation

Received: July 6, 2025; Revised: July 6, 2025; Accepted: October 13, 2025; Prepublished online: June 2, 2012; Published: March 15, 2026  Show citation

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Rašiová M, Koščo M, Hudák M, Pavlíková V, Rašiová A, Bavoľárová M. Klippel-Trénaunay syndrome: the etiology, clinical presentation, and treatment options. Cor Vasa. 2026;68(1):111-118. doi: 10.33678/cor.2025.106.
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