Extensive venolymphatic involvement in infantile Klippel-Trenaunay syndrome: A rare case from Ethiopia

Abstract

Klippel–Trenaunay syndrome (KTS) is a rare congenital disorder characterized by a triad of clinical features: capillary malformations, venous varicosities, and hypertrophy of soft or bony tissues. This case report presents a 1-year-old infant diagnosed with KTS, exhibiting multifocal pelvic, gluteal, and thigh macrocystic lymphatic malformations alongside significant limb overgrowth. The diagnosis was confirmed through clinical evaluation and advanced imaging techniques, including Doppler ultrasound and CT angiography. KTS poses unique challenges in diagnosis and management, necessitating a multidisciplinary approach to address potential complications such as deep vein thrombosis and chronic pain. This case underscores the importance of early diagnosis and ongoing monitoring in improving patient outcomes and highlights the need for increased awareness of the multiple imaging spectra of KTS among healthcare professionals.

Introduction

Klippel–Trenaunay Syndrome (KTS) is a rare congenital disorder with an incidence of approximately 2 to 3 per 100,000 live births without sex or ethnic predilection [1]. It is characterized by a classic triad of clinical features: capillary malformations (such as hemangiomas or port-wine stains), venous varicosities, and hypertrophy of bony or soft tissues. The diagnosis of KTS is typically established when at least 2 of these 3 features are present. Recent studies suggest that KTS arises from somatic mutations in the PIK3CA gene, placing it within the PIK3CA-related overgrowth spectrum (PROS) disorders [2]. In addition to the primary triad, KTS may also present with lymphatic anomalies. The manifestations of KTS are predominantly unilateral, affecting the lower limbs; however, involvement of the upper limbs and trunk can occur. In rare cases, venous malformations may extend to visceral organs and spinal structures [3].

The severity of the disorder can vary widely from primarily cosmetic deformity to severe disability, chronic pain syndrome, and venous thromboembolic events. A patient with KTS may present with acute or chronic bleeding from genitourinary and bowel involvement [4].

Case presentation

A 1-year-old child was referred to the pediatric outpatient department (OPD) from a nearby general hospital for surgical evaluation with a clinical impression of hemihypertrophy and to rule out a venous compressive lesion. The child had a history of progressive enlargement of the left lower limb and a purplish-pigmented skin lesion over the left thigh and buttock, both noted since birth. There was no history of fever, and vital signs were within normal limits for age.

On physical examination, there was soft tissue hypertrophy of the left lower leg, extending into the thigh and buttock, accompanied by nonpitting pedal edema. Multiple patchy port-wine stains were observed on the lateral aspect of the right buttock and thigh (Fig. 1).

Fig. 1.

Clinical photograph showing hemihypertrophy of the left limb and multiple port-wine cutaneous stains.

Initial imaging included an abdominal ultrasound and Doppler study of the left lower limb, revealing multifocal cystic lesions within the presacral region and left thigh subcutaneous tissue—suggestive of macrocystic lymphatic malformations. Doppler studies demonstrated dilatation and tortuosity of the great saphenous vein and other superficial thigh veins, consistent with venous varicosities. Arterial Doppler evaluation showed normal high-resistance flow patterns, with no evidence of arteriovenous fistula.

To further characterize the vascular anomalies, computed tomography (CT) angiography of the lower limbs was performed. Bone windows revealed mild asymmetric left-sided bony enlargement and cortical thickening compared to the right side (Fig. 2A and B). Diffuse left-sided subcutaneous tissue hypertrophy and edema were also noted, along with multiple septated cystic lesions involving the left psoas muscle, presacral area, left gluteal region, and anterior proximal thigh. These lesions exhibited rim and septal enhancement, more prominent during the arterial phase—features consistent with macrocystic lymphatic malformation (Fig. 3, Fig. 4). Loculated fluid collections were also seen within the left pararenal space, pelvic cavity, and fascial planes of the thigh muscles.

Fig. 2.

(A and B) CT angiography of lower limb axial bone window demonstrating cortical thickening and bony enlargement.

Fig. 3.

CT Angiography axial image demonstrating arterial phase rim enhancement of macrocystic lymphatic malformation over the left psoas muscle.

Fig. 4.

