Morgan Delarue I am 31 years old and, since birth, I have had an overgrowth of my left lower limb, which progressively became associated with lymphangiectasia and varicosities (Figure 1a). I was diagnosed with CLOVES syndrome, which belongs to the PIK3CA-related overgrowth spectrum (PROS).1 Before identification of the PIK3CA genetic variant, I was successively diagnosed with Proteus syndrome in infancy and later with Klippel–Trenaunay syndrome. My ‘disease’ changed as the terminology evolved. These changing names were a bit confusing; however, it reveals improvement in disease understanding. PROS is a chronic and burdensome condition, responsible for significant aesthetic impairment and recurrent pain of varying intensity. During severe flares, the pain can even prevent me from carrying out certain daily activities. Despite this, I am passionate about photography, motorcycles and Formula 1 high-speed cars—interests that tend to worry my physicians. I underwent multiple therapies and multidisciplinary consultations, including surgery, sclerotherapy, topical sirolimus2 and treatment with alpelisib3 within research protocols. These therapies helped control disease progression. Throughout my medical history, beginning in childhood, I have always been very sensitive to the words used by caregivers. Positive words strengthened me, whereas negative ones had a profound and sometimes dramatic impact. I can testify that the way caregivers speak to patients truly matters, as their words can directly influence a patient's emotional state and experience of illness. Positive encounters were those in which caregivers listened to me—to my feelings and to the difficulties I was facing. In chronic diseases, patients know their condition well and are often able to recognize unusual or alarming signs. It is therefore essential that caregivers take the time to listen and trust patients when they feel that something is changing in relation to their disease. Conversely, a negative remark can deeply harm a patient and undermine their capacity to cope. I personally experienced situations in which caregivers reproached me for not being sufficiently vigilant or observant and made me feel guilty about complications of my disease; even when there was no harmful intent, these remarks—sometimes reflecting a lack of attentive listening, fatigue or professional weariness—had long-lasting and devastating effects on me. Ultimately, as a patient, I deeply wish for a relationship of trust with caregivers—one that allows for shared decision-making between the patient and the physician.4 Caroline Soares I am the mother of a 14-year-old girl with PROS affecting her left lower limb1 (Figure 1b). Her condition limits her daily activities because of pain and a sensation of limb heaviness; she cannot walk or run as easily as other children. She has undergone sclerotherapy and medical treatments (sirolimus5 and, more recently, alpelisib4 within a research protocol), and wears compression garments due to varicosities. Beyond the physical limitations, the disease represents a substantial emotional and time burden for both my daughter and our family, with ongoing worry, repeated medical appointments and the constant need to adapt daily life to her condition. My own experience as a parent was emotionally difficult at the time of her birth. She presented with clinical signs that were unfamiliar to many caregivers at the time, and I often felt that she was examined out of curiosity rather than truly cared for—as if she were a rare exhibit. I do not want my daughter to be seen as a ‘rare case’. Kindness and gentleness are central to care. These children grow up faster than others: they become familiar early with hospitals, medications, they face stigmatization, and they mature quickly as a result. According to me, shared decision-making between caregivers, parents and the child, grounded in attentive and compassionate listening, is key to successful care. We are grateful to Mrs. Silvine Taillard from the Clinical Investigation Center of Tours, France, and to Prof. Sophie Leducq, Dr. Aline Joly, Dr. Anne Le Touze, Prof. Grégoire Boulouis, Prof. Denis Herbreteau, Prof. Arnaud Paré and Mrs. Émilienne Édée, from the MAGEC-Tours Reference Center, France, for their contribution to the management of patients with superficial vascular anomalies. None. All co-authors were involved as patients or investigators in research protocols evaluating topical sirolimus and alpelisib; they report no personal financial interests. Not applicable. The patients or the patient's parents/guardians in this manuscript have given written informed consent to the publication of their case details. Data sharing is not applicable to this article as no new data were created or analyzed in this study.

