Article
Critical Care Medicine
Mithum Kularatne, Melanie Eyries, Laurent Savale, Marc Humbert, David Montani
Summary: Heritable pulmonary arterial hypertension (PAH) is often associated with pathogenic variants of BMPR2. This study describes two patients with pulmonary arteriovenous malformations (AVMs) who were found to carry variants of BMPR2 through gene sequencing. Through these cases and understanding of the BMP9 pathway, it is suggested that BMPR2 variants may increase the risk of pulmonary AVMs.
Review
Clinical Neurology
Karan K. Topiwala, Smit D. Patel, Jeffrey L. Saver, Christopher D. Streib, Claire L. Shovlin
Summary: Covert pulmonary arteriovenous malformations (PAVMs) have the potential to cause early onset, preventable ischemic strokes, occurring a decade earlier than routine strokes with high prevalence rates according to large-scale thoracic CT screens. Treatment options such as single antiplatelet therapy may be effective for secondary prophylaxis, but require nuanced risk-benefit analysis.
Review
Cell Biology
S. Krithika, S. Sumi
Summary: Brain arteriovenous malformations (bAVM) are congenital or sporadic focal lesions with a significant risk of intracerebral hemorrhage, and individual differences exist in their onset, progression, and severity. Research supports the involvement of localized inflammation in bAVM disease progression, which is orchestrated by genetic moderators and inflammatory mediators. Targeting the inflammatory processes and mediators may offer potential therapies for the treatment of brain AVM, opening up new avenues for causal therapy.
JOURNAL OF CELLULAR PHYSIOLOGY
(2021)
Article
Radiology, Nuclear Medicine & Medical Imaging
Demetrios A. Raptis, Ryan Short, Caroline Robb, Joshua Marlow, Muhammad Naeem, Sebastian McWilliams, Andrew J. White, Murali Chakinala, Daniel Picus, Sanjeev Bhalla
Summary: A pulmonary arteriovenous malformation (PAVM) is an abnormal connection between a pulmonary artery and a pulmonary vein, resulting in a right-to-left shunt. Diagnosing and distinguishing PAVMs from their mimics is crucial for treatment and prevention of complications.
Article
Cardiac & Cardiovascular Systems
Hyojin Park, Jessica Furtado, Mathilde Poulet, Minhwan Chung, Sanguk Yun, Sungwoon Lee, William C. Sessa, Claudio A. Franco, Martin A. Schwartz, Anne Eichmann
Summary: This study demonstrates the critical role of ALK1 in controlling endothelial cell polarization against blood flow direction and promoting vein-to-artery migration, while identifying integrin-YAP/TAZ signaling blockers as potential targets for preventing vascular malformations in patients with hereditary hemorrhagic telangiectasia.
Article
Clinical Neurology
Lea Scherschinski, Redi Rahmani, Visish M. Srinivasan, Joshua S. Catapano, S. Paul Oh, Michael T. Lawton
Summary: Brain arteriovenous malformations (AVMs) are high-pressure, low-resistance vascular structures with a risk of spontaneous rupture. Understanding the cellular and molecular pathways can help prevent their development and progression. Treatment options are diverse and often involve a multidisciplinary approach, with an increasing demand for pharmacologic interventions.
WORLD NEUROSURGERY
(2022)
Article
Multidisciplinary Sciences
Young-Ok Na, Hwa Kyung Park, Jae-Kyeong Lee, Bo-Gun Kho, Tae-Ok Kim, Hong-Joon Shin, Yong-Soo Kwon, Yu-Il Kim, Sung-Chul Lim, Hyung-Joo Oh, Cheol-Kyu Park, In-Jae Oh, Young-Chul Kim, Ha-Young Park
Summary: Older age (>= 65 years) is a risk factor for the development of cerebral complications in patients with PAVMs. Therefore, treatment should be considered in older patients with PAVMs.
