Laurence M Boon

Laurence M Boon
Université Catholique de Louvain - UCLouvain | UCLouvain · Faculty of Medicine and Dentistry

MD, PhD

About

176
Publications
27,188
Reads
How we measure 'reads'
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
13,395
Citations
Citations since 2017
43 Research Items
5511 Citations
201720182019202020212022202302004006008001,000
201720182019202020212022202302004006008001,000
201720182019202020212022202302004006008001,000
201720182019202020212022202302004006008001,000

Publications

Publications (176)
Article
Full-text available
Lymphatic malformations (LMs) are developmental defects of lymphatic vessels. LMs are histologically benign lesions, however, due to localization, size, and unexpected swelling, they may cause serious complications that threaten vital functions such as compression of the airways. A large swelling of the face or neck may also be disfiguring and thus...
Article
Somatic activating Kirsten rat sarcoma viral oncogene homologue (KRAS) mutations have been reported in patients with arteriovenous malformations. By producing LSL-Kras (G12D); Cdh5 (PAC)-CreERT2 [iEC-Kras (G12D*)] mice, we hoped to activate KRAS within vascular endothelial cells (ECs) to generate an arteriovenous malformation mouse model. Neonatal...
Article
Arteriovenous malformations (AVMs) are fast-flow lesions that may be destructive and are the most difficult-to-treat vascular anomalies. Embolization followed by surgical resection is commonly used; however, complete resection is rarely possible and partial resection often leads to dramatic worsening. Accumulating data implicate abnormal angiogenic...
Article
Background and purpose: Sturge-Weber syndrome (SWS) is a neurocutaneous disorder characterized by clinical manifestations involving the brain, eye and skin. SWS is commonly caused by somatic mutations in G protein subunit Alpha Q (GNAQ). Five cases of subunit Alpha 11 (GNA11) mutations have been reported. We studied phenotypic features of GNA11-SW...
Article
Vascular Anomalies are a heterogenous group of vascular lesions that can be divided, according to the International Society for the Study of Vascular Anomalies Classification, into two main groups : Vascular Tumors and Vascular Malformations. Vascular Malformations can be further subdivided into slow‐flow and fast‐flow malformations. This clinical...
Article
Full-text available
The European Reference Network on Rare Multisystemic Vascular Diseases (VASCERN), is dedicated to gathering the best expertise in Europe and provide accessible cross-border healthcare to patients with rare vascular diseases. Infantile Hemangiomas (IH) are benign vascular tumors of infancy that rapidly growth in the first weeks of life, followed by...
Article
Central conducting lymphatic anomaly (CCLA), characterized by the dysfunction of core collecting lymphatic vessels including the thoracic duct and cisterna chyli, and presenting as chylothorax, pleural effusions, chylous ascites, and lymphedema, is a severe disorder often resulting in fetal or perinatal demise. Although pathogenic variants in RAS/m...
Article
Full-text available
Background Hydrops fetalis, a pathological fluid accumulation in two or more body compartments, is aetiologically heterogeneous. We investigated a consanguineous family with recurrent pregnancy loss due to severe early-onset non-immune hydrops fetalis. Methods and results Whole exome sequencing in four fetuses with hydrops fetalis revealed that th...
Article
Full-text available
Background Theragnostic management, treatment according to precise pathological molecular targets, requests to unravel patients’ genotypes. We used targeted next-generation sequencing (NGS) or digital droplet polymerase chain reaction (ddPCR) to screen for somatic PIK3CA mutations on DNA extracted from resected lesional tissue or lymphatic endothel...
Article
Lymphatic vessels maintain tissue fluid homeostasis by returning to blood circulation interstitial fluid that has extravasated from the blood capillaries. They provide a trafficking route for cells of the immune system, thus critically contributing to immune surveillance. Developmental or functional defects in the lymphatic vessels, their obstructi...
Article
Vascular and lymphatic malformations represent a challenge for clinicians. The identification of inherited and somatic mutations in important signaling pathways, including the PI3K (phosphoinositide 3-kinase)/AKT (protein kinase B)/mTOR (mammalian target of rapamycin), RAS (rat sarcoma)/RAF (rapidly accelerated fibrosarcoma)/MEK (mitogen-activated...
Article
Full-text available
Gorham-Stout disease (GSD) is a sporadically occurring lymphatic disorder. Patients with GSD develop ectopic lymphatic vessels in bone, gradually lose bone, and can have life-threatening complications such as chylothorax. The etiology of GSD is poorly understood and current treatments for this disease are inadequate for most patients. To explore th...
