Romy van de Putte1, Iris A L M van Rooij2,3, Carlo L M Marcelis4, Michel Guo2, Han G Brunner4,5, Marie-Claude Addor6, Clara Cavero-Carbonell7, Carlos M Dias8, Elizabeth S Draper9, Larraitz Etxebarriarteun10, Miriam Gatt11, Martin Haeusler12, Babak Khoshnood13, Kari Klungsoyr14, Jenny J Kurinczuk15, Monica Lanzoni16, Anna Latos-Bielenska17, Karen Luyt18, Mary T O'Mahony19, Nicola Miller20, Carmel Mullaney21, Vera Nelen22, Amanda J Neville23, Isabelle Perthus24, Anna Pierini25, Hanitra Randrianaivo26, Judith Rankin27, Anke Rissmann28, Florence Rouget29, Bruno Schaub30, David Tucker31, Diana Wellesley32, Awi Wiesel33, Natalya Zymak-Zakutnia34, Maria Loane35, Ingeborg Barisic36, Hermien E K de Walle37, Nel Roeleveld2, Jorieke E H Bergman37. 1. Department for Health Evidence, Radboud Institute for Health Sciences, Radboud University Medical Center (Radboudumc), Nijmegen, The Netherlands. Romy.vandePutte@radboudumc.nl. 2. Department for Health Evidence, Radboud Institute for Health Sciences, Radboud University Medical Center (Radboudumc), Nijmegen, The Netherlands. 3. Paediatric Surgery, Radboudumc Amalia Children's Hospital, Nijmegen, The Netherlands. 4. Department of Human Genetics, Radboudumc, Nijmegen, The Netherlands. 5. Department of Clinical Genetics, Maastricht University Medical Centre, Maastricht, The Netherlands. 6. Department of Woman-Mother-Child, University Medical Center CHUV, Lausanne, Switzerland. 7. Rare Diseases Research Unit, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region, Valencia, Spain. 8. Epidemiology Department, National Institute of Health Doctor Ricardo Jorge, Lisbon, Portugal. 9. Department of Health Sciences, University of Leicester, Leicester, UK. 10. Department of Health, Public Health Service, Basque Government Basque Country, Vitoria-Gasteiz, Spain. 11. Malta Congenital Anomalies Register, Directorate for Health Information and Research, Pietà, Malta. 12. Department of Obstetrics and Gynecology, Medical University of Graz, Graz, Austria. 13. INSERM UMR 1153, Obstetrical, Perinatal and Pediatric Epidemiology Research Team (EPOPé), Center of Research in Epidemiology and Statistics Sorbonne Paris Cité (CRESS), DHU Risks in Pregnancy, Paris Descartes University, Paris, France. 14. Department of Global Public Health and Primary Care, Division for Mental and Physical Health, Norwegian Institute of Public Health, University of Bergen, Bergen, Norway. 15. National Perinatal Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK. 16. European Commission, Joint Research Centre (JRC), Ispra, Italy. 17. Department of Medical Genetics, Poznan University of Medical Sciences, Poznań, Poland. 18. South West Congenital Anomaly Register (SWCAR), Bristol Medical School, University of Bristol, Bristol, UK. 19. Department of Public Health, Health Service Executive - South, Cork, Ireland. 20. National Congenital Anomaly and Rare Disease Registration Service, Public Health England, Newcastle upon Tyne, UK. 21. Department of Public Health, HSE South East, Lacken, Kilkenny, Ireland. 22. Provinciaal Instituut voor Hygiene (PIH), Antwerp, Belgium. 23. Registro IMER - IMER Registry (Emila Romagna Registry of Birth Defects), Center for Clinical and Epidemiological Research, University of Ferrara, Azienda Ospedaliero-Universitaria di Ferrara, Ferrara, Italy. 24. Auvergne registry of congenital anomalies (CEMC-Auvergne), Department of clinical genetics, Centre de Référence des Maladies Rares, University Hospital of Clermont-Ferrand, Clermont-Ferrand, France. 25. Tuscany Registry of Congenital Defects (TRDC), Institute of Clinical Physiology - National Research Council/Fondazione Toscana Gabriele Monasterio, Pisa, Italy. 26. Register of Congenital Malformations of Reunion Island, CHU Réunion, St Pierre, France. 27. Institute of Health and Society, Newcastle University, Newcastle, UK. 28. Malformation Monitoring Centre Saxony-Anhalt, Medical Faculty Otto-von-Guericke University, Magdeburg, Germany. 29. Brittany Registry of Congenital Anomalies, CHU Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail), University Rennes, Rennes, France. 30. French West Indies Registry, Registre des Malformations des Antilles (REMALAN), Maison de la Femme de la Mère et de l'Enfant, University Hospital of Martinique, Fort-de-France, France. 