Biallelic MADD variants cause a phenotypic spectrum ranging from developmental delay to a multisystem disorder

Pauline E Schneeberger 1 , Fanny Kortüm 1 , Georg Christoph Korenke 2 , Malik Alawi 3 , René Santer 4 , Mathias Woidy 4 , Daniela Buhas 5 6 , Stephanie Fox 5 6 , Jane Juusola 7 , Majid Alfadhel 8 9 10 , Bryn D Webb 11 12 13 , Emanuele G Coci 14 15 , Rami Abou Jamra 16 , Manuela Siekmeyer 17 , Saskia Biskup 18 , Corina Heller 18 , Esther M Maier 19 , Poupak Javaher-Haghighi 20 , Maria F Bedeschi 21 , Paola F Ajmone 22 , Maria Iascone 23 , Hilde Peeters 24 , Katleen Ballon 25 , Jaak Jaeken 26 , Aroa Rodríguez Alonso 27 , María Palomares-Bralo 28 , Fernando Santos-Simarro 28 , Marije E C Meuwissen 29 , Diane Beysen 30 , R Frank Kooy 31 , Henry Houlden 32 , David Murphy 32 , Mohammad Doosti 33 , Ehsan G Karimiani 33 34 , Majid Mojarrad 35 36 37 , Reza Maroofian 32 , Lenka Noskova 38 , Stanislav Kmoch 38 , Tomas Honzik 39 , Heidi Cope 40 , Amarilis Sanchez-Valle 41 , Undiagnosed Diseases Network; Bruce D Gelb 11 12 13 , Ingo Kurth 42 43 , Maja Hempel 1 , Kerstin Kutsche 1

  1. Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
  2. Klinik für Neuropädiatrie und angeborene Stoffwechselerkrankungen, Klinikum Oldenburg, Oldenburg, Germany.
  3. Bioinformatics Core Unit, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
  4. Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
  5. Division of Medical Genetics, Department of Specialized Medicine, McGill University Health Centre, Montreal, Canada.
  6. Human Genetics Department, McGill University, Montreal, Canada.
  7. GeneDx, Gaithersburg, USA.
  8. Division of Genetics, Department of Pediatrics, King Abdullah specialized Children’s Hospital, King Abdulaziz Medical City, Ministry of National Guard-Health Affairs (MNGHA), Riyadh, Saudi Arabia.
  9. Medical Genomics Research Department, King Abdullah International Medical Research Center (KAIMRC), Ministry of National Guard-Health Affairs (MNGHA), Riyadh, Saudi Arabia.
  10. King Saud Bin Abdulaziz University for Health Sciences, Ministry of National Guard-Health Affairs (MNGHA), Riyadh, Saudi Arabia.
  11. Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, USA.
  12. Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, USA.
  13. Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, USA.
  14. Department for Neuropediatrics, University Children’s Hospital, Ruhr University Bochum, Bochum, Germany.
  15. Department of Pediatrics, Prignitz Hospital, Brandenburg Medical School, Germany.
  16. Institute of Human Genetics, University Medical Center Leipzig, Leipzig, Germany.
  17. Universitätsklinikum Leipzig – AöR, University of Leipzig, Hospital for Children and Adolescents, Leipzig, Germany.
  18. CeGaT GmbH and Praxis für Humangenetik Tübingen, Tübingen, Germany.
  19. Dr. von Hauner Children’s Hospital, University of Munich, Munich, Germany.
  20. Medicover Humangenetik Hannover, Hanover, Germany.
  21. Medical Genetic Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy.
  22. Child and Adolescent Neuropsychiatric Unit, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy.
  23. Laboratorio di Genetica Medica, ASST Papa Giovanni XXIII, Bergamo, Italy.
  24. Center for Human Genetics, KU Leuven, Leuven, Belgium.
  25. Centre for Developmental Disabilities, Department of Development and Regeneration, KU Leuven, Leuven, Belgium.
  26. Center for Metabolic Diseases, KU Leuven, Leuven, Belgium.
  27. Unidad de Patología Compleja, Servicio de Pediatría, Hospital Universitario La Paz, Madrid, Spain.
  28. Instituto de Genética Médica y Molecular (INGEMM), Hospital Universitario La Paz, IdiPAZ, CIBERER, ISCIII, Madrid, Spain.
  29. Center of Medical Genetics, University Hospital Antwerp, Antwerp, Belgium.
  30. Department of Pediatric Neurology, University Hospital Antwerp, Antwerp, Belgium.
  31. Department of Medical Genetics, University of Antwerp, Antwerp, Belgium.
  32. Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology and The National Hospital for Neurology and Neurosurgery, London, UK.
  33. Next Generation Genetic Polyclinic, Mashhad, Iran.
  34. Genetics Research Centre, Molecular and Clinical Sciences Institute, St. George’s, University, London, UK.
  35. Department of Medical Genetics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
  36. Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
  37. Genetic Center of Khorasan Razavi, Mashhad, Iran.
  38. Research Unit for Rare Diseases, Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University, Prague, Czech Republic.
  39. Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic.
  40. Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, North Carolina, USA.
  41. Division of Genetics and Metabolism, College of Medicine, University of South Florida, Tampa, Florida, USA.
  42. Institute of Human Genetics, Medical Faculty, RWTH Aachen University, Aachen, Germany.
  43. Institute of Human Genetics, Jena University Hospital, Jena, Germany.