Article
Vascular anomalies are developmental defects of the vasculature and encompass a variety of disorders. The identification of genes mutated in the different malformations provides insight into the etiopathogenic mechanisms and the specific roles the associated proteins play in vascular development and maintenance. A few familial forms of vascular ano...
Chapter
Vascular malformations arise as a consequence of aberrant regulation of the establishment and maintenance of localized vasculature. Though the majority of vascular anomalies form sporadically, the rare familial cases expedited understanding the pathogenesis of vascular anomalies. The identification of genes that have been mutated identified the sig...
Article
Vascular malformations are inborn errors of vascular morphogenesis and consist of localized networks of abnormal blood and/or lymphatic vessels with weak endothelial cell proliferation. They have historically been managed by surgery and sclerotherapy. Extensive insight into the genetic origin and molecular mechanism of development has been accumula...
Article
Full-text available
Lymphatic malformations (LMs) are debilitating vascular anomalies presenting with large cysts (macrocystic) or lesions that infiltrate tissues (microcystic). Cellular mechanisms underlying LM pathology are poorly understood. Here we show that the somatic PIK3CAH1047R mutation, resulting in constitutive activation of the p110α PI3K, underlies both m...
Article
Vascular malformations are subdivided into capillary, lymphatic, venous, arteriovenous, and mixed malformations, according to the type of affected vessels. Until a few years ago, treatment options were limited to sclerotherapy and/or surgery. Since, it has been demonstrated that the majority of vascular malformations are caused by inherited or soma...
Article
Full-text available
Objectives: Infantile hemangiomas (IHs) are common; some cases require timely referral and treatment to prevent complications. We developed and validated a reliable instrument for timely and adequate referral of patients with IH to experts by nonexpert primary physicians. Methods: In this multicenter, cross-sectional, observational study, we use...
Chapter
Vascular malformations are caused by developmental errors that occur in utero. They can be localized or diffuse and occur in any body part, including the viscera. Some are inconsequential, whereas others cause cosmetic problems, functional disability or threaten life. Clinical features permit diagnosis in about 90% of superficial vascular malformat...
Article
Objective: Arteriovenous Malformations (AVMs) have an inherent capacity to form new blood vessels resulting in excessive lesion growth and this is further triggered by the release of angiogenic factors. Gallium-68 (68Ga) labeled arginine-glycine-aspartate tripeptide sequence (RGD) positron emission tomography (PET)/computed tomography (CT) imaging...
Article
Background Capillary malformation-arteriovenous malformation is an autosomal dominant disorder, characterised by capillary malformations and increased risk of fast-flow vascular malformations, caused by loss-of-function mutations in the RASA1 or EPHB4 genes. Around 25% of the patients do not seem to carry a germline mutation in either one of these...
Article
Full-text available
There is a variety of outcome reporting in the clinical research on peripheral vascular malformations including capillary, venous, lymphatic, arteriovenous and combined malformations. Without harmonization of outcome measures, treatments cannot be properly compared. This hampers the development of evidence‐based treatment guidelines, urgently neede...
Article
Purpose of review: The field of vascular anomalies has seen a fundamental change during the past 10 years. The identification of somatic genetic mutations as the explanation of sporadic vascular anomalies opened the doors to study prospectively and a posteriori the causes of various vascular malformations. This was helped by the rapidly evolving g...
Article
51st Conference of the European-Society-of-Human-Genetics (ESHG) in conjunction with the European Meeting on Psychosocial Aspects of Genetics (EMPAG), Milan, ITALY, JUN 16-19, 2018
Article
Full-text available
Background Extensive and complex vascular malformations often cause chronic pain and severe functional restraint. Conventional treatments, such as surgery and/or sclerotherapy, are rarely curative, underscoring the great need for new therapeutic modalities. Recent preclinical and clinical data demonstrated that sirolimus could offset the progressio...
Article
Introduction L’hémangiome infantile (HI) est la tumeur bénigne la plus fréquente du nourrisson. Son évolution naturelle est habituellement la régression spontanée. Certaines formes compliquées peuvent entraîner douleur, dysfonction d’un organe, défiguration permanente, voire une altération des fonctions vitales dans les cas les plus graves. Un ques...