31. CARIS, Public Health Wales, Singleton Hospital, Swansea, Wales, UK. 32. Wessex Clinical Genetics Department, Princess Anne Hospital, Southampton, UK. 33. Department of Pediatrics, Birth Registry Mainz Model, University Medical Center of Mainz, Mainz, Germany. 34. OMNI-Net Ukraine Birth Defects Program and Khmelnytsky City Children's Hospital, Khmelnytsky, Ukraine. 35. Centre for Maternal, Fetal and lnfant Research, lnstitute of Nursing and Health Research, Ulster University, Belfast, Northern lreland, UK. 36. Centre of Excellence for Reproductive and Regenerative Medicine, Children's Hospital Zagreb, Medical School University of Zagreb, Zagreb, Croatia. 37. University of Groningen, University Medical Center Groningen, Department of Genetics, EUROCAT Northern Netherlands, Groningen, The Netherlands.
Abstract
BACKGROUND: The VACTERL (Vertebral anomalies, Anal atresia, Cardiac malformations, Tracheo-Esophageal fistula, Renal anomalies, Limb abnormalities) association is the non-random occurrence of at least three of these congenital anomalies: vertebral, anal, cardiac, tracheo-esophageal, renal, and limb anomalies. Diagnosing VACTERL patients is difficult, as many disorders have multiple features in common with VACTERL. The aims of this study were to clearly outline component features, describe the phenotypic spectrum among the largest group of VACTERL patients thus far reported, and to identify phenotypically similar subtypes. METHODS: A case-only study was performed assessing data on 501 cases recorded with VACTERL in the JRC-EUROCAT (Joint Research Centre-European Surveillance of Congenital Anomalies) central database (birth years: 1980-2015). We differentiated between major and minor VACTERL features and anomalies outside the VACTERL spectrum to create a clear definition of VACTERL. RESULTS: In total, 397 cases (79%) fulfilled our VACTERL diagnostic criteria. The most commonly observed major VACTERL features were anorectal malformations and esophageal atresia/tracheo-esophageal fistula (both occurring in 62% of VACTERL cases), followed by cardiac (57%), renal (51%), vertebral (33%), and limb anomalies (25%), in every possible combination. Three VACTERL subtypes were defined: STRICT-VACTERL, VACTERL-LIKE, and VACTERL-PLUS, based on severity and presence of additional congenital anomalies. CONCLUSION: The clearly defined VACTERL component features and the VACTERL subtypes introduced will improve both clinical practice and etiologic research.
BACKGROUND: The VACTERL (Vertebral anomalies, Anal atresia, Cardiac malformations, Tracheo-Esophageal fistula, Renal anomalies, Limb abnormalities) association is the non-random occurrence of at least three of these congenital anomalies: vertebral, anal, cardiac, tracheo-esophageal, renal, and limb anomalies. Diagnosing VACTERL patients is difficult, as many disorders have multiple features in common with VACTERL. The aims of this study were to clearly outline component features, describe the phenotypic spectrum among the largest group of VACTERL patients thus far reported, and to identify phenotypically similar subtypes. METHODS: A case-only study was performed assessing data on 501 cases recorded with VACTERL in the JRC-EUROCAT (Joint Research Centre-European Surveillance of Congenital Anomalies) central database (birth years: 1980-2015). We differentiated between major and minor VACTERL features and anomalies outside the VACTERL spectrum to create a clear definition of VACTERL. RESULTS: In total, 397 cases (79%) fulfilled our VACTERL diagnostic criteria. The most commonly observed major VACTERL features were anorectal malformations and esophageal atresia/tracheo-esophageal fistula (both occurring in 62% of VACTERL cases), followed by cardiac (57%), renal (51%), vertebral (33%), and limb anomalies (25%), in every possible combination. Three VACTERL subtypes were defined: STRICT-VACTERL, VACTERL-LIKE, and VACTERL-PLUS, based on severity and presence of additional congenital anomalies. CONCLUSION: The clearly defined VACTERL component features and the VACTERL subtypes introduced will improve both clinical practice and etiologic research.
