Arteriolymphatic Malformation in KRAS-related Parkes Weber Syndrome of Lower Limbs

The pathophysiology of arteriolymphatic malformations (ALM) in somatic KRAS-related Parkes Weber syndrome (PWS) of the lower limbs has not been reported. This study aims to characterize the clinical, imaging, and genetic features of ALM in somatic KRAS-related PWS and to redefine this entity.

This retrospective observational study (2019-2024) analyzed patients from the Vascular Anomalies Center database who met the following criteria: (1) lower limb PWS confirmed clinically/radiologically; (2) lymphatic involvement; and (3) somatic KRAS mutation in lesional tissue. The exclusion criteria were incomplete records/no genetic testing. Diagnosis of ALM requires simultaneous arterial-phase opacification of the veins and lymphatics on computed tomography angiography and/or blood-tinged chyle on direct puncture, as confirmed by correlating femoral arteriography/lymphography. The data included demographics, imaging, and somatic genetic analyses.

Twenty-seven patients (median 6 years) were included in the study. All 27 patients (100%) exhibited a discrepancy in the lower limb length (>1 cm). Somatic KRAS mutations: p.G12D (24/27, 89%), p.Q22K (3/27, 11%). ALM was radiologically confirmed. Chyle leakage occurred in 19/27 (70%) of patients. Lymphangiectasia was detected preoperatively in 18/27 (67%). Central conducting lymphatic incompetence was subclinical in 5/27 (19%). The associated anomalies included renal hypoplasia (1/27, 4%), horseshoe kidney (1/27, 4%), renal artery stenosis (1/27, 4%), femoral vein hypoplasia (2/27, 7%), and persistent sciatic vein (2/27, 7%).

This cohort delineated a distinct subtype of somatic KRAS-related PWS characterized by peripheral ALM, limb overgrowth, specific KRAS variants, and the absence of systemic involvement or germline transmission, supporting the redefinition of capillary-lymphatic-arteriovenous malformation terminology.