Article
We herein report the case of a 3‐year‐old girl with atypical congenital right upper limb lymphedema who developed an angiosarcoma. Only a few cases have been reported following congenital form of lymphedema and only 4 in such a young child. We also summarize all cases of angiosarcoma associated with congenital lymphedema reported in the literature.
Chapter
Vascular anomalies are separated into vascular tumours and vascular malformations. Vascular malformations are named according to the affected type of vessels, that is venous, capillary, arteriovenous or lymphatic malformations. Up to now, sclerotherapy, embolisation and/or surgery are the treatments of choice, yet they do not often offer a curative...
Article
The detection of somatic, activating genetic mutations to underlie development of vascular tumors and malformations led to a better understanding of their pathophysiology. Proteins encoded by the detected mutated genes activate the two major signaling pathways, also involved in cancer: the RAS/MAPK/ERK pathway and/or the PI3K/AKT/mTOR pathway. This...
Article
Venous malformations (VMs) of the head and neck arise from deficits in the development of venous network. Clinically, VMs are highly variable, from small and asymptomatic varicosities to massive cervicofacial lesions. Therapeutic approaches include surgery; laser photocoagulation; sclerotherapy; and, more recently, systemic targeted drugs. This art...
Article
外周血管畸形(VM)是指由在胚胎中形成的血管发育缺陷而导致的胎记或肿胀。不同的类型可根据其主要组成部分来分类:分为淋巴管(LM)、血管(VM)或结合动脉和血管(AVM)。目前难以评估现有的各种医疗和外科手术治疗方法,因为医学界尚没有衡量结果指标的统一方法。该国际组织针对医务人员和患者开展了一项在线调查,以决定未来的临床试验中需要重点记录的因素。他们首先列出了病情及其疗法的各种方面,涉及36个领域共97个具体项目。随后,他们邀请了167名医生和134名患者及患者父母对这些项目进行打分,从0(不重要)到4(至关重要)。经过3轮调查和共识会议之后,选项范围逐渐缩小。最终达成一致的“核心指标集”涵盖:扫描结果;医生对由VM压力引起的问题的评估;患者或父母对症状、疼痛和生活质量的评估;以及他们对治疗、...
Chapter
Lymphatic malformations (LMs) are due to localized defects in lymphatic development. They usually occur sporadically. There is an important heterogeneity in clinical presentations. LMs can affect any part of the body, be isolated, or be part of a syndrome. They can present as pure or combined lesions. Lymphaticovenous malformation (LVM) is a common...
Article
Full-text available
Background: An important limitation in vascular malformation research is the heterogeneity in outcome measures used for the evaluation of treatment outcome. Objective: The Outcome measures for VAscular MAlformations (OVAMA) project aimed to reach international consensus on a core outcome set (COS) for clinical research on peripheral vascular mal...
Article
Vascular anomalies arise as a consequence of improper development and maintenance of the vasculature. Our knowledge on the pathophysiological bases of vascular anomalies has skyrocketed during the past 5 years. It is becoming clear that common intracellular signaling pathways are often activated by mutations, causing endothelial cell dysfunction. T...
Chapter
Arteriovenous malformations (AVMs) and arteriovenous fistulas (AVFs) are abnormal fast-flow connections between arterial and venous circulation, without a normal intervening capillary bed. They are congenital developmental lesions seen in various sites of the body. Pathogenesis is still largely unknown, and no specific biomarkers have been identifi...
Article
Full-text available
Background: Most arteriovenous malformations (AVMs) are localized and occur sporadically. However, they also can be multifocal in autosomal-dominant disorders, such as hereditary hemorrhagic telangiectasia and capillary malformation (CM)-AVM. Previously, we identified RASA1 mutations in 50% of patients with CM-AVM. Herein we studied non-RASA1 pati...
Article
Vascular anomalies (VAs) result from the defective development of the embryonic vascular system and feature dysplastic malformed vessels, which are not always apparent at birth. They do not regress over the patient's lifetime; they usually have commensurate growth during childhood and may worsen over time if not treated. VAs may cause chronic painf...
Article
Les malformations veineuses se caracterisent par des ectasies veineuses avec une deficience relative en muscle lisse. Elles sont souvent responsables de deformation, douleur, coagulopathie et saignement. Malgre des sclerotherapies recidivantes et des resections chirurgicales, les recidives sont frequentes. La rapamycine est un inhibiteur de mTor qu...
