24-Year-Old Patient with Klippel-Trenaunay Syndrome Underwent Cementless Robotic Cruciate-Retaining TKA: A Case Report.

CASE: A 24-year-old man with Klippel-Trenaunay syndrome (KTS) presented with severe knee osteoarthritis unresponsive to conservative measures. Owing to end-stage, debilitating arthritic symptoms, surgery was pursued. Careful preoperative, multidisciplinary planning/treatment included magnetic resonance imaging to characterize the venous malformations throughout the right lower extremity, preoperative sclerotherapy, sirolimus, and robotic-assisted cementless total knee arthroplasty (TKA). CONCLUSION: Cementless robotic-assisted TKA with selective patellar resurfacing can be a viable option for young KTS patients with severe osteoarthritis when a meticulous multidisciplinary approach, including sclerotherapy and advanced imaging, is undertaken to analyze vascular abnormalities, minimize surgical risks, preserve bone stock, and optimize outcomes.

Klippel-Trenaunay syndrome or not? An exploration of atypical presentations.

Klippel-Trenaunay syndrome (KTS) is a rare, congenital disorder typically emerging in early infancy or childhood. The classic presentation of KTS is distinguished by a triad of clinical features: a port-wine stain, early-onset varicosities and limb overgrowth. However, a notable variant of KTS has been documented, characterised by limb shortening rather than lengthening, occasionally referred to as 'inverse KTS'. This report details two cases that display this unusual presentation-both patients had classical features of port-wine stain and varicose veins but both experienced shortening of the affected limb. Whether these cases represent a variant of KTS or a new clinical syndrome altogether is uncertain. They however offer valuable insights into the nuances and breadth of clinical manifestations associated with this syndrome.

Recurrent hematuria involving urinary system with Klippel-Trenaunay syndrome: A case report.

RATIONALE: Klippel-Trenaunay syndrome (KTS) is a rare congenital venous malformation, it had been found to be caused by mutations of the phosphatidylinositol 4, 5-diphosphate 3-kinase catalytic subunit alpha (PIK3CA) gene. Currently KTS is defined as a triad of skin wine pigmented spots, varicose veins and malformations of the lower extremities, and hypertrophy of bone and soft tissue, involving urinary system up to 6% to 30%. When the urinary system is involved, KTS is often presented as painless massive gross hematuria. PATIENT CONCERNS: This article describes a woman who was hospitalized with painless massive gross hematuria. Physical examination revealed significant hypertrophy of the right lower limb with varicose veins, port-wine stains in the skin, and right perineal hemangiomatous changes with swelling. The patient was admitted to hospital 4 times for repeated hematuria and infection. DIAGNOSES: By physical examination, CT urography, ureteroscopy and cystoscopy, the patient was diagnosed to have Klippel-Trenaunay syndrome, involving the urinary system. INTERVENTIONS: The patient hematuria improved after multiple indwelling D-J tubes and anti-inflammatory treatment. OUTCOMES: The final symptoms of hematuria improved significantly, follow-up so far has not recurred. LESSONS: This case presents the possibility of painless gross hematuria with KTS. Most of patients can be improved by conservative treatment. Cystoscopic laser therapy is the preferred treatment for poor bleeding control. Cystectomy and nephrectomy should be considered when life-threatening.

Multiple Lymphaticovenular Anastomoses for Chyluria in Klippel-Trenaunay Syndrome.

ABSTRACT: Klippel-Trenaunay syndrome (KTS) is characterized by port-wine stains, mixed vascular malformations, and soft tissue and bone hypertrophy. Klippel-Trenaunay syndrome is occasionally complicated by chyluria, for which there is no effective treatment currently. We report a case of KTS complicated by intractable chyluria and hematuria due to a lymphatic-ureteral fistula. The patient was successfully treated with multiple lymphaticovenular anastomoses (LVAs).A 66-year-old woman with an enlarged left lower extremity since childhood was diagnosed with KTS. At 60 years of age, she developed chyluria (urine albumin, 2224 µg/mL) and hematuria. Lymphoscintigraphy showed a lymphatic-ureteral fistula near the ureterovesical junction. Conservative treatment was ineffective. She also developed left lower extremity lymphedema, which gradually worsened. Leg cellulitis and purulent pericarditis developed because of hypoalbuminemia (minimum serum albumin level, 1.3 g/dL).We performed 14 LVAs in 2 surgeries to reduce lymphatic fluid flow through the lymphatic-ureteral fistula. The chyluria and hematuria resolved soon after the second operation, and the urine albumin level decreased (3 µg/mL). After 28 months, she had no chyluria or hematuria recurrence and her serum albumin level improved (3.9 g/dL). Multiple LVAs can definitively treat chyluria caused by a lymphatic-ureteral fistula in patients with KTS.

