Surgical management of a thoraco-lumbar extradural cyst in a pediatric patient with Klippel-Trenaunay syndrome: a case report.

Introduction and importance: Klippel-Trenaunay syndrome (KTS) is a congenital disorder characterized by the abnormal development of blood vessels, soft tissues, bones, and the lymphatic system. The syndrome is rare, with few cases reported worldwide, especially those describing an association between KTS and spinal extradural meningeal cysts (SEMC). This report highlights a rare case of a pediatric patient with KTS who underwent successful surgical decompression of a thoraco-lumbar extradural cyst, highlighting the importance of reevaluating surgical interventions in KTS patients. Case presentation: A 15-year-old girl diagnosed with KTS 4 days postnatally, was referred to our clinic due to chronic back pain and spastic paraparesis. These symptoms were attributed to a compressive extradural thoraco-lumbar cyst. Diagnostic evaluations confirmed the presence of the cyst, leading to the decision to proceed with surgical intervention. Clinical discussion: The surgical approach involved a laminoplasty at T11-T12-L1, resulting in the total removal of the cystic lesion. The patient exhibited a complete resolution of symptoms postoperatively, with no significant complications reported during the surgery. Conclusion: With this case, the authors question the fear of surgical intervention in KTS patients, which is often avoided due to concerns of high-risk complications like excessive bleeding or poor wound healing, and hint at a possible association between KTS and extradural meningeal cysts.

Dermato-Radiological Evaluation of Congenital Limb Overgrowth Vascular Syndromes.

International Society for the Study of Vascular Anomalies classification defines Congenital Limb Overgrowth Vascular Syndromes (CLOS) as a subset of vascular syndromes with other abnormalities that present with unilateral limb overgrowth. It includes Klippel-Trenaunay Syndrome, Parkes-Weber Syndrome, CLOVES (Congenital Lipomatous Overgrowth, Vascular Malformations, Epidermal Nevi, Spinal/Skeletal Anomalies/Scoliosis) Syndrome, Proteus Syndrome, PTEN Hamartomatous Syndrome, and Fibroadipose Vascular Anomaly. Due to their rare and complex nature, a multidisciplinary approach to diagnosis and treatment is required. A thorough clinical and radiological workup can go miles in reflecting on the patient's outcome. Here we report five cases of CLOS with their detailed dermato-radiological profiles.

Moving Beyond Hemangioma: Interactive, Multidisciplinary, Case-Based Teaching in Vascular Anomalies for Pediatric Residents.

Introduction: Vascular anomalies are a spectrum of disorders, including vascular tumors and malformations, that often require multispecialty care. The rarity and variety of these lesions make diagnosis, treatment, and management challenging. Despite the recognition of the medical complexity and morbidity associated with vascular anomalies, there is a general lack of education on the subject for pediatric primary care and subspecialty providers. A needs assessment and the lack of an available standardized teaching tool presented an opportunity to create an educational workshop for pediatric trainees using the POGIL (process-oriented guided inquiry learning) framework. Methods: We developed a 2-hour workshop consisting of an introductory didactic followed by small- and large-group collaboration and case-based discussion. The resource included customizable content for learning assessment and evaluation. Residents completed pre- and posttest assessments of content and provided written evaluations of the teaching session. Results: Thirty-four learners in pediatrics participated in the workshop. Session evaluations were positive, with Likert responses of 4.6-4.8 out of 5 on all items. Pre- and posttest comparisons of four content questions showed no overall statistically significant changes in correct response rates. Learners indicated plans to use the clinical content in their practice and particularly appreciated the interactive teaching forum and the comprehensive overview of vascular anomalies. Discussion: Vascular anomalies are complex, potentially morbid, and often lifelong conditions; multispecialty collaboration is key to providing comprehensive care for affected patients. This customizable resource offers a framework for trainees in pediatrics to appropriately recognize, evaluate, and refer patients with vascular anomalies.

Rare Presentation of the Vein of Servelle in a Case of Klippel-Trenaunay Syndrome.

Klippel-Trenaunay syndrome (KTS) is a rare congenital vascular syndrome involving bone and soft tissue hypertrophy of the involved limb and vascular malformations of the lymphatic, capillary, and venous systems. It is often confused with Parkes-Weber syndrome (PWS). KTS is characterized by a triad of capillary malformation in the form of port wine stains, bone or limb hypertrophy, and varicose veins. The vein of Servelle, also known as the lateral marginal vein, is one of the two persisting embryonic veins of the leg, the persistent sciatic vein being the other. Truncal vascular malformation can be a complication of failure of obliteration of these veins. We present a case of a 24-year-old male of KTS who had varicose veins in his right lower limbs since five years of age and macrodactyly with a synchronous presentation of the vein of Servelle.

A Case of Klippel-Trenaunay Syndrome Complicated by Group A Streptococcemia and Multiple Organ Failure.