Article
Les anomalies vasculaires, plus communément appelées « angiomes », représentent une pathologie rare et fréquemment méconnue du monde médical. Elles peuvent être divisées en deux catégories distinctes dont le pronostic et la prise en charge sont radicalement différents : les tumeurs vasculaires et les malformations vasculaires. Leur identification p...
Article
Full-text available
Importance Infantile hemangiomas involute to some extent, but they often leave sequelae that may cause disfigurement. Factors determining the risk of permanent sequelae after regression are of crucial importance in treatment decision making. Objectives To describe the sequelae left by infantile hemangiomas after natural involution and to identify...
Article
Full-text available
Blue Rubber Bleb Nevus syndrome (Bean syndrome, BRBN) is a rare, severe disorder of unknown cause, characterized by numerous cutaneous and internal venous malformations (VMs); gastrointestinal lesions are pathognomonic. We discovered somatic mutations in TEK, the gene encoding TIE2, in 15 of 17 individuals with BRBN. Somatic mutations were also ide...
Chapter
Chapters provides overview of pathways of development and reviews of dysmorphic syndromes for which the causative gene has been identified. For each disorder, an analysis of the role of the gene in the relevant developmental pathway is provided, along with the mechanism by which mutations in the gene cause the developmental pathology. Emphasis is p...
Chapter
RASA1 encodes P120RASGTPase-activating protein (P120RASGAP), a small intracellular protein, involved in RAS regulation. Mutations in this gene result in capillary malformation–arteriovenous malformation (CM–AVM; OMIM 608354), an autosomal dominant disorder (Eerola et al., 2003) with high penetrance and variable expressivity. Small, multifocal and r...
Chapter
Chapters provides overview of pathways of development and reviews of dysmorphic syndromes for which the causative gene has been identified. For each disorder, an analysis of the role of the gene in the relevant developmental pathway is provided, along with the mechanism by which mutations in the gene cause the developmental pathology. Emphasis is p...
Article
Full-text available
Background and objectives: Propranolol is first-line therapy for problematic infantile hemangiomas (IHs). Rebound growth after propranolol discontinuation is noted in 19% to 25% of patients. Predictive factors for rebound are not completely understood and may alter the management approach. The goal of the study was to describe a cohort of patients...
Article
Background: There is limited information regarding early development of soft-tissue and/or bone hypertrophy with facial port-wine stains (PWS). Objective: We sought to characterize patients with hypertrophic PWS presenting during childhood. Methods: Patients with a facial PWS and underlying hypertrophy that developed before the age of 18 years...
Article
Les traitements médicaux ont progressivement trouvé leur place dans la prise en charge des hémangiomes et des malformations vasculaires afin, soit d’en accélérer la régression (hémangiome), soit de réduire la fréquence des complications (malformations vasculaires). Les bêta-bloquants ne sont plus discutés dans certaines localisations d’hémangiomes...
Chapter
Vascular malformations are errors of development of vessels that occur during embryogenesis. They are rheologically divided into slow-flow (capillary, lymphatic, venous and combined) and fast-flow (arterial, arteriovenous, and combined) malformations. These congenital lesions grow proportionally with the patient and never spontaneously regress.Veno...
Article
Introduction Certains angiomes plans comportent une hypertrophie tissulaire précoce différente de l’hypertrophie cutanée des « angiomes plans vieillis ». Leur profil évolutif et la réponse thérapeutique semblent spécifiques. L’objectif de cette étude était d’évaluer les caractéristiques cliniques des angiomes plans précocement hypertrophiques du vi...
Article
Full-text available
PDF : http://www.cell.com/ajhg/abstract/S0002-9297(15)00456-5# Somatic mutations in TEK, the gene encoding endothelial cell tyrosine kinase receptor TIE2, cause more than half of sporadically occurring unifocal venous malformations (VMs). Here, we report that somatic mutations in PIK3CA, the gene encoding the catalytic p110α subunit of PI3K, caus...
Article
Diffuse venous malformations can be associated with a consumptive coagulopathy characterized by a reduction of fibrinogen level, platelet count and elevated D-dimer level. We report a case of a patient with extensive venous malformations, hemorrhagic symptoms and biological signs of intravascular coagulopathy. She was initially treated effectively...
Article
Full-text available
Venous malformations (VMs) are localized defects in vascular morphogenesis frequently caused by mutations in the gene for the endothelial tyrosine kinase receptor TIE2. Here, we report the analysis of a comprehensive collection of twenty-two TIE2 mutations identified in patients with VM, either as single amino acid substitutions or as double-mutati...