Total knee arthroplasty in patients with Klippel Trenaunay syndrome and knee osteoarthritis: A case report and a literature review.

INTRODUCTION: Klippel Trenaunay syndrome (KTS) is a rare congenital disorder characterized by wine staining, varicose veins, bone hypertrophy, and soft tissue hyperplasia. KTS usually occurs at birth, early infancy or childhood. The rarity of disease makes it difficult to calculate its incidence rate. However, few studies report the incidence rate of 2 to 5 cases per 100 thousand. Furthermore, evidence demonstrates that KTS is more prevalent among males compared to females. CASE PRESENTATION: An elderly male aged 67, was admitted to the hospital for chronic pain in his left knee. An outpatient physical examination reveals a significantly thicker left lower limb accompanied by multiple varicose veins. The right lower limb was 2 cm short on the opposite side, and the right foot was stunted with high arch deformity. The entire body was covered in a red grape globus, which faded after pressing. He was diagnosed with KTS. We performed TKA for him after blood coagulation examination. The patient recovered well after the operation. He was followed up for 1 year, The patient is in good condition and satisfied with the operation. CONCLUSION: For patients with KTS, total knee arthroplasty is an effective surgical procedure to treat arthritis. However, some risks must be considered, and appropriate surgical preparation must be undertaken.

Value of the short time inversion recovery sequence of magnetic resonance imaging in the staging of Klippel-Trenaunay syndrome complicated with lymphedema.

OBJECTIVE: Currently, the focus on limb lymphedema (LE) is on classification and staging. However, few scholars have conducted staging for Klippel-Trenaunay syndrome complicated LE (KTS-LE). This study aimed to investigate the value of the short time inversion recovery sequence of magnetic resonance imaging (MRI) in the staging of KTS-LE. METHODS: Forty-six patients who were diagnosed with KTS-LE were recruited for this retrospective study from July 2011 to November 2022. Referring to the clinical staging standard of lower extremity LE of the International Society of Lymphology in 2020, all patients were divided into three groups: stages I, II, and III. The MRI indicators of the three groups were recorded and statistically compared: LE range (unilateral bilateral, lower limbs, only thighs, only calves and ankles), abnormal parts (skin thickening, abnormal subcutaneous fat signal, abnormal muscle signal, muscle hypertrophy or contraction, abnormal bone signal, hyperostosis), and subcutaneous soft tissue signs (parallel line sign, grid sign, band sign, honeycomb sign, lymph lake sign, crescent sign, and nebula sign). RESULTS: There was a significant difference in the honeycomb sign among the three periods (P = .028). There was a significant difference between stage II and stage I disease (P < .05). There was a significant difference between stage II and stage III disease (P < .05). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the honeycomb sign in diagnosing KTS-LE of stage II were 87.5%, 63.2%, 33.3%, 96.0%, and 67.4%, respectively. In contrast, the other signs were not statistically significant among the three periods. CONCLUSIONS: The short time inversion recovery sequence of MRI is of great value in KTS-LE. The honeycomb sign is an important imaging indicator for the diagnosis of stage II disease. It is necessary to evaluate the severity of edema with MRI for KTS-LE, which is very important for therapeutic options.

The Prospective Natural History Study of Patients with Intractable Venous Malformation and Klippel-Trenaunay Syndrome to Guide Designing a Proof-of-Concept Clinical Trial for Novel Therapeutic Intervention.

