. 2024 Apr;194(4):e63477.

doi: 10.1002/ajmg.a.63477. Epub 2023 Nov 15.

The 8th International RASopathies Symposium: Expanding research and care practice through global collaboration and advocacy

Elizabeth I Pierpont¹, Anton M Bennett², Lisa Schoyer³, Beth Stronach³, April Anschutz³, Sarah C Borrie⁴, Benjamin Briggs⁵, Emma Burkitt-Wright⁶, Pau Castel⁷, Ion C Cirstea^{8

9}, Fieke Draaisma¹⁰, Michelle Ellis³, Vanessa S Fear¹¹, Megan N Frone¹², Elisabetta Flex¹³, Bruce D Gelb¹⁴, Tamar Green¹⁵, Karen W Gripp¹⁶, Sattar Khoshkhoo¹⁷, Mark W Kieran¹⁸, Karolin Kleemann^{19

20}, Bonita P Klein-Tasman²¹, Maria I Kontaridis^{22

23

24}, Paul Kruszka²⁵, Chiara Leoni²⁶, Clifford Z Liu¹⁴, Nadia Merchant²⁷, Pilar L Magoulas²⁸, Christopher Moertel¹, Carlos E Prada^{29

30}, Katherine A Rauen³¹, Renée Roelofs³², Rodrigue Rossignol³³, Christine Sevilla³⁴, Gigi Sevilla³⁵, Ryan Sheedy³⁶, Elliot Stieglitz³⁷, Daochun Sun³⁸, Dagmar Tiemens¹⁰, Forest White³⁹, Ellen Wingbermühle³², Cordula Wolf⁴⁰, Martin Zenker⁴¹, Gregor Andelfinger⁴²

Affiliations

¹ Department of Pediatrics, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
² Department of Pharmacology, Yale School of Medicine, New Haven, Connecticut, USA.
³ RASopathies Network, Los Angeles, California, USA.
⁴ KU Leuven, Laboratory for the Research of Neurodegenerative Diseases, Leuven, Belgium.
⁵ School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.
⁶ Manchester Centre for Genomic Medicine, Manchester University NHS Foundation Trust and University of Manchester, Manchester, UK.
⁷ Department of Biochemistry & Molecular Pharmacology, NYU Grossman School of Medicine, New York, New York, USA.
⁸ Institute of Comparative Molecular Endocrinology, Ulm University, Ulm, Germany.
⁹ Institute of Applied Physiology, Ulm University, Ulm, Germany.
¹⁰ Department of Pediatrics, Radboud Institute for Health Sciences, Radboud University Medical Center, Amalia Children's Hospital, Nijmegen, The Netherlands.
¹¹ Translational Genetics, Precision Health, Telethon Kids Institute, The University of Western Australia, Perth, Western Australia, Australia.
¹² Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland, USA.
¹³ Department of Oncology and Molecular Medicine, Instituo Superiore di Sanità, Rome, Italy.
¹⁴ Mindich Child Health and Development Institute and the Departments of Pediatrics and Genetics and Genomic Sciences, Icahn School of Medicine, New York, New York, USA.
¹⁵ Division of Interdisciplinary Brain Sciences, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California, USA.
¹⁶ Division of Medical Genetics, Department of Pediatrics, Nemours Children's Hospital, Orlando, Florida, USA.
¹⁷ Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
¹⁸ Research and Development, Day One Biopharmaceuticals, Brisbane, California, USA.
¹⁹ Clinic for Cardiothoracic and Vascular Surgery, University Medical Center Göttingen, Göttingen, Germany.
²⁰ German Center for Cardiovascular Research (DZHK), Partner Site Göttingen, Göttingen, Germany.
²¹ Department of Psychology, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin, USA.
²² Department of Biomedical Research and Translational Medicine, Masonic Medical Research Institute, Utica, New York, USA.
²³ Division of Cardiology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
²⁴ Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, USA.
²⁵ GeneDx, Gaithersburg, Maryland, USA.
²⁶ Center for Rare Diseases and Birth Defects, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A.Gemelli, IRCCS, Rome, Italy.
²⁷ Division of Endocrinology, Children's National Hospital, Washington, DC, USA.
²⁸ Department of Molecular and Human Genetics, Baylor College of Medicine and Texas Children's Hospital, Houston, Texas, USA.
²⁹ Division of Genetics, Genomics, and Metabolism, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, USA.
³⁰ Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
³¹ Department of Pediatrics, Division of Genomic Medicine, University of California, Davis, Davis, California, USA.
³² Centre of Excellence for Neuropsychiatry, Vincent van Gogh Institute for Psychiatry, Venray, The Netherlands.
³³ Rare Diseases, Genetics and Metabolism, University of Bordeaux, Bordeaux, France.
³⁴ Parent Advocate, CFC Syndrome, Lombard, Illinois, USA.
³⁵ Self Advocate, CFC Syndrome, Lombard, Illinois, USA.
³⁶ Parent Advocate, Costello Syndrome, Centerton, Arkansas, USA.
³⁷ Department of Pediatrics, Benioff Children's Hospital, University of California, Oakland, California, USA.
³⁸ Cancer Biology & Genetics Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
³⁹ Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
⁴⁰ Department of Pediatric Cardiology and Congenital Heart Disease, German Heart Center Munich, Technical University Munich, Munich, Germany.
⁴¹ Institute of Human Genetics, University Hospital Magdeburg, Magdeburg, Germany.
⁴² Department of Anatomy and Cell Biology, McGill School of Biomedical Sciences, Montreal, Quebec, Canada.