Review
Biochemistry & Molecular Biology
Katharina Schimmel, Md Khadem Ali, Serena Y. Tan, Joyce Teng, Huy M. Do, Gary K. Steinberg, David A. Stevenson, Edda Spiekerkoetter
Summary: Arteriovenous malformations are vascular anomalies that are typically present at birth and involve an abnormal direct connection between an artery and a vein, bypassing capillaries. These lesions can have significant implications and the therapeutic options are limited. There are still many knowledge gaps in the field that need to be addressed for the successful development of therapeutic strategies in the future.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Critical Care Medicine
J. Hessels, S. Kroon, V. V. M. Vorselaars, S. Boerman, J. J. Mager, M. C. Post
Summary: Pulmonary arteriovenous malformations (PAVMs) are direct connections between the pulmonary artery and the pulmonary vein, mostly associated with hereditary hemorrhagic telangiectasia (HHT). PAVMs can lead to severe neurologic complications such as stroke and brain abscess. Screening for PAVMs using transthoracic contrast echocardiography (TTCE) is recommended, with a rescreening interval of 5 years.
Article
Radiology, Nuclear Medicine & Medical Imaging
S. Kroon, D. A. F. van den Heuvel, J. A. Vos, M. van Leersum, M. J. L. van Strijen, M. C. Post, J. J. Mager, R. J. Snijder
Summary: There are differences in clinical and radiographic characteristics between idiopathic and hereditary HHT-associated PAVMs. However, the outcomes of embolotherapy are comparable, suggesting similar treatment and follow-up approaches should be taken for both groups.
CLINICAL RADIOLOGY
(2021)
Article
Clinical Neurology
Jacob Bodilsen, Trine Madsen, Christian Thomas Brandt, Katrine Mullertz, Lothar Wiese, Semra Turan Demirci, Hannah Elena Suhrs, Lykke Larsen, Sabine Ute Alice Gill, Birgitte Ronde Hansen, Brian Nilsson, Lars Haukali Omland, Emil Fosbol, Anette Drohse Kjeldsen, Henrik Nielsen
Summary: This study aimed to determine the prevalence of pulmonary arteriovenous malformations (PAVMs) among survivors of brain abscess and assessed the proportion of cardiac right-to-left shunts. The study found that undiagnosed PAVM among adult survivors of cryptogenic bacterial brain abscess is rare but should be considered in select patients. The prevalence of cardiac right-to-left shunts among brain abscess patients corresponds to the prevalence in the general population.
EUROPEAN JOURNAL OF NEUROLOGY
(2023)
Article
Health Care Sciences & Services
Salim A. Si-Mohamed, Alexandra Cierco, Delphine Gamondes, Lauria Marie Restier, Laura Delagrange, Vincent Cottin, Sophie Dupuis-Girod, Didier Revel
Summary: Embolization with Onyx (R) for recurrent pulmonary arteriovenous malformations (PAVMs) in hereditary hemorrhagic telangiectasia (HHT) showed satisfactory short- and long-term safety and efficacy, with an immediate occlusion rate of 100% and a long-term rate of 60%.
JOURNAL OF PERSONALIZED MEDICINE
(2022)
Review
Respiratory System
William Salibe-Filho, Francini Rossetto de Oliveira, Mario Terra-Filho
Summary: This review provides an overview of pulmonary arteriovenous malformations (PAVMs), including their clinical, radiological presentations, investigation, and treatment options. PAVMs are mainly caused by hereditary hemorrhagic telangiectasia (HHT), also known as RenduOsler-Weber syndrome. Epistaxis evaluation is important for patients with repeated nosebleeds, anemia, and hypoxemia symptoms. Contrast echocardiography and chest CT are crucial for evaluating PAVMs. Embolization is the preferred treatment, especially for patients with hypoxemia or to prevent systemic infections. Disease management in special conditions like pregnancy and regular CT follow-up are also discussed. Knowledge of PAVMs by healthcare professionals is crucial for early diagnosis and potentially altering the disease's natural course.
JORNAL BRASILEIRO DE PNEUMOLOGIA
(2023)
Article
Clinical Neurology
Chul Han, Michael J. Lang, Candice L. Nguyen, Ernesto Luna Melendez, Shwetal Mehta, Gregory H. Turner, Michael T. Lawton, S. Paul Oh
Summary: This study developed a mouse model with a genetics-based approach to replicate the anatomy, hemodynamics, and microhemorrhagic behavior of brain arteriovenous malformations (AVMs). The model provides a novel experimental platform for future studies on the pathophysiology, growth, rupture, and therapeutic regression of AVMs.