Background: The natural history of venous malformation (VM) and Klippel-Trenaunay Syndrome (KTS) has not been quantitatively studied. To obtain benchmarks to guide designing clinical trials to assess safety and efficacy of novel drug candidates, the clinical course of the patients was followed for 6 months. Methods and Results: This is a multicenter prospective observational study evaluating the change rate in lesion volume from baseline with magnetic resonance images, as the primary endpoint. In addition, disease severities, performance status (PS), pain visual analog scale (VAS) score, quality of life (QoL), infections, and coagulation markers were also evaluated. Thirty-four patients (VM = 17, KTS = 17, 1-53 of age; median 15.9 years) with measurable lesion volume were analyzed. There was no statistically significant difference in the lesion volume between baseline and day 180, and the mean change rate (standard deviation) was 1.06 (0.28). There were no baseline characteristics that affected the change in lesion volume over 6 months. However, there were patients who showed more than 20% volume change and it was suggested that the lesion volume was largely impacted by local infection. There were no statistically significant changes in pain VAS score, severity, PS, QoL score, D-dimer, and platelet count over 6 months within all patients analyzed. Conclusion: The results showed the representative natural course of VM and KTS for a 6-month period with objective change of lesion volume and other factors, suggesting that it is scientifically reasonable to conduct a Phase 2 proof-of-concept study without a placebo arm, using the results of this study as the control. Clinical Trial Registration: NCT04285723, NCT04589650.

Subcutaneous Cavernous Haemangioma in a Patient with Klippel-Trenaunay Syndrome: A Case Report.

Background: Klippel-Trenaunay syndrome (KTS) is a rare congenital disease that mainly involves blood vessels and is characterized by the presence of capillary malformations (port wine stains), varicose veins, soft tissue and/or bone hypertrophy. Case Presentation: We report a 28-year-old man who was diagnosed 20 years ago with Klippel-Trenaunay syndrome. Approximately 3 years ago, he found enlarged masses on both upper extremities and a new dark red mass that was pathologically diagnosed as cavernous haemangioma appeared on the right index finger. Conclusion: KTS is a rare and potentially multisystem disease requiring multidisciplinary management for which imaging examination is an important auxiliary diagnostic method. Various complications may occur during its development, so regular follow-up is required to prevent serious accidents.

Termoablación venosa de extremidad inferior en un paciente con síndrome de Klippel-Trénaunay / Lower extremity venous thermoablation in a patient with Klippel-Trénaunay syndrome

Introducción: el síndrome de Klippel-Trénaunay (SKT) es una entidad clínica rara y esporádica. La tríada clásica define malformación capilar, hipertrofia ósea y de tejidos blandos y varicosidades atípicas. Caso clínico: se describe el caso de una paciente de 14 años de edad que consulta por mancha en vino de Oporto, dolor en miembro inferior izquierdo, edema y discrepancia en la longitud de las extremidades inferiores. Se catalogó como síndrome de Klippel-Trénaunay por la tríada clásica presentada. Discusión: la paciente se benefició de termoablación venosa asociada a flebectomías y de oclusión venosa con escleroespuma.(AU)

Introduction: Klippel-Trénaunay syndrome (SKT) is a rare and sporadic disease, characterized by the clinical triad of capillary malformations, bone and soft tissue hypertrophy and varicose veins. Case report: we report the case of a 14-year-old female patient who presented a port-wine stain, pain in the left lower limb, edema, and discrepancy in the length of this limb. It was classified as Klippel-Trénaunay syndrome due to the classical triad presented. Discussion: the patient underwent venous thermoablation associated with phlebectomies and sclerofoam venous occlusion.(AU)

Active and passive mechanical characterization of a human descending thoracic aorta with Klippel-Trenaunay syndrome.

A human aorta from a female donor affected by Klippel-Trenaunay syndrome was retrieved during a surgery for organ donation for transplant. The aorta was preserved in refrigerated Belzer UW organ preservation solution and tested within a few hours for mechanical characterization with and without vascular smooth muscle activation. KCl and Noradrenaline were used as vasoactive agents in bubbled Krebs-Henseleit buffer solution at 37 °C. A quasi-static and a dynamic mechanical characterization of the full wall and the three individual layers were carried out for strips taken in longitudinal and circumferential directions. The full wall in the descending portion of the aorta underwent mechanical tests with and without smooth muscle activation. Results were compared to data obtained from healthy aortas and show a reduced stiffness of the full wall in circumferential direction. Also, a significant reduction of the response to vasoactive agents in circumferential direction was observed, while the longitudinal response was similar to healthy cases.