PMID: 37969032
PMCID: PMC10939912 (available on 2025-04-01)
DOI: 10.1002/ajmg.a.63477

The 8th International RASopathies Symposium: Expanding research and care practice through global collaboration and advocacy

Elizabeth I Pierpont et al. Am J Med Genet A. 2024 Apr.

. 2024 Apr;194(4):e63477.

doi: 10.1002/ajmg.a.63477. Epub 2023 Nov 15.

Authors

Affiliations

¹ Department of Pediatrics, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
² Department of Pharmacology, Yale School of Medicine, New Haven, Connecticut, USA.
³ RASopathies Network, Los Angeles, California, USA.
⁴ KU Leuven, Laboratory for the Research of Neurodegenerative Diseases, Leuven, Belgium.
⁵ School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.
⁶ Manchester Centre for Genomic Medicine, Manchester University NHS Foundation Trust and University of Manchester, Manchester, UK.
⁷ Department of Biochemistry & Molecular Pharmacology, NYU Grossman School of Medicine, New York, New York, USA.
⁸ Institute of Comparative Molecular Endocrinology, Ulm University, Ulm, Germany.
⁹ Institute of Applied Physiology, Ulm University, Ulm, Germany.
¹⁰ Department of Pediatrics, Radboud Institute for Health Sciences, Radboud University Medical Center, Amalia Children's Hospital, Nijmegen, The Netherlands.
¹¹ Translational Genetics, Precision Health, Telethon Kids Institute, The University of Western Australia, Perth, Western Australia, Australia.
¹² Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland, USA.
¹³ Department of Oncology and Molecular Medicine, Instituo Superiore di Sanità, Rome, Italy.
¹⁴ Mindich Child Health and Development Institute and the Departments of Pediatrics and Genetics and Genomic Sciences, Icahn School of Medicine, New York, New York, USA.
¹⁵ Division of Interdisciplinary Brain Sciences, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California, USA.
¹⁶ Division of Medical Genetics, Department of Pediatrics, Nemours Children's Hospital, Orlando, Florida, USA.
¹⁷ Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
¹⁸ Research and Development, Day One Biopharmaceuticals, Brisbane, California, USA.
¹⁹ Clinic for Cardiothoracic and Vascular Surgery, University Medical Center Göttingen, Göttingen, Germany.
²⁰ German Center for Cardiovascular Research (DZHK), Partner Site Göttingen, Göttingen, Germany.
²¹ Department of Psychology, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin, USA.
²² Department of Biomedical Research and Translational Medicine, Masonic Medical Research Institute, Utica, New York, USA.
²³ Division of Cardiology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
²⁴ Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, USA.
²⁵ GeneDx, Gaithersburg, Maryland, USA.
²⁶ Center for Rare Diseases and Birth Defects, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A.Gemelli, IRCCS, Rome, Italy.
²⁷ Division of Endocrinology, Children's National Hospital, Washington, DC, USA.
²⁸ Department of Molecular and Human Genetics, Baylor College of Medicine and Texas Children's Hospital, Houston, Texas, USA.
²⁹ Division of Genetics, Genomics, and Metabolism, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, USA.
³⁰ Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
³¹ Department of Pediatrics, Division of Genomic Medicine, University of California, Davis, Davis, California, USA.
³² Centre of Excellence for Neuropsychiatry, Vincent van Gogh Institute for Psychiatry, Venray, The Netherlands.
³³ Rare Diseases, Genetics and Metabolism, University of Bordeaux, Bordeaux, France.
³⁴ Parent Advocate, CFC Syndrome, Lombard, Illinois, USA.
³⁵ Self Advocate, CFC Syndrome, Lombard, Illinois, USA.
³⁶ Parent Advocate, Costello Syndrome, Centerton, Arkansas, USA.
³⁷ Department of Pediatrics, Benioff Children's Hospital, University of California, Oakland, California, USA.
³⁸ Cancer Biology & Genetics Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
³⁹ Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
⁴⁰ Department of Pediatric Cardiology and Congenital Heart Disease, German Heart Center Munich, Technical University Munich, Munich, Germany.
⁴¹ Institute of Human Genetics, University Hospital Magdeburg, Magdeburg, Germany.
⁴² Department of Anatomy and Cell Biology, McGill School of Biomedical Sciences, Montreal, Quebec, Canada.

