Miikka Vikkula

Miikka Vikkula
University of Louvain (UCL), Brussels, Belgium · de Duve Institute

MD, PhD

About

350
Publications
50,165
Reads
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20,101
Citations
Citations since 2016
105 Research Items
9827 Citations
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Introduction
Miikka Vikkula currently works at the de Duve Institute, University of Louvain (UCLouvain), Brussels, Belgium. Miikka does research on Vascular anomalies, Primary lymphedema, Cleft lip and/or palate, and certain cancers. He collaborates with numerous clinicians in Plastic Surgery, Dermatology, Radiology, Clinical Genetics etc. The current projects include: 1) Genetic bases of primary lymphedemas, 2) Genetic bases of cleft lip and/or palate, and 3) Genetic bases of selected cancers. The long-term aims include: better classification and diagnosis, identification of targets for therapy, and generation of models for pre-clinical trials.
Additional affiliations
August 2011 - September 2013
Cliniques Universitaires Saint-Luc
Position
  • Coordinator
February 1997 - present
Université Catholique de Louvain - UCLouvain
Position
  • Professor (Full)
September 1993 - January 1997
Harvard Medical School
Position
  • PostDoc Position

Publications

Publications (350)
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
Objective To study the genotypes and phenotypes of cerebral arteriovenous fistulas that drain or do not drain through the vein of Galen, and true vein of Galen aneurysmal malformations, in order to determine whether genotyping could help improve classification of these malformations and their management. Methods We carried out a retrospective revi...
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
Background: Invasive lobular breast carcinoma (ILC) represents 5 to 15% of all invasive breast cancers (BCs). Here, we aim to investigate inter- and intra-tumor heterogeneity in terms of microenvironment composition, PAM50 molecular classification and proliferation (genomic grade index [GGI]) by combining spatial transcriptomics (ST) and accurate m...
Article
We have created a human chromosomal map of the location of known and candidate genes involved in primary lymphedema (PLE). This should facilitate further discovery and provide a basis for understanding microdeletions which cause lymphedema.
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
Full-text available
Background PIK3CA -related disorders include vascular malformations and overgrowth of various tissues that are caused by postzygotic, somatic variants in the gene encoding phosphatidylinositol-3-kinase (PI3K) catalytic subunit alpha. These mutations result in activation of the PI3K/AKT/mTOR signaling pathway. The goals of this review are to provide...
Article
Lymphoedema is the swelling of one or several parts of the body owing to lymph accumulation in the extracellular space. It is often chronic, worsens if untreated, predisposes to infections and causes an important reduction in quality of life. Primary lymphoedema (PLE) is thought to result from abnormal development and/or functioning of the lymphati...
Article
Fibromuscular dysplasia (FMD), a nonatherosclerotic, noninflammatory disease of medium-sized arteries, is an underdiagnosed disease. We investigated the urinary proteome and developed a classifier for discrimination of FMD from healthy controls and other diseases. We further hypothesized that urinary proteomics biomarkers may be associated with alt...
Article
Full-text available
Fibromuscular dysplasia (FMD) is an arteriopathy associated with hypertension, stroke and myocardial infarction, affecting mostly women. We report results from the first genome-wide association meta-analysis of six studies including 1556 FMD cases and 7100 controls. We find an estimate of SNP-based heritability compatible with FMD having a polygeni...
Article
Full-text available
Extensive lymphatic malformations (LMs) of the head and neck region may require tracheostomy to secure the airway. Treatment of these life-threatening LMs is usually multimodal and includes sclerotherapy and surgery, among others. Recently, systemic therapy with sirolimus has been introduced as an effective treatment for venous and lymphatic malfor...
Article
Primary lymphedema results from the anomalous development of the lymphatic system and typically presents during infancy, childhood, or adolescence. Adult‐onset primary lymphedema is rare and mutations associated with this condition have not been identified. The purpose of this investigation was to search for variants that cause adult‐onset primary...
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
Hypotrichosis‐lymphedema‐telangiectasia syndrome (HLTS) is a rare condition caused by pathogenic variants in the SOX18 gene. SOX18 plays a key role in angio‐ and lymphangiogenesis due to its expression in venous endothelial cells from which the lymphatic system develops. It is also expressed in embryonic hair follicles, heart, and vascular smooth m...
Article
Cleft lip and/or palate are a split in the lip, the palate or both. This results from the inability of lip buds and palatal shelves to properly migrate and assemble during embryogenesis. By extracting primary cells from a cleft patient, we aimed at offering a better understanding of the signaling mechanisms and interacting molecules involved in the...
Article
Full-text available
Enamel renal syndrome (ERS) is a rare recessive disorder caused by loss-of-function mutations in FAM20A (family with sequence similarity 20 member A, OMIM #611062). Enamel renal syndrome is characterized by amelogenesis imperfecta, delayed or failed tooth eruption, intrapulpal calcifications, gingival overgrowth and nephrocalcinosis. Although gingi...
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...
Preprint
Full-text available
Fibromuscular dysplasia (FMD) is an arteriopathy that presents clinically by hypertension and stroke, mostly in early middle-aged women. We report results from the first genome-wide association meta-analysis of FMD including 1962 FMD cases and 7100 controls. We confirmed PHACTR1 and identified three new loci (LRP1, ATP2B1, and LIMA1) associated wit...
Article
COVID-19 is also manifested with hypercoagulability, pulmonary intravascular coagulation, microangiopathy, and venous thromboembolism (VTE) or arterial thrombosis. Predisposing risk factors to severe COVID-19 are male sex, underlying cardiovascular disease, or cardiovascular risk factors including noncontrolled diabetes mellitus or arterial hyperte...
Article