ABSTRACT Background Klippel-Trenaunay syndrome (KTS) is primarily managed for vascular and soft-tissue abnormalities, while treatment of associated lymphedema remains poorly described. This study outlines our protocol for advanced lower-extremity lymphedema using a combined modified Charles’ procedure and vascularized lymph node transfer (VLNT). Methods KTS patients with International Society of Lymphology (ISL) stage III lower-limb lymphedema treated between 1999 and 2018 were retrospectively reviewed. All underwent a modified Charles’ excisional procedure with Homans techniques and VLNT. Outcomes were assessed at least one year postoperatively, focusing on early complications and postoperative hospital admissions for residual disease or recurrent infections. Results Twenty-two patients (14 male, 8 female) with a mean age of 21 years (range, 4–41) were included. Average time since KTS diagnosis was 14 years (range, 3–26). VLNT donor sites included groin (18.2%), supraclavicular (31.8%), and gastroepiploic (50%). Mean hospital stay was 16 days (range, 14–39). Follow-up averaged 38 months (range, 27–45). Three minor complications occurred (one wound dehiscence, one infection, one bleeding), and flap survival was 100%. Annual hospital admissions for soft-tissue infections decreased from a preoperative mean of 3.5 to 1.2 postoperatively. Patients required an average of 3.5 additional procedures (range, 2–8) to remove residual hemangiolymphangioma. Conclusions Lymphedema in KTS presents unique challenges and differs markedly from typical primary or secondary lymphedema. Effective management requires meticulous assessment and individualized planning. In this population, functional improvement is the main objective, and extensive debulking procedures combined with physiologic reconstruction may provide meaningful clinical benefit despite limited aesthetic outcomes.

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant vascular disorder marked by mucocutaneous telangiectasias, recurrent epistaxis, and visceral arteriovenous malformations (AVMs). Neurologic risks include brain AVMs and hemorrhagic stroke. Several rare genetic and sporadic syndromes ("HHT-like" syndromes) share overlapping vascular features, complicating diagnosis. Differentiating these conditions is essential for accurate neurovascular risk assessment. A comprehensive literature review (PubMed, Scopus, Embase, Google Scholar; 1990-2025) targeted cerebrovascular manifestations of HHT and related syndromes. Key entities included Wyburn-Mason syndrome, Cobb syndrome, Klippel-Trénaunay syndrome (KTS), neurofibromatosis type 1 (NF1), PHACE(S) syndrome, capillary malformation-AVM (CM-AVM), Parkes Weber syndrome (PWS), juvenile polyposis/HHT overlap (JP-HHT), HHT type 5 (BMP9/GDF2), PTEN hamartoma tumor syndrome (PHTS), and blue rubber bleb nevus syndrome (BRBNS). Data on gene variants, lesion types, neuroimaging, stroke risk, and neurologic outcomes were synthesized. High-flow cerebrovascular malformations similar to HHT are prominent in Wyburn-Mason syndrome, CM-AVM, and PWS, conferring a substantial hemorrhagic stroke risk. NF1 and PHACE(S) primarily feature occlusive arteriopathies linked to ischemic events. KTS, BRBNS, and PHTS predominantly show low- or mixed-flow anomalies with lower CNS hemorrhagic risk but increased thrombotic complications. JP-HHT carries added gastrointestinal cancer risk via SMAD4 variants, while HHT type 5 often presents incompletely. Genetic testing and tailored neuroimaging are critical for differentiation. Although many syndromes mimic HHT, few combine mucosal telangiectasias, high-flow AVMs, and recurrent hemorrhage. Integrating clinical, imaging, and genetic data enables precise diagnosis, risk stratification, and personalized management.

Abstract Klippel–Trenaunay syndrome (KTS) is a rare congenital limb overgrowth disorder characterised by a triad of capillary malformations, venous abnormalities and soft tissue/bone hypertrophy. This case report presents an atypical manifestation of KTS in a 22-year-old male with right calf pain and hyperpigmented skin thickening, deviating from the classical port-wine stain presentation. Clinical examination and imaging confirmed the presence of venous malformations and limb asymmetry. Management included conservative interventions such as heel modifications and compression stockings, which significantly reduced symptoms. This case highlights the importance of a multidisciplinary approach in diagnosing and managing KTS, emphasising conservative measures before surgical options.