Klippel-Trenaunay syndrome (KTS) is a rare congenital disorder defined as a triad of capillary malformation, venous malformation, and hypertrophy of soft tissue and bones, with or without lymphatic malformation. We report a case of a KTS patient with a hospital course complicated by Group A Streptococcus bacteremia and multiple organ failure. The 39-year-old female with KTS presented to the emergency department with a fever, tachycardia, hypotension, and profuse diarrhea for one week. Blood cultures grew Group A Streptococcus necessitating a multi-antibiotic regimen and intravenous immunoglobulins (IVIG). Secondary to septic shock, the patient's renal function continuously declined requiring eight rounds of hemodialysis. She was electively intubated due to worsening acute hypoxic respiratory failure. Chest X-rays demonstrated consolidation, pneumonitis, pleural embolism, and effusions. The patient also required eight units of packed RBC throughout her hospitalization. An underlying autoimmune etiology was suspected due to multiorgan involvement and abnormal blood smears, which was confirmed by an autoimmune panel. The patient ultimately was stabilized and was optimized for discharge. This case demonstrates the importance of a multidisciplinary approach in managing patients with KTS due to their associated lymphatic abnormalities that predispose them to severe infections.

Elastic Banding Compression as a Novel Treatment to Maintain Hemodynamics in a Patient With Klippel-Trenaunay Syndrome.

Klippel-Trenaunay syndrome (KTS) is also associated with venous thrombosis originating from varicose veins in the lower extremities, pulmonary embolism, and pulmonary hypertension. This study describes the anesthetic management of laparoscopic cholecystectomy in a 54-year-old male KTS patient with orthostatic hypotension due to massive varicose veins in the lower extremities and pulmonary thromboembolism. Compressing the varicosities with an elastic bandage can maintain stable circulatory dynamics even under general anesthesia management to prevent position and insufflation-induced changes that can occur spontaneously.

Klippel-Trénaunay syndrome with profound abdominal lymphatic-venous malformation in a three-day-old newborn: a case report and literature review.

Background: Klippel-Trénaunay syndrome, a kind of congenital limb-length-discrepancy disorder, is commonly associated with a variety of vascular anomalies. Case presentation: We present the case of a three-day-old newborn with a profound abdominal mass lesion during prenatal magnetic resonance imaging (MRI) examination. After delivery, physical examination revealed mild hemihypertrophy of the left lower extremity and red lesions on the left thigh. MRI of the abdomen showed a cyst-like lesion measuring 6.3 cm × 2.7 cm × 5.5 cm in the upper abdomen. Within the mass, there were also some possible calcified spots exhibiting high T1WI signals and low T2WI signals. A computed tomography (CT) scan of the abdomen was consistent with an ill-defined cystic tumor with small calcifications and encasement of mesenteric vessels. A MRI of the left lower extremity showed a tubular structure with a signal void and homogeneous strong enhancement located in the anterior subcutis of the left lower limb. The CT scan confirmed that the tubular structure was consistent with a venous malformation. This patient had features of Klippel-Trénaunay syndrome, including port-wine stains, a profound abdominal mass, and vascular malformations of the left lower extremity. Conclusions: In this article, we presented a case of Klippel-Trénaunay syndrome, emphasizing both prenatal and confirmatory postnatal cross-sectional imaging findings. The rare presentation of an abdominal lymphatic-venous formation played a pivotal role as a crucial indicator for an early diagnosis of Klippel-Trénaunay syndrome.

Rare scrotal chylous effusion: A case report.

Klippel-Trenaunay syndrome is a rare congenital malformation predominantly affecting lower limb. In most cases, it is characterized by a classic triad of cutaneous capillary malformation (port-wine stain), lymphatic and venous abnormalities, in association with variable soft tissue and bone overgrowths. We describe a 48-year-old male presenting on the genitalia several whitish vesicles discharging a milky fluid compatible with chyle. Extensive radiology workup revealed pelvic megalymphatic malformations. Pelvic lymphatic ligations and bleomycin sclerotherapy only allowed a partial improvement. Given the high potential of recurrence, the patient will soon undergo a genetic evaluation for PIK3CA gene mutation and may need further systemic treatment with Sirolimus. As this scrotal chylous effusion in the setting of Klippel-Trenaunay syndrome is rare and highly affects the quality of life, we wanted to raise awareness of this entity and its management.

A multidisciplinary approach to managing lymphorroea in primary lymphoedema: a case study.

This case study describes the successful management of a patient with primary lymphoedema, who was experiencing lymphorrhoea and epidermolysis, using a multidisciplinary approach. The patient had Klippel-Trenaunay syndrome. The multidisciplinary team, in an outpatient clinic in Japan, included a certified lymphoedema therapist, plastic surgeons, and a wound, ostomy and continence nurse. The team performed complex physical therapy and lymphaticovenular anastomosis, which promoted the resolution of the lymphorrhoea. This resulted in improvements in skin condition, the prevention of recurrent cellulitis, and no increase in limb circumferences during the 1-year follow-up period. This report highlights the importance of a multidisciplinary approach to lymphoedema management, including lymphorrhoea control that fitted in with the patient's daily life. It is hoped that this article will contribute to the improvement of the quality of life of patients with lymphoedema.