Primary lymphedema is caused by developmental and functional defects of the lymphatic vascular system that result in accumulation of protein-rich fluid in tissues, resulting in edema. The 28 currently known genes causing primary lymphedema can explain <30% of cases. Angiopoietin 1 (ANGPT1) and ANGPT2 function via the TIE1-TIE2 (tyrosine kinase with...
Article
Full-text available
Red blood cell (RBC) deformability is altered in inherited RBC disorders but the mechanism behind this is poorly understood. Here, we explored the molecular, biophysical, morphological, and functional consequences of α-spectrin mutations in a patient with hereditary elliptocytosis (pEl) almost exclusively expressing the Pro260 variant of SPTA1 and...
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
The TSC complex is the cognate GTPase-activating protein (GAP) for the small GTPase Rheb and a crucial regulator of the mechanistic target of rapamycin complex 1 (mTORC1). Mutations in the TSC1 and TSC2 subunits of the complex cause tuberous sclerosis complex (TSC). We present the crystal structure of the catalytic asparagine-thumb GAP domain of TS...
Article
Full-text available
BACKGROUND Biodiversity screens and phylogenetic studies are dependent on reliable DNA sequences in public databases. Biological collections possess vouchered specimens with a traceable history. Therefore, DNA sequencing of samples available at institutional collections can greatly contribute to taxonomy, and studies on evolution and biodiversity....
Article
Objectives The molecular landscape of head and neck squamous cell carcinoma (HNSCC) harbors potentially actionable genomic alterations. We aimed to study the utility of liquid biopsy to (i) characterize the mutational landscape of recurrent/metastatic HNSCC using a comprehensive gene panel and (ii) estimate the concordance between DNA mutations ide...
Article
Full-text available
Background: Multigene panels are routinely used to assess for predisposing germline mutations in families at high breast cancer risk. The number of variants of unknown significance thereby identified increases with the number of sequenced genes. We aimed to determine whether tumor sequencing can help refine the analysis of germline variants based...
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...
Conference Paper
BACKGROUND Breast cancer (BC) is a complex disease. While Mendelian mutations in high-penetrance genes predispose to some familial forms, others are due to multiple common low-penetrance polymorphisms. However, it is unclear if the combination of some rare coding variants has an effect. As some Mendelian forms demonstrate genotype-phenotype correla...
Conference Paper
BACKGROUND Multigene panels are routinely used to search for predisposing mutations in families considered at high risk of breast cancer. The number of variants of unknown significance (VUS) thereby identified increases with the number of sequenced genes. We aimed to determine whether tumor sequencing can help reclassify germline VUS based on secon...
Article
Full-text available
Here, we present first draft genome sequence of the trypanosomatid Herpetomonas muscarum ingenoplastis. This parasite was isolated repeatedly in the black blowfly, Phormia regina, and it forms a phylogenetically distinct clade in the Trypanosomatidae family.
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
Full-text available
Oral clefts are composed of cleft of the lip, cleft of the lip and palate, or cleft of the palate, and they are associated with a wide range of expression and severity. When cleft of the palate is associated with cleft of the lip with preservation of the primary palate, it defines an atypical phenotype called discontinuous cleft. Although this phen...
Preprint
We presented here the first draft genome sequence of the trypanosomatid Herpetomonas muscarum ingenoplastis. This parasite was isolated repeatedly in the black blowfly, Phormia regina. This is the first draft genome of a flagellate from the phylogenetically distinct clade of Trypanosomatidae.
Article
Background Circulating tumor DNA (ctDNA) is a minimally-invasive technique to profile the tumor genome in different cancers but is still underexplored in squamous cell carcinoma of the head and neck (SCCHN). Our aim was to study the relevance of mutational profiling through liquid biopsy in SCCHN. Methods We collected plasma cell-free DNA from 39...
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
Importance Myofibroma is the most frequent fibrous tumor in children. Multicentric myofibroma (referred to as infantile myofibromatosis) is a life-threatening disease. Objective To determine the frequency, spectrum, and clinical implications of mutations in the PDGFRB receptor tyrosine kinase found in sporadic myofibroma and myofibromatosis. Desi...
Article
Full-text available
Background In uveal melanomas, immune infiltration is a marker of poor prognosis. This work intended to decipher the biological characteristics of intra‐tumor immune population, compare it to other established biomarkers and to patients' outcome. Methods Primary, untreated, and mainly large uveal melanomas with retinal detachment were analyzed usi...
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
The neurofibromatoses, which include neurofibromatosis type I (NF1), neurofibromatosis type II (NF2), and schwannomatosis, are a group of syndromes characterized by tumor growth in the nervous system. The RASopathies are a group of syndromes caused by germline mutations in genes that encode components of the RAS/mitogen‐activated protein kinase (MA...
Article
52nd Conference of the European-Society-of-Human-Genetics (ESHG), Gothenburg, SWEDEN, JUN 15-18, 2019
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
Normal vascular development includes the formation and specification of arteries, veins, and intervening capillaries. Vein of Galen malformations (VOGMs) are among the most common and severe neonatal brain arterio-venous malformations, shunting arterial blood into the brain's deep venous system through aberrant direct connections. Exome sequencing...
Article
Mutations in the T‐Box transcription factor gene TBX22 are found in X‐linked Cleft Palate with or without Ankyloglossia syndrome (CPX syndrome). In addition to X‐linked inheritance, ankyloglossia, present in the majority of CPX patients, is an important diagnostic marker, but it is frequently missed or unreported, as it is a “minor” feature. Other...
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.
Article
Background Gene-panels are used to assess predisposition to breast cancer by simultaneous testing of multiple susceptibility genes. This approach increases the identification of variants of unknown significance (VUS) that cannot be used in clinical decision-making. We performed a systematic review of published studies to calculate the prevalence of...