Klippel-Trenaunay syndrome and pregnancy: A Case-Report.

Klippel-Trenaunay Syndrome is a benign disease with a low incidence rate. Pregnant women with KTS may be at increased risk of thrombosis and coagulopathy due to normal hemodynamic changes during pregnancy. The choice of delivery route for KTS pregnant woman needs rigorous evaluation. This study reported a case of successful delivery by oxytocin combined with balloon catheter induction for the first time, providing more options for KTS pregnant woman. At the same time, this study reported a successful case of labor induced by oxytocin combined with balloon catheter for the first time, which further explored the obstetric management of pregnant women with KTS and provided them with more delivery options.

Parkes Weber syndrome: a rare cause of foot drop.

This case report describes a patient in her late 60s, previously diagnosed with Klippel-Trenaunay syndrome who presented with difficulty walking. A year prior to her presentation she had a fall which made her notice a painless foot drop on the right. Her right leg was profoundly hypertrophied compared with the left, and a port-wine stain was present on the lateral side, extending from the hip to the mid-shin. The patient's differential diagnosis based on clinical examination and investigations is discussed leading to a final diagnosis of sciatic neuropathy secondary to an arteriovenous malformation due to Parkes Weber syndrome.

Gastrointestinal involvement in Klippel-Trénaunay syndrome: pathophysiology, evaluation, and management.

Klippel-Trénaunay syndrome is typically a complex combined capillary-lymphatic-venous malformation in lower limb. Gastrointestinal involvement is not infrequent in Klippel-Trénaunay syndrome. Rectal bleeding is the most common complication. In recent years, this condition has been increasingly reported. However, most authors simply described extreme manifestations or various combinations of clinical observations. The underlying pathophysiology of gastrointestinal involvement in Klippel-Trénaunay syndrome has been underrecognized. Pathophysiologically, some seemingly adequate managements are pitfalls in treatment. Anorectosigmoid vascular malformations in KTS have distinct and more complicated pathophysiologies than anorectal vascular malformation. Once understanding the pathophysiology, some patients can be successfully managed with a staged plan in our practice. Therefore, recognizing the pathophysiologies of gastrointestinal involvement is needed to evaluate, prevent pitfalls, and determine adequate managements for practitioners. Because of the complexity and rarity of this condition, prospective controlled study or a large cohort of patients is impossible. Based on literature review and our practice, we discuss pathophysiologies, evaluation, pitfalls, and treatment strategies for gastrointestinal involvement in Klippel-Trénaunay syndrome.

Targeted next-generation sequencing for detection of PIK3CA mutations in archival tissues from patients with Klippel-Trenaunay syndrome in an Asian population : List the full names and institutional addresses for all authors.

BACKGROUND: Klippel-Trenaunay syndrome (KTS) is a rare slow-flow combined vascular malformation with limb hypertrophy. KTS is thought to lie on the PIK3CA-related overgrowth spectrum, but reports are limited. PIK3CA encodes p110α, a catalytic subunit of phosphatidylinositol 3-kinase (PI3K) that plays an essential role in the PI3K/AKT/mammalian target of rapamycin (mTOR) signaling pathway. We aimed to demonstrate the clinical utility of targeted next-generation sequencing (NGS) in identifying PIK3CA mosaicism in archival formalin-fixed paraffin-embedded (FFPE) tissues from patients with KTS. RESULTS: Participants were 9 female and 5 male patients with KTS diagnosed as capillaro-venous malformation (CVM) or capillaro-lymphatico-venous malformation (CLVM). Median age at resection was 14 years (range, 5-57 years). Median archival period before DNA extraction from FFPE tissues was 5.4 years (range, 3-7 years). NGS-based sequencing of PIK3CA achieved an amplicon mean coverage of 119,000x. PIK3CA missense mutations were found in 12 of 14 patients (85.7%; 6/8 CVM and 6/6 CLVM), with 8 patients showing the hotspot variants E542K, E545K, H1047R, and H1047L. The non-hotspot PIK3CA variants C420R, Q546K, and Q546R were identified in 4 patients. Overall, the mean variant allele frequency for identified PIK3CA variants was 6.9% (range, 1.6-17.4%). All patients with geographic capillary malformation, histopathological lymphatic malformation or macrodactyly of the foot had PIK3CA variants. No genotype-phenotype association between hotspot and non-hotspot PIK3CA variants was found. Histologically, the vessels and adipose tissues of the lesions showed phosphorylation of the proteins in the PI3K/AKT/mTOR signaling pathway, including p-AKT, p-mTOR, and p-4EBP1. CONCLUSIONS: The PI3K/AKT/mTOR pathway in mesenchymal tissues was activated in patients with KTS. Amplicon-based targeted NGS could identify low-level mosaicism from low-input DNA extracted from FFPE tissues, potentially providing a diagnostic option for personalized medicine with inhibitors of the PI3K/AKT/mTOR signaling pathway.