Klippel-Trenaunay Syndrome: To Be or Not to Be Afraid.

Klippel-Trenaunay syndrome (KTS) is a rare genetic syndrome comprising an abnormal development of soft tissues and the lymphovascular system with bony overgrowth, venous malformation, and port wine stains. We present an interesting case of a three-year-old child brought to our hospital with a swollen limb and raised skin lesions associated with bleeding from minor trauma. Most of the clinical characteristics of KTS were seen in our patient, including arteriovenous, soft tissue, capillary, and lymphatic abnormalities. The diagnosis of KTS is based on clinical examinations and imaging investigations. He had gross hypertrophy of the left lower limb with measurable lengthening compared to the opposite limb. Ultrasonography of the left limb revealed soft tissue hypertrophy with abnormal venous communication. The management of KTS is mainly symptomatic and should be approached conservatively if the patient has functional limbs without edema, bleeding, ulceration, or pain.

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.

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.

Síndrome Klippel-Trenaunay en el embarazo. Reporte de un caso y revisión de la literatura / Klippel-Trenaunay syndrome in pregnancy. Case report and literature review

Resumen Antecedes: El síndrome de Klippel-Trenaunay (KTS) es un síndrome de malformación vascular que comprende una afectación variable de capilares cutáneos, venas y linfáticos con hipertrofia de tejidos blandos y huesos de la extremidad afectada. Durante el embarazo estas malformaciones se incrementan, con afectación pélvica e intraabdominal. Caso clínico: Paciente de 15 años, primigesta, con síndrome Klippel-Trenaunay diagnosticado al nacimiento, con embarazo a término, referida por iniciar con trabajo de parto para finalización del embarazo en un hospital de tercer nivel. No cuenta con control obstétrico, estudios prenatales ni ultrasonidos obstétricos. Se realiza una ecografía pélvica en donde se descartóla presencia de varices pélvicas y un doppler que evidenció un sistema venoso conservado. Se realiza terminación del embarazo vía abdominal obteniendo un recién nacido vivo masculino, peso de 3045 gramos, APGAR 9 y 9 al minuto y a los 5 minutos. Resultados: El embarazo en pacientes con síndrome de Klippel-Trenaunay tiene alto riesgo de tromboembolismo y complicaciones hemorrágicas. La valoración debe ser por un equipo multidisciplinario capacitado para anticiparse a las potenciales complicaciones. Limitaciones del estudio o implicaciones: La principal limitación es la baja incidencia de esta patología. Se puede concluir que el diagnostico de SKT no es indicación de interrupción del embarazo. El éxito del manejo de estas pacientes requiere la participación de un equipo multidisciplinario. Originalidad o valor: Este caso clínico es de primordial relevancia ya que en la bibliografía internacional están reportados menos de 100 casos de embarazos complicados con este síndrome.

Abstract: Background: Klippel-Trenaunay syndrome (KTS) Klippel- Trenaunay syndrome (KTS) is a vascular malformation síndrome that includes variable involvement of skin capillaries, veins and lymphatics with hypertrophy of soft tissues and bones of the affected limb. During pregnancy, these malformations increase, with pelvic and intra-abdominal involvement. Clinical case: 15-year-old patient, gravida 0, with Klippel- Trenaunay syndrome diagnosed at birth, with full-term pregnancy, referred for initiating labor for resolution of pregnancy in a third level hospital. Without obstetric control, without prenatal studies or obstetric ultrasounds. A pelvic ultrasound was performed, which ruled out the presence of pelvic varices and a Doppler that showed a preserved venous system. The pregnancy was terminated by abdominal route, obtaining a male newborn, weighting 3045 grams, APGAR 9 and 9 after 1 and 5 minutes. Results: Pregnancy in patients with Klippel-Trenaunay síndrome has a high risk of thromboembolism and bleeding complications. They should be evaluated by a trained multidisciplinary team to anticipate possible complications. Study limitations or implications: The main limitation is the low incidence of this pathology. It can be concluded thatthe diagnosis of SKT is not an indication for termination of pregnancy. Successful management of these patients requires the participation of a multidisciplinary team. Originality or value: This clinical case is of primary relevance since fewer than 100 cases of complicated pregnancies with this syndrome are reported in the international literature.

Klippel-Trénaunay Syndrome and Developmental Coxa Vara in the Same Limb: A Case Report with a Review of the Literature.

We present a case of a 14-year-old girl who was first treated when she was 4 years old. She had progressive limping of the left lower limb from the age of 3 years. She was diagnosed to have developmental coxa vara of the left hip and treated by a subtrochanteric valgus osteotomy of the left femur. Later, she developed hypertrophy of the left upper and lower limbs. There were port-wine stains over the left lower limbs with multiple superficial varicosities. Her diagnosis was Klippel-Trénaunay syndrome (KTS). She is asymptomatic at the final follow-up. Both developmental coxa vara and KTS are rare conditions. We present this case to demonstrate the rarest combination of two rare conditions occurring in the same limb.

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.

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.

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.