JOURNAL OF NEUROSURGERY
(2022)
Review
Genetics & Heredity
Hiroki Hongo, Satoru Miyawaki, Yu Teranishi, Daiichiro Ishigami, Kenta Ohara, Yu Sakai, Daisuke Shimada, Motoyuki Umekawa, Satoshi Koizumi, Hideaki Ono, Hirofumi Nakatomi, Nobuhito Saito
Summary: Cerebrovascular malformations are abnormal development of cerebral vasculature that can lead to hemorrhagic stroke, seizures, and neurological defects. The most common forms are brain arteriovenous malformations and cerebral cavernous malformations, which can occur both sporadically and in inherited forms. Molecular genetic methodologies have helped to identify causative or associated genes.
JOURNAL OF HUMAN GENETICS
(2023)
Article
Genetics & Heredity
Jessica M. Clarke, Mary Alikian, Sihao Xiao, Dalia Kasperaviciute, Ellen Thomas, Isobel Turbin, Kike Olupona, Elna Cifra, Emanuel Curetean, Teena Ferguson, Julian Redhead, Claire L. Shovlin
JOURNAL OF MEDICAL GENETICS
(2020)
Article
Hematology
Claire L. Shovlin, Ilenia Simeoni, Kate Downes, Zoe C. Frazer, Karyn Megy, Maria E. Bernabeu-Herrero, Abigail Shurr, Jennifer Brimley, Dilipkumar Patel, Loren Kell, Jonathan Stephens, Isobel G. Turbin, Micheala A. Aldred, Christopher J. Penkett, Willem H. Ouwehand, Luca Jovine, Ernest Turro
Letter
Emergency Medicine
Claire L. Shovlin, Marcela P. Vizcaychipi
EMERGENCY MEDICINE JOURNAL
(2020)
Article
Genetics & Heredity
Omer F. Eker, Edoardo Boccardi, Ulrich Sure, Maneesh C. Patel, Saverio Alicante, Ali Alsafi, Nicola Coote, Freya Droege, Olivier Dupuis, Annette Dam Fialla, Bryony Jones, Ujwal Kariholu, Anette D. Kjeldsen, David Lefroy, Gennaro M. Lenato, Hans Jurgen Mager, Guido Manfredi, Troels H. Nielsen, Fabio Pagella, Marco C. Post, Catherine Rennie, Carlo Sabba, Patrizia Suppressa, Pernille M. Toerring, Sara Ugolini, Elisabetta Buscarini, Sophie Dupuis-Girod, Claire L. Shovlin
ORPHANET JOURNAL OF RARE DISEASES
(2020)
Article
Medicine, General & Internal
C. L. Shovlin, M. P. Vizcaychipi
Summary: COVID-19 presents more systemic complications and severe pulmonary vasculopathy compared to other respiratory viruses, which may be related to the sustained downregulation of ACE2 protein expression after SARS-CoV-2 infection. Research has shown that the ACE2 gene is located in a novel cluster on the X chromosome that is co-regulated with other genes. Failure to rapidly suppress viral replication in patients predicts delayed responses that may contribute to deteriorations.
QJM-AN INTERNATIONAL JOURNAL OF MEDICINE
(2023)
Article
Clinical Neurology
Karan K. Topiwala, Smit D. Patel, Mubashir Pervez, Claire L. Shovlin, Mark J. Alberts
Summary: Pulmonary arteriovenous fistulas (PAVFs) are a treatable cause of acute ischemic stroke, possibly related to hereditary hemorrhagic telangiectasia. Patients with PAVF are younger, have lower inpatient morbidity and case fatality rates, and exhibit several independent risk markers for AIS.
Article
Genetics & Heredity
Srimmitha Balachandar, Tamara J. Graves, Anika Shimonty, Katie Kerr, Jill Kilner, Sihao Xiao, Richard Slade, Manveer Sroya, Mary Alikian, Emanuel Curetean, Ellen Thomas, Vivienne P. M. McConnell, Shane McKee, Freya Boardman-Pretty, Andrew Devereau, Tom A. Fowler, Mark J. Caulfield, Eric W. Alton, Teena Ferguson, Julian Redhead, Amy J. McKnight, Geraldine A. Thomas, Micheala A. Aldred, Claire L. Shovlin
Summary: Hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal dominant vascular dysplasia caused by mutations in ACVRL1, ENG, or SMAD4 genes. A novel GDF2 variant has been identified in HHT patients with pulmonary AVMs, suggesting a new association between GDF2 mutations and HHT.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2022)
Article
Genetics & Heredity
Connor D. Davieson, Katie E. Joyce, Lakshya Sharma, Claire L. Shovlin
Summary: The study tested new recommendations from the ClinGen Sequence Variant Interpretation Working Group and found that the new rules have a significant impact on determining pathogenicity. Based on the results, it is suggested to adjust existing rules for pathogenic gene variants associated with specific diseases to improve accuracy.