Síndrome de Klippel-Trenaunay en gestante, a propósito de un caso / Klippel-Trenaunay syndrome in pregnant woman, about a case

Introducción: El síndrome de Klippel-Trenaunay es un trastorno neurocutáneo que se asocia a complicaciones trombóticas y hemorrágicas graves durante la gestación. Principales síntomas y/o hallazgos clínicos: Presentamos el caso de una primigesta afecta del síndrome de Klippel-Trenaunay a la que se realizó un seguimiento estrecho del embarazo de forma conjunta con el Servicio de Medicina Física y Rehabilitación. Ingresó a la 39+2 semanas por rotura de membranas que finalizó mediante parto vaginal eutócico, con aplicación de anestesia epidural sin complicaciones. Diagnósticos principales: Desde que el síndrome de Klippel-Trenaunay fue descrito por primera vez en 1900, se han informado menos de cien embarazos de pacientes afectas de esta patología en todo el mundo. A pesar del incremento del riesgo obstétrico y la posibilidad de exacerbación de las manifestaciones propias del síndrome durante la gestación, son posibles unos buenos resultados obstétricos con un asesoramiento adecuado y un seguimiento estrecho de la gestación. Intervenciones terapéuticas y resultados: Es fundamental realizar una valoración individualizada del riesgo-beneficio de la tromboprofilaxis dadas las potenciales complicaciones hemorrágicas y trombóticas que pueden sufrir estas pacientes. Conclusión: Es necesario un asesoramiento preconcepcional cuidadoso así como una atención intraparto y posparto sistemática para reducir la morbimortalidad en estas pacientes. (AU)

Introduction: Klippel-Trenaunay syndrome is a neurocutaneous disorder that is associated with severe thrombotic and hemorrhagic complications during pregnancy. Main symptoms and/or clinical findigns: We present the case of a primigravida affected by Klippel-Tre-naunay syndrome in whom a follow-up of the pregnancy was carried out jointly with the Physical Medicine and Rehabilitation Service. She was admitted at 39+2 weeks due to rupture of the membra-nes which ended with eutocic vaginal delivery, with the application of epidural anesthesia without complications.Main diagnoses: Since the Klippel-Trenaunay syndrome was first described in 1900, less than one hundred pregnancies of patients affected by this pathology have been reported worldwide. Despite the increased obstetric risk and the possibility of exacerbation of the syndrome’s own manifestations during pregnancy, good obstetric outcomes are possible with appropriate counseling and close moni-toring of pregnancy.Therapeutic interventions and results:It is essential to carry out and individualized assessment of the risk-benefit of thromboprophylaxis given the potential bleeding and thrombotic complications that these patients may suffer.Conclusion: Careful preconception counseling as well as systematic intrapartum and postpartum care are necessary to reduce mortality and morbidity in these patients. (AU)

A rare case of Klippel-Trenaunay syndrome presenting with chronic myeloid leukemia.

BACKGROUND: Klippel-Trenaunay syndrome (KTS) is an overgrowth syndrome associated with capillary/venous/ lymphatic malformations with limb hypertrophy and cancer risk. Various cancers, mostly Wilms tumor, have been reported in patients with KTS, but not leukemia. Chronic myeloid leukemia (CML) is also a rare disease in children, where there is no known disease or syndrome to predispose to CML. CASE: We report a case of CML incidentally diagnosed in a child with KTS when he was bleeding from surgery of the left groin for vascular malformation. CONCLUSIONS: This case reflects the variety of cancer types that may accompany KTS and provides information about CML prognosis in such patients.