PMID: 37969032
PMCID: PMC10939912 (available on 2025-04-01)
DOI: 10.1002/ajmg.a.63477

Abstract

Germline pathogenic variants in the RAS/mitogen-activated protein kinase (MAPK) signaling pathway are the molecular cause of RASopathies, a group of clinically overlapping genetic syndromes. RASopathies constitute a wide clinical spectrum characterized by distinct facial features, short stature, predisposition to cancer, and variable anomalies in nearly all the major body systems. With increasing global recognition of these conditions, the 8th International RASopathies Symposium spotlighted global perspectives on clinical care and research, including strategies for building international collaborations and developing diverse patient cohorts in anticipation of interventional trials. This biannual meeting, organized by RASopathies Network, was held in a hybrid virtual/in-person format. The agenda featured emerging discoveries and case findings as well as progress in preclinical and therapeutic pipelines. Stakeholders including basic scientists, clinician-scientists, practitioners, industry representatives, patients, and family advocates gathered to discuss cutting edge science, recognize current gaps in knowledge, and hear from people with RASopathies about the experience of daily living. Presentations by RASopathy self-advocates and early-stage investigators were featured throughout the program to encourage a sustainable, diverse, long-term research and advocacy partnership focused on improving health and bringing treatments to people with RASopathies.

Keywords: Costello syndrome; Noonan syndrome; cardio-facio-cutaneus syndrome; neurofibromatosis; signaling; therapeutics.

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Conflict of interest statement

Conflict of Interest Disclosure

EB-W is PI on a Novartis-funded trial and has received consultancy fees from the PIK3CA-related overgrowth spectrum advisory board and Alexion pharmaceuticals. BDG receives royalties from GeneDx, LabCorp, Prevention Genetics and Corrigan; has sponsored research agreements from OncoNova and Day One Pharmaceuticals; and has consulting agreements with BioMarin and Day One Pharmaceuticals. MIK received grant funding from Onconova Therapeutics. NM has served as an advisor for BioMarin and Pfizer. CW served as a consultant to Biomarin and Day One Therapeutics. MZ received consulting fees from Day One Pharmaceuticals. GA served as a consultant for BioMarin Pharmaceuticals and Day One Pharmaceuticals.

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The 8th International RASopathies Symposium: Expanding research and care practice through global collaboration and advocacy

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The 8th International RASopathies Symposium: Expanding research and care practice through global collaboration and advocacy

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