For patients with serious illness related to a rare condition, it is critical that symptoms are adequately assessed and treated in both the inpatient and outpatient settings. The involvement of a palliative care team can be beneficial in the management of physical and emotional stressors in these situations. This case report explores the role of a specialist palliative care team in the pain management of a patient hospitalized due to complications from Klippel-Trénaunay syndrome (KTS), a rare congenital vascular malformation syndrome associated with chronic pain. With the use of a comprehensive symptom assessment, the implementation of a patient-controlled analgesia demand-button, and the use of validated tools such as the ESAS (Edmonton Symptom Assessment System) and CAGE-AID (Cutdown, Annoyed, Guilty, Eye-opener, Adapted to Include Drugs) screening, the patient achieved improved pain control, functionality, and overall well-being. This case highlights the importance of integrating palliative care in the management of complex diseases such as KTS.

Sturge-Weber syndrome (SWS) and Klippel-Trenaunay syndrome (KTS) are rare vascular malformation disorders characterised by distinct clinical features but overlapping pathogenic mechanisms, involving somatic mosaic mutations and dysregulation of the mTOR pathway. SWS typically presents with facial port-wine stains, leptomeningeal angiomas and glaucoma, while KTS is characterised by limb hypertrophy, varicosities and venous malformations without central nervous system involvement. We report an unusual case of a middle childhood boy with features of both syndromes, including extensive facial and truncal port-wine stains, seizures, glaucoma, limb hypertrophy and venous anomalies. Imaging and clinical findings confirmed the coexistence of SWS and KTS phenotypes, highlighting the diagnostic complexity of overlap syndromes. Exome sequencing did not reveal any pathogenic variants. Multidisciplinary management, including seizure control, glaucoma care, vascular interventions and psychosocial support, remains crucial. Recognition of such overlap syndromes broadens understanding of their pathogenesis and opens avenues for targeted therapies such as mTOR inhibitors.

Angiomatous lesions may be origin of even asymptomatic thromboembolic events. We report an older patient with Klippel-Trenaunay-Syndrome who presented with huge angiomatous lesions of the left upper extremity, slowly progressive dyspnea due to chronic thromboembolic pulmonary hypertension (CTEPH). Since birth his left hand, arm and shoulder were covered by venous convolutes. CT-scan showed angiomatous lesions of the thoracic wall and signs of pulmonary hypertension. Accordingly, right heart enlargement with D-sign was found in echocardiography. Right heart catheterization confirmed pulmonary hypertension with a mean PAP of 43 mmHg and a PVR of 7.5 WU. Pulmonary angiogram showed peripheral obstructions confirming the diagnosis of CTEPH. Therapeutic anticoagulation was established. As pulmonary endarterectomy was not feasible, medical treatment with riociguat was initiated and the patient underwent 5 sessions of BPA addressing 10 pulmonary segments. This resulted in significant improvement of dyspnea, right heart function, parenchymal perfusion, as well as reduction of PVR to 5 WU. We present this case because in KTS patients thromboembolism and development of CTEPH has to be kept in mind. Therapeutic options are PEA surgery, interventional with BPA, and medical treatment.

Phakomatosis, or neurocutaneous syndromes, comprises a group of genetic disorders with abnormalities involving primarily the skin and central nervous system.Skin lesions usually appear early in life, while the neurological abnormalities show a delayed onset.This group of disorders includes neurofibromatosis, tuberous sclerosis, Sturge-Weber syndrome (SWS), Klippel-Trenaunay syndrome (KTS), von Hippel-Lindau syndrome, PHACE syndrome, ataxia telangiectasia, linear nevus syndrome, hypomelanosis of Ito, and incontinentia pigmenti.SWS is a rare sporadic phakomatosis that comprises a classical triad of port wine stain (PWS), facial angiomas, and leptomeningeal angiomas with or without glaucomatous changes.KTS is also included under phakomatosis, which is characterized by the coexistence of venous abnormalities, limb hypertrophy, and cutaneous and capillary malformations. [1][2][3] Overlapping features of SWS and KTS in a single patient are extremely rare, as both syndromes occur almost always sporadically.Here, we report a case of a 28-year-old male with overlapping features of both disorders and bilateral refractory childhood glaucoma.