Article
Full-text available
Venous malformations (VMs) are composed of ectatic veins with scarce smooth muscle cell coverage. Activating mutations in the endothelial cell tyrosine kinase receptor TIE2 are a common cause of these lesions. VMs cause deformity, pain, and local intravascular coagulopathy, and they expand with time. Targeted pharmacological therapies are not avail...
Data
Full-text available
Background Microcephaly with or without chorioretinopathy, lymphedema, or mental retardation syndrome (MCLMR) is a rare autosomal dominant disorder with variable expressivity. It is characterized by mild-to-severe microcephaly, often associated with intellectual disability, ocular defects and lymphedema. It can be sporadic or inherited. Eighty-seve...
Article
Full-text available
With a prevalence of 2.6-4.5 %, infantile haemangiomas (IH) represent the most common tumour of infancy. While the majority of IH does not require therapy and regresses spontaneously, about 10 % of IH exhibit complications such as obstruction, ulceration or disfigurement. With the advent of oral propranolol, many conventional treatment options have...
Article
Full-text available
Microcephaly with or without chorioretinopathy, lymphedema, or mental retardation syndrome (MCLMR) is a rare autosomal dominant disorder with variable expressivity. It is characterized by mild-to-severe microcephaly, often associated with intellectual disability, ocular defects and lymphedema. It can be sporadic or inherited. Eighty-seven patients...
Article
To assess the efficacy of surgical treatment of intra-articular knee venous malformations (VM). Between 1998 and 2010, 8 children (mean age: 12.3 y) underwent surgical resection of their vascular malformation (7 venous and 1 capillary venous) involving the knee joint. The lesion was diffuse in 6 cases and well-demarcated in 2 cases. All children we...
Article
Malformation affecting the genital tract is a rare condition. Enlargement of the mass and specific complications may occur following hemodynamic changes associated with pregnancy. A 25-year-old pregnant primigravida affected by an extended vulvar and thigh venous malformation with localised intravascular consumptive coagulopathy was referred to our...
Chapter
For this chapter, an extensive review of the literature regarding the genes and clinical presentations associated with primary lymphedema is performed. All the signs that have been mentioned for the patients with a proven mutation are catalogued. The phenotypes are divided into two groups depending on whether lymphedema is a primary or a secondary...
Article
Maffucci syndrome (MS) is a rare congenital disorder characterized by multiple central cartilaginous tumors (enchondromas) in association with cutaneous spindle cell hemangiomas. These patients have a high incidence of malignant transformation. No familial case is known and the etiopathogenic cause remains unknown. In enchondromatosis (Ollier disea...
Article
Full-text available
Lymphatic anomalies include a variety of developmental and/or functional defects affecting the lymphatic vessels: sporadic and familial forms of primary lymphedema, secondary lymphedema, chylothorax and chylous ascites, lymphatic malformations, and overgrowth syndromes with a lymphatic component. Germline mutations have been identified in at least...
Article
Venous malformations are the most frequent lesions seen in interdisciplinary vascular anomaly centers, due to the pain, esthetic problems, and functional difficulties that are associated with their size and/or localization in different organs. In this chapter, we review the clinical features and genetic background of inherited glomuvenous malformat...
Article
Capillary malformation is the most frequent vascular malformation, occurring in 0.3% of newborns. It is usually a sporadic and isolated lesion, but can also be seen as part of a syndrome, such as Sturge–Weber syndrome and macrocephaly–capillary malformation syndrome. Familial forms exist, and in those cases the capillary malformations are most ofte...
Article
Full-text available
Lymphedema is caused by dysfunction of lymphatic vessels, leading to disabling swelling that occurs mostly on the extremities. Lymphedema can be either primary (congenital) or secondary (acquired). Familial primary lymphedema commonly segregates in an autosomal dominant or recessive manner. It can also occur in combination with other clinical featu...
Article
Capillary malformation-arteriovenous malformation (CM-AVM) is an autosomal dominant disorder, caused by heterozygous RASA1 mutations, and manifesting multifocal capillary malformations and high risk for fast-flow lesions. A limited number of patients has been reported, raising the question of the phenotypic borders. We identified new patients with...
Article
Full-text available
Mutations in the endothelial cell tyrosine kinase receptor TIE2 cause inherited and sporadic forms of venous malformation. The recurrent somatic mutation L914F and common germline mutation R849W differ in terms of phosphorylation-level, as well as sub-cellular localization and trafficking of the receptor. Previous studies have shed light on certain...