Axial delayed venous phase images show, the upper image: macrocytic lymphatic malformation in the presacral space (thick arrow) extending into left gluteal muscles (thin arrow), Lower image: lymphatic malformation in the anterior proximal thigh subcutaneous tissue.

Venous phase imaging revealed focal dilatation of the left external iliac vein (EIV), the distal segment of the superficial femoral vein (SFV), and the intramuscular veins of the thigh (Fig. 5). An anomalous, tortuous superficial embryonic vein was visualized draining the dorsal foot arch, coursing through the posterior calf, and resembling a small saphenous vein (SSV). It ascended along the lateral thigh margin (lateral marginal vein) before crossing medially to drain into the common femoral vein (CFV) (Fig. 6). Another aberrant embryonic vein drained the posterior proximal thigh and gluteal region into the internal iliac vein—likely representing a persistent embryonic sciatic vein (Fig. 7).

Fig. 5.

Sagittal venous phase image of distal thigh showing a focally dilated distal segment of superficial femoral vein.

Fig. 6.

(A) Delayed venous axial image demonstrating persistent /embryonic lateral marginal vein residing over the lateral aspect of the distal thigh. (B) the marginal vein crossing to the lateral aspect from the anatomic location of SSV.

Fig. 7.

Axial images showing dilated persistent sciatic vein (upper image), and dilated superficial and deep veins of the thigh (lower image).

The visceral organs and vasculature—including the celiac, splenic, portal, renal, and mesenteric arteries and veins- appeared normal in size, attenuation, and enhancement. There was no evidence of venous thrombosis or arterial abnormality. Given the absence of complications, the parents were counseled about the condition, informed of potential future issues, and advised to apply compression stockings. Follow-up was recommended at 6-month intervals.

Discussion

Klippel–Trenaunay syndrome (KTS) presents a unique set of challenges in both diagnosis and management, particularly due to its complex clinical manifestations and the variability in presentation among affected individuals. The classic triad of capillary malformations, venous varicosities, and hypertrophy of soft or bony tissues serves as the cornerstone for diagnosis; however, the presence of additional lymphatic anomalies complicates the clinical picture [3,5]. In our case, the infant exhibited significant multifocal macrocystic lymphatic malformations, which are not only rare but also highlight the need for heightened awareness among healthcare providers. The identification of somatic mutations in the PIK3CA gene has provided valuable insights into the pathophysiology of KTS, linking it to the broader spectrum of PIK3CA-related overgrowth spectrum (PROS) disorders. This genetic understanding emphasizes the importance of early genetic counseling and potential future therapeutic interventions. Furthermore, the predominance of unilateral manifestations, particularly in the lower limbs, necessitates a tailored approach to management that considers the individual patient's needs and the potential for complications such as deep vein thrombosis, cellulitis, chronic pain and bleeding from visceral organs [[2], [3], [4]]. Common venous anomalies of the syndrome include superficial venous malformations and varicosities in atypical distributions, while deep venous abnormalities such as aplasia, duplications, and aneurysmal dilatations have also been documented. The persistence of embryonic veins, such as the lateral marginal vein of Servelle and the sciatic vein, along with incompetent valves, further supports the diagnosis of KTS. While conventional venography has traditionally been considered the gold standard for vascular assessment, its invasive nature has led to a shift towards noninvasive imaging modalities, including color Doppler ultrasound, CT, and MR venography. Among these, color Doppler sonography is the most frequently employed technique for diagnosing KTS [4]. As discussed by Liu et al., Contrast magnetic resonance lymphangiography (MRL) with gadobenate dimeglumine has been found to provide an accurate and sensitive technique for evaluating lymphatic system disorders, and lymphatic malformation plays a significant role in Klippel-Trenaunay syndrome; the lymphatic dysplasia or malformation associated with KTS bears similarities to congenital primary lymphedema, characterized by hyperplasia, hypoplasia, or aplasia of lymphatic vessels and/or lymph nodes. Additionally, macrocystic lymphatic malformations may be observed in affected individuals [6].