Klippel-Trénaunay syndrome (KTS) and Parkes Weber syndrome (PWS) are rare vascular disorders that share clinical features such as limb overgrowth and capillary malformations. However, they differ in the vascular flow dynamics. KTS is a low-flow malformation, while PWS is characterized by high-flow arteriovenous shunts. A systematic review of the literature was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, focusing on case reports and series describing patients with confirmed KTS or PWS and documented cerebrovascular or spinal vascular findings. Studies were analyzed for type and location of central nervous system lesions, and genetic data were reviewed where available. Forty studies comprising 76 patients met inclusion criteria. In KTS (61 patients), cerebrovascular anomalies were mostly venous in nature, including developmental venous anomalies, venous malformations, and cavernomas, with no spinal arteriovenous malformations reported. In contrast, PWS (n = 15) was exclusively associated with high-flow spinal arteriovenous malformations or fistulas, primarily affecting the thoracolumbar region. No cerebral lesions were identified in PWS. PIK3CA mutations were observed in KTS cases, while Ras GTPase-activating protein 1 mutations were more common in PWS. Cerebrovascular findings might offer valuable diagnostic insight into distinguishing KTS from PWS. These vascular recurrent findings, coupled with genetic testing, can enhance diagnostic precision and guide appropriate management strategies for these complex vascular syndromes.

A case report of Klippel–Trenaunay syndrome

This case series highlights the importance of multimodal imaging in distinguishing Klippel-Trenaunay syndrome (KTS) from Parkes Weber syndrome (PWS) and guiding management. Both KTS and PWS are rare congenital vascular disorders characterised by the classic triad of cutaneous vascular malformations, venous varicosities and limb overgrowth. The three cases in this report highlight the spectrum of vascular malformations and their imaging characteristics, emphasising the importance of flow assessment in distinguishing low-flow venous malformations (KTS) from high-flow arteriovenous malformations (PWS). Multimodal cross-sectional imaging is essential for accurate diagnosis and treatment planning in vascular overgrowth syndromes. Contribution: This case series illustrates the critical role of multimodal imaging in differentiating Klippel-Trenaunay syndrome from Parkes Weber syndrome. It emphasizes the distinct imaging findings, particularly vascular flow characteristics, which are essential for accurate diagnosis, guiding appropriate therapeutic interventions, and preventing serious complications.

Is Vascular Malformations in Klippel Trenaunay Syndrome resectable? Treatment by staged excision under certain surgical indications.

Klippel-trenaunay syndrome with multifactorial anemia:successful management with sirolimus

Abstract Introduction/Objective Klippel-Trenaunay syndrome (KTS) is a congenital vascular disorder characterized by capillary malformations and lymphatic/venous anomalies associated with overgrowth of bone/soft tissue. Parkes Weber syndrome (PWS) results in limb hypertrophy and capillary malformations but has the distinct feature of fast-flow arteriovenous connections. Because of the rarity of these syndromes and diverse clinical findings, prognosis is poorly understood. Methods/Case Report To better characterize common manifestations of KTS/PWS seen at autopsy, average patient lifespans, and how KTS/PWS may have ultimately contributed to death, we searched our electronic autopsy database for a 22.5 year span (i.e. 2002-2025). Our hospital is one of the largest tertiary care centers for our state and annually performs 500-575 autopsies. Results Our search yielded 3 cases; in 2 cases decedents had been diagnosed with KTS/PWS. Both were female; age range was 37-42 years. Causes of death included streptococcal sepsis due to cellulitis and pulmonary thromboemboli (PTE) following ventriculoperitoneal shunt revision. Autopsy findings consistent with KTS/PWS included leg hypertrophy, spinal canal syrinx, esotrophia, hemimegacephaly, and scattered vascular proliferations. Conclusion KTS/PWS are rare disorders that can result in many complications including PTE and death. Both can be diagnosed by clinical examination; historically the diagnoses were conflated. Further study is merited.

Background: Lymphatic malformations (LM) are rare congenital vascular anomalies caused by abnormal development and growth of lymphatic vessels. These malformations can lead to a wide range of symptoms, from mild swelling to more severe complications. Treatment options remain limited, especially for complex cases. Recent research has suggested that PIK3CA mutations play a key role in the pathogenesis of LM, potentially offering new possibilities for targeted treatment strategies. Methods: In this study, a cohort of 36 patients diagnosed with LM, Klippel-Trenaunay syndrome (KTS), and Proteus syndrome was analyzed. PIK3CA mutations were assessed in tissue samples obtained from the LM during clinically indicated procedures using digital droplet polymerase chain reaction (ddPCR), targeting five hotspots. Results: PIK3CA mutations were found in 18 patients (50%). The most frequent mutation was p.E542K (c.1624G>A), found in 19.44% of patients, followed by p.H1047R (c.3149A>G), p.E545K (c.1633G>A), and p.H1047L (c.3140A>T) each occurring in 11.11% of the cases. Mutations were more common in isolated LMs, with 63.16% of patients exhibiting PIK3CA mutations. Conclusions: PIK3CA mutations are common in LM, supporting the potential for targeted therapies like PI3K inhibitors in treating complex cases. This research highlights the importance of genetic analysis in the management of LM and offers a new therapeutic approach.