Authors: Naikhoba C O Munabi; Shady Mikhail; Omar Toubat; Michelle Webb; Allyn Auslander; Pedro A Sanchez-Lara; Zarko Manojlovic; Ryan J Schmidt; David Craig; William P Magee; Subramanyan Ram Kumar Journal: Am J Med Genet A Date: 2022-04-06 Impact factor: 2.578
Authors: Moonjung Jung; Ramanagouda Ramanagoudr-Bhojappa; Sylvie van Twest; Rasim Ozgur Rosti; Vincent Murphy; Winnie Tan; Frank X Donovan; Francis P Lach; Danielle C Kimble; Caroline S Jiang; Roger Vaughan; Parinda A Mehta; Filomena Pierri; Carlo Dufour; Arleen D Auerbach; Andrew J Deans; Agata Smogorzewska; Settara C Chandrasekharappa Journal: Blood Date: 2020-04-30 Impact factor: 25.476
Authors: Romy van de Putte; Iris A L M van Rooij; Cynthia P Haanappel; Carlo L M Marcelis; Han G Brunner; Marie-Claude Addor; Clara Cavero-Carbonell; Carlos M Dias; Elizabeth S Draper; Larraitz Etxebarriarteun; Miriam Gatt; Babak Khoshnood; Agnieszka Kinsner-Ovaskainen; Kari Klungsoyr; Jenny J Kurinczuk; Anna Latos-Bielenska; Karen Luyt; Mary T O'Mahony; Nicola Miller; Carmel Mullaney; Vera Nelen; Amanda J Neville; Isabelle Perthus; Anna Pierini; Hanitra Randrianaivo; Judith Rankin; Anke Rissmann; Florence Rouget; Bruno Schaub; David Tucker; Diana Wellesley; Awi Wiesel; Natalya Zymak-Zakutnia; Maria Loane; Ingeborg Barisic; Hermien E K de Walle; Jorieke E H Bergman; Nel Roeleveld Journal: Birth Defects Res Date: 2020-04-22 Impact factor: 2.344
Authors: Paul Costin Pariza; Irina Stavarache; Vasile Adrian Dumitru; Octaviana Munteanu; Tiberiu Augustin Georgescu; Valentin Varlas; Consuela-Mădălina Gheorghe; Roxana Elena Bohîlțea Journal: J Med Life Date: 2021 Nov-Dec
Authors: Romy van de Putte; Hermien E K de Walle; Kirsten J M van Hooijdonk; Ivo de Blaauw; Carlo L M Marcelis; Arno van Heijst; Jacques C Giltay; Kirsten Y Renkema; Paul M A Broens; Erwin Brosens; Cornelius E J Sloots; Jorieke E H Bergman; Nel Roeleveld; Iris A L M van Rooij Journal: Birth Defects Res Date: 2020-07-22 Impact factor: 2.344
Authors: Philip J Lupo; A J Agopian; Renata H Benjamin; Angela E Scheuerle; Daryl A Scott; Maria Luisa Navarro Sanchez; Peter H Langlois; Mark A Canfield; Hope Northrup; Christian P Schaaf; Joseph W Ray; Scott D McLean; Han Chen; Michael D Swartz Journal: Pediatr Res Date: 2021-06-30 Impact factor: 3.953