Klippel-Trenaunay syndrome with intraosseous anomalous drainage: the first case of femoral perforator vein anomaly

Introduction

Klippel-Trenaunay syndrome (KTS) represents a rare congenital vascular disorder characterized by the diagnostic triad of cutaneous port-wine stains, venous malformations, and asymmetric limb hypertrophy (1). Although cutaneous and soft tissue manifestations of KTS have been extensively documented, the pathogenesis underlying concurrent osseous cortical erosions remains poorly elucidated, with transosseous venous perforation constituting a previously unreported phenomenon in this syndrome. Herein, we present the case of a 40-year-old female exhibiting the classic triad, in whom imaging studies first documented symptomatic transcortical venous channels traversing the posterolateral femoral cortex. This case delineates a novel KTS-associated complication phenotype characterized by osseous erosion secondary to aberrant transosseous venous penetration, thereby establishing ultrasonography as a critical modality for detecting such rare osteovascular abnormalities.

Case presentation

A 40-year-old female presented to our outpatient department with a 25-year history of progressive left lower limb edema accompanied by recurrent inflammatory episodes characterized by erythema, localized hyperthermia, and tenderness. Physical examination revealed cutaneous manifestations, including port-wine stains and prominent varicosities along the lateral thigh (Figure 1A,1B). Magnetic resonance imaging (MRI) of the affected limb demonstrated subcutaneous soft tissue edema with extensive superficial venous dilatation. Radionuclide lymphoscintigraphy showed left lower limb hypertrophy with diminished lymphatic tracer uptake, non-visualization of inguinal, iliac, and lumbar lymph nodes, and diffuse subcutaneous tracer accumulation at the left ankle. Doppler ultrasonography identified: (I) marked dilation and prolonged reflux time in the lateral marginal vein; (II) a persistent sciatic vein with bidirectional flow in the posterior thigh; and (III) a highly characteristic venous channel eroding through the posterolateral femoral cortex, anastomosing with superficial venous networks (Figure 1C,1D).

Figure 1 The affected limb and ultrasound images. (A) Swelling of the left lower limb was observed, accompanied by port-wine stain lesions on the skin. The arrow indicates the site of penetration. (B) The lateral aspect of the left thigh exhibited varicose veins. The arrow indicates the site of penetration. (C) Longitudinal view: a perforating vein in the femur was observed to communicate with a network of subcutaneous superficial veins. (D) Axial view: a circumscribed defect was noted in the posterolateral cortex of the proximal left femur, with a large vein penetrating the cortical bone at the site of the defect.

The collective clinical and imaging findings fulfilled diagnostic criteria for KTS. Of particular significance was the documented transcortical venous penetration—a previously unrecognized manifestation in KTS. Conservative management comprising graduated compression therapy, short-stretch bandaging, limb elevation, and intermittent pneumatic compression was initiated. The patient has remained clinically stable at follow-up (Figure 2).

Figure 2 Timeline of symptom onset, imaging, and treatment. MRI, magnetic resonance imaging.

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s), and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was provided by the patient for publication of this article and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Discussion

KTS, officially classified under the PIK3CA-related overgrowth spectrum (PROS) by the International Society for the Study of Vascular Anomalies (ISSVA) (1), manifests as a complex low-flow combined vascular malformation characterized by the highly characteristic triad: capillary malformations (cutaneous port-wine stains), dysplastic lateral marginal vein anomalies, and asymmetric limb hypertrophy. KTS should be differentially diagnosed primarily from Parkes Weber syndrome (PWS). The key ultrasonographic feature for differentiation lies in identifying evidence of arteriovenous fistulae. The detection of high-velocity, arterial-like flow and arterialized venous spectra within the abnormal vascular territory strongly suggests PWS (2). Our case expands the phenotypic spectrum by documenting symptomatic transosseous venous penetration—a previously unreported manifestation in KTS.

Bone perforators are abnormally widened perforating veins that connect the deep veins, intrabony venous network, and superficial veins (3). Abnormal perforating veins can lead to venous insufficiency, which is radiologically characterized by prolonged reflux time and varicose veins. Doppler ultrasound is capable of demonstrating both varicose veins and valvular incompetence. For morphologically complex or atypical presentations, further evaluation with MRI, computed tomography (CT), or angiography may be employed (4). Currently, fewer than 50 cases of intraosseous venous drainage anomalies have been reported worldwide, with the vast majority localized to the tibia. To our knowledge, this represents the first reported case of KTS associated with femoral perforator vein involvement.

The identified transosseous venous anomaly eroding through the femoral cortex raises critical embryological considerations. During the 6^th–8^th gestational weeks, lower limb venous development proceeds through three distinct phases: capillary plexus formation, primordial channel specification, and final maturation with valve morphogenesis. Disruption of this process, potentially mediated by somatic PIK3CA mutations affecting PI3K-AKT-mTOR signaling pathways (5), may explain the persistent embryonic venous channels connecting intramedullary sinusoids to ectatic superficial veins.

Three mechanistic hypotheses warrant discussion (6):

• Hemodynamic theory: chronic deep venous insufficiency elevates intraosseous venous pressure, predisposing to cortical resorption and iatrogenic transcortical drainage.
• Developmental theory: aberrant venous plexus remodeling may permit retention of fetal transcortical anastomoses that are typically obliterated by 12 weeks of gestation.
• Molecular theory: PIK3CA mosaicism in mesenchymal stem cells could drive localized venous endothelial hyperplasia and osteoclastic activation via vascular endothelial growth factor (VEGF)-mediated crosstalk (5).

Treatment options for varicose veins originating from abnormal intraosseous drainage include phlebectomy, ligation, stripping, and percutaneous ablation. Sclerotherapy is not recommended due to the connection with intraosseous vascular structures. In asymptomatic cases, conservative management and regular follow-up are preferred (7). Our institutional protocol prioritizes: (I) stepwise compression therapy; (II) serial D-dimer monitoring (target <500 µg/L); and (III) biannual orthopedic surveillance for pathologic fracture risk.

In conclusion, for most patients with varicose veins that surgeons encounter, reflux is limited in the truncal and perforating veins. However, in recognition of the possibility of rare cases such as the one presented herein, ultrasonography plays a critical role in diagnosing this condition, aiding clinicians in identifying this rare entity. However, in cases with complex anatomy or deeply situated lesions, magnetic resonance venography/CT venography (MRV/CTV) can further enhance diagnostic confidence and the accuracy of preoperative planning (7). Preoperative evaluation and careful management are essential for affected patients. A limitation of this case report is the limited duration of follow-up, which currently precludes definitive assessment of therapeutic efficacy. Ongoing monitoring will be implemented to evaluate the patient’s long-term prognosis. Furthermore, the anomalous intraosseous perforator vein identified in the KTS patient presented in this study represents an extremely rare finding. The unique and uncommon nature of this case precludes its direct generalization to the broader KTS population. Its value lies in raising awareness among clinicians regarding such rare anatomical variations. We recommend that future prospective studies incorporate systematic imaging evaluation in KTS patients with skeletal involvement to better determine the true prevalence and clinical significance of such intraosseous drainage pathways.

Acknowledgments

None.

Footnote

Funding: This work was supported by Capital’s Funds for Health Improvement and Research (No. 2024-2-2085).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-2025-1327/coif). All authors report that this work was supported by Capital’s Funds for Health Improvement and Research (No. 2024-2-2085). The authors have no other conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s), and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was provided by the patient for publication of this article and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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