Differential diagnosis for KTS should consider Prader-Willi syndrome (PWS), Proteus syndrome, Maffucci syndrome, neurofibromatosis type I, Sturge–Weber syndrome, and Beckwith–Wiedemann syndrome. The presence of arteriovenous fistula in PWS is the only difference with KTS, in our case; PWS is excluded by the absence of arteriovenous fistula on CT angiography [7].

Management of KTS is primarily conservative, focusing on symptomatic relief and the prevention and treatment of complications, including deep vein thrombosis, cellulitis, chronic coagulopathy, and congestive heart failure. Patients typically require lifelong follow-up to monitor their condition and manage any arising issues [[8], [9], [10]]. Nonoperative medical management is the main modality in the treatment of symptomatic KTS patients. Rarely, and only in patient refractory to medical management, should operative intervention be considered. Patients presenting with symptoms of chronic venous disease should be initiated on a regimen of compression and elevation. Compression stockings should extend from above the affected area to the digits and should be fitted to the individual limb. The correct pressure may vary for the patient but typically ranges from 20 to 40 mm Hg. However, compliance to this garment can be difficult in the pediatric population with rapidly growing limbs along with other social factors. Low-dose aspirin should be considered as there is limited benefit to pain and swelling in patients with vascular malformations. If symptoms are refractory to compression alone, intermittent pneumatic compression can be a useful adjunct in lower extremity edema mobilization. If soft tissue inflammation develops, it should initially be managed with over-the-counter analgesics and elevation. Be mindful that this presentation is often initially sterile; therefore, antibiotics should be reserved until cellulitis with virulent organisms is suspected. Limb length discrepancies can be appropriately managed with heel inserts or compensatory shoes to avoid scoliosis as long as discrepancies are < 1.5 cm. Using the CEAP classification, operative vascular intervention should be considered when the severity of the disease progresses to greater than class 3 or potentially class 2 in some symptomatic cases [11].

There was another case report from Ethiopia involving a 6-year-old boy diagnosed with Klippel–Trénaunay syndrome (KTS) who presented with a history of genitourinary and gastrointestinal bleeding due to visceral vascular malformations [12]. Additionally, 2 pediatric case reports from Uganda and Nigeria have been documented. The Ugandan case involved a 21-day-old female neonate who presented with macrodactyly and ectrodactyly of the left foot, numerous port-wine stains on the left thoracoabdominal region, and the anteroposterior aspect of the left lower limb. The Nigerian case described a 4-year-old boy who presented with progressive, painless swelling of the right limb and multiple pigmented skin lesions [7,13].

In this report, we present a case of Klippel–Trenaunay syndrome diagnosed in an infant, characterized by multifocal pelvic, gluteal, and thigh subcutaneous and intramuscular macrocystic lymphatic malformations as the predominant imaging feature, in addition to the classical clinical triad of the syndrome. This case underscores the complexity of KTS imaging presentations and emphasizes the importance of a multidisciplinary approach to diagnosis, management, and care. Unlike the cases reported from Ethiopia and other African countries, our case has not demonstrated visceral vascular involvement to date, nor is there any associated congenital skeletal dysplasia affecting the digits.

Conclusion

Klippel–Trenaunay syndrome (KTS) is a rare and complex congenital disorder that presents considerable diagnostic and management challenges—particularly in low-resource settings where access to advanced imaging techniques such as CT angiography, MRI angiography, and MRI lymphangiography is limited. In such contexts, maintaining a high index of suspicion is essential.

Radiologists and clinicians must be proficient in identifying the diverse imaging features of lymphatic malformations that may accompany KTS, beyond the classical triad of capillary malformations, venous varicosities, and limb hypertrophy. Noninvasive imaging modalities such as color Doppler ultrasound play a crucial role in facilitating early and accurate diagnosis.

This case demonstrates that lymphatic malformations can be the predominant imaging manifestation of KTS. Radiologists should maintain a heightened index of suspicion when encountering unilateral, macrocystic lymphatic malformations with hemihypertrophy and should actively screen for the other components of the syndrome.

Early recognition enables timely intervention, minimizes complications, and improves outcomes. A collaborative, multidisciplinary approach is essential to ensure comprehensive care and ongoing monitoring, ultimately enhancing the quality of life for patients with KTS.

Patient consent

Written informed consent to have the case details and images published was obtained from the patient’s family and an exemption was obtained from our institution’s ethics committee.