Klippel–Trenaunay syndrome (KTS) is a rare phakomatosis or neurocutaneous syndrome characterized by a triad of cutaneous and visceral hemangiomas, venous varicosities, and soft-tissue or bone hypertrophy. The exact etiology remains unclear, but multiple genetic mutations have been associated with KTS. Recently, the PIK3CA gene has been implicated in its pathogenesis. Here, we report four unique cases of KTS with scoliosis in one case, bilateral nevus of Ota in the second, acroangiodermatitis and scoliosis in the third, and lymphangioma circumscriptum in the fourth.

A bstract Klippel-Trenaunay syndrome (KTS) is a rare congenital condition characterized by cutaneous hemangiomas, varicosities, and hypertrophy of bone or soft tissue, resulting in limb asymmetry. We present a case involving a 13-year-old male who was admitted to Sri Ramachandra Medical College, Chennai, exhibiting headache, vomiting, and drowsiness for six days. A computed tomography (CT) scan indicated obstructive hydrocephalus and vertebrobasilar dolichoectasia. His Glasgow Coma Scale score fell to E2V2M4, necessitating emergency intubation. An urgent right ventriculoperitoneal (VP) shunt was performed, after which he was moved to the intensive care unit for support and antiepileptic medication. Postoperative CT imaging confirmed a well-positioned VP shunt, subarachnoid hemorrhage, and diminished ventricular size. The cardiac evaluation revealed cardiomyopathy with a reduced ejection fraction. Despite inotropic support, hemodynamic stabilization was not achieved. The patient experienced bradycardia and desaturation during resuscitation efforts, ultimately resulting in his death.

Klippel-Trenaunay syndrome (KTS) is a rare congenital vascular disorder associated with somatic mutations in the PIK3CA gene, characterized classically by a triad of capillary malformations, venous malformations, and soft tissue and bone hypertrophy. While KTS commonly involves a single lower extremity, we present an atypical pediatric case featuring extensive venolymphatic malformation of the intergluteal region. This uncommon anatomical localization predisposed the patient to recurrent episodes of cellulitis, significantly complicating clinical management. This case underscores the importance of recognizing atypical presentations of KTS and the heightened susceptibility to recurrent infections, such as cellulitis, which may significantly impact morbidity and patient care.

Capillary malformations updates on aetiopathogenesis, diagnosis, and management.

Background: Klippel-Trenaunay syndrome (KTS) is a congenital vascular malformation syndrome characterized by low-flow vascular anomalies, including venous malformation (VM) and lymphatic involvement. These anomalies may lead to limb asymmetry due to soft tissue and/or bone overgrowth. Compression therapy using elastic garments is considered a conservative and minimally invasive first-line treatment option for KTS. However, the benefits of compression therapy for low-flow vascular malformations, particularly limb VMs, have not been sufficiently evaluated. This prospective, multi-center study assessed the efficacy and safety of compression therapy for KTS with VM. Methods: After measuring the affected limb, a custom-made elastic garment providing 30 mmHg of compression was manufactured (THUASNE, France). A total of 20 patients (7 male, 13 female; mean age: 10.9 years) underwent compression therapy for 26 weeks at four nationwide institutions in Japan. The primary outcome was the change in lower limb circumference. Secondary outcomes included pain, modified Rankin Scale (mRS) score, body water content, vital signs, changes in garment elasticity, and adverse events. Results: All 20 patients completed the study. At the study endpoint, the circumference ratio of the affected to unaffected limbs was significantly reduced at the superior end of the tibial tuberosity (p = 0.02) and the thinnest part of the ankle (p < 0.001). The elastic force of the garment declined by approximately 50% over 26 weeks. No serious adverse events related to the intervention were reported. Conclusions: Compression therapy using a custom-made elastic garment appears to be a safe and effective approach for managing limb overgrowth in patients with KTS and VM. To maintain the therapeutic effect, garment replacement is recommended at least every six months.