EUROPEAN JOURNAL OF MEDICAL GENETICS
(2021)
Article
Genetics & Heredity
C. L. Shovlin, E. Buscarini, C. Sabba, H. J. Mager, A. D. Kjeldsen, F. Pagella, U. Sure, S. Ugolini, P. M. Torring, P. Suppressa, C. Rennie, M. C. Post, M. C. Patel, T. H. Nielsen, G. Manfredi, G. M. Lenato, D. Lefroy, U. Kariholu, B. Jones, A. D. Fialla, O. F. Eker, O. Dupuis, F. Droege, N. Coote, E. Boccardi, A. Alsafi, S. Alicante, S. Dupuis-Girod
Summary: Hereditary haemorrhagic telangiectasia (HHT) is a complex vascular disease affecting 85,000 European citizens. The European Reference Network established a working group dedicated to HHT, providing expert care and treatment standards for HHT patients.
EUROPEAN JOURNAL OF MEDICAL GENETICS
(2022)
Review
Clinical Neurology
Karan K. Topiwala, Smit D. Patel, Jeffrey L. Saver, Christopher D. Streib, Claire L. Shovlin
Summary: Covert pulmonary arteriovenous malformations (PAVMs) have the potential to cause early onset, preventable ischemic strokes, occurring a decade earlier than routine strokes with high prevalence rates according to large-scale thoracic CT screens. Treatment options such as single antiplatelet therapy may be effective for secondary prophylaxis, but require nuanced risk-benefit analysis.
Article
Respiratory System
Emily Anderson, Lakshya Sharma, Ali Alsafi, Claire L. Shovlin
Summary: For patients with pulmonary arteriovenous malformations (PAVMs), enhanced clinical suspicion and genetic testing for hereditary hemorrhagic telangiectasia (HHT) is recommended, even in the absence of significant features of HHT.
Article
Hematology
Katie E. Joyce, Ebun Onabanjo, Sheila Brownlow, Fadumo Nur, Kike Olupona, Kehinde Fakayode, Manveer Sroya, Geraldine A. Thomas, Teena Ferguson, Julian Redhead, Carolyn M. Millar, Nichola Cooper, D. Mark Layton, Freya Boardman-Pretty, Mark J. Caulfield, Genomics England Res Consortium, Clarire L. Shovlin
Summary: Patients with HHT commonly have rare variants in genes relevant to their phenotype, offering new therapeutic targets and opportunities for personalized medicine strategies.
Article
Genetics & Heredity
Sophie Dupuis-Girod, Claire L. Shovlin, Anette D. Kjeldsen, Hans-Jurgen Mager, Carlo Sabba, Freya Droege, Anne-Emmanuelle Fargeton, Annette D. Fialla, Silvia Gandolfi, Ruben Hermann, Gennaro M. Lenato, Guido Manfredi, Marco C. Post, Catherine Rennie, Patrizia Suppressa, Ulrich Sure, Elisabetta Buscarini
Summary: Hereditary haemorrhagic telangiectasia (HHT) is a rare vascular disease that causes nosebleeds, anemia, and organ malformations. The treatment for HHT is diverse, and one option is intravenous bevacizumab.
EUROPEAN JOURNAL OF MEDICAL GENETICS
(2022)
Letter
Hematology
Claire L. Shovlin, Dilip Patel, Adrianna Bielowka, Jonathan A. Ledermann, Atieh Modarresi, Maria E. Genomics England Res Consortium, Maria E. Bernabeu-Herrero, Micheala A. Aldred, Ali Alsafi
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Article
Genetics & Heredity
Claire L. Shovlin, Fatma Almaghlouth, Ali Alsafi, Nicola Coote, Catherine Rennie, Gillian M. F. Wallace, Fatima S. Govani, Genomics England Res Consortium
JOURNAL OF MEDICAL GENETICS
(2023)
