Stephanie L Santoro1,2, Sheila Cannon3, George Capone4, Cathy Franklin5, Sarah J Hart6, Victoria Hobensack7, Priya S Kishnani6, Eric A Macklin8, Kandamurugu Manickam7, Andrew McCormick3, Patricia Nash7, Nicolas M Oreskovic9,10, Vasiliki Patsiogiannis9, Katherine Steingass7, Amy Torres9, Diletta Valentini11, Kishore Vellody3, Brian G Skotko9,10. 1. Division of Medical Genetics, Department of Pediatrics, Massachusetts General Hospital, Boston, MA, USA. ssantoro3@mgh.harvard.edu. 2. Department of Pediatrics, Harvard Medical School, Boston, MA, USA. ssantoro3@mgh.harvard.edu. 3. Down Syndrome Center of Western Pennsylvania, UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, USA. 4. Kennedy Krieger Institute, Baltimore, MD, USA. 5. Mater Research Institute, University of Queensland, South Brisbane, QLD, Australia. 6. Department of Pediatrics, Duke University Medical Center, Durham, NC, USA. 7. Department of Pediatrics, Nationwide Children's Hospital, Columbus, OH, USA. 8. Biostatistics Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. 9. Division of Medical Genetics, Department of Pediatrics, Massachusetts General Hospital, Boston, MA, USA. 10. Department of Pediatrics, Harvard Medical School, Boston, MA, USA. 11. Pediatric and Infectious Disease Unit, Bambino Gesù Children's Hospital, Rome, Italy.
Abstract
PURPOSE: An entity of regression in Down syndrome (DS) exists that affects adolescents and young adults and differs from autism spectrum disorder and Alzheimer disease. METHODS: Since 2017, an international consortium of DS clinics assembled a database of patients with unexplained regression and age- and sex-matched controls. Standardized data on clinical symptoms and tiered medical evaluations were collected. Elements of the proposed definition of unexplained regression in DS were analyzed by paired comparisons between regression cases and matched controls. RESULTS: We identified 35 patients with DS and unexplained regression, with a mean age at regression of 17.5 years. Diagnostic features differed substantially between regression cases and matched controls (p < 0.001 for all but externalizing behaviors). Patients with regression had four times as many mental health concerns (p < 0.001), six times as many stressors (p < 0.001), and seven times as many depressive symptoms (p < 0.001). Tiered medical evaluation most often identified abnormalities in vitamin D 25-OH levels, polysomnograms, thyroid peroxidase antibodies, and celiac screens. Analysis of the subset of patients with nondiagnostic medical evaluations reinforced the proposed definition. CONCLUSIONS: Our case-control evidence supports a proposed definition of unexplained regression in Down syndrome. Establishing this clinical definition supports future research and investigation of an underlying mechanism.
PURPOSE: An entity of regression in Down syndrome (DS) exists that affects adolescents and young adults and differs from autism spectrum disorder and Alzheimer disease. METHODS: Since 2017, an international consortium of DS clinics assembled a database of patients with unexplained regression and age- and sex-matched controls. Standardized data on clinical symptoms and tiered medical evaluations were collected. Elements of the proposed definition of unexplained regression in DS were analyzed by paired comparisons between regression cases and matched controls. RESULTS: We identified 35 patients with DS and unexplained regression, with a mean age at regression of 17.5 years. Diagnostic features differed substantially between regression cases and matched controls (p < 0.001 for all but externalizing behaviors). Patients with regression had four times as many mental health concerns (p < 0.001), six times as many stressors (p < 0.001), and seven times as many depressive symptoms (p < 0.001). Tiered medical evaluation most often identified abnormalities in vitamin D 25-OH levels, polysomnograms, thyroid peroxidase antibodies, and celiac screens. Analysis of the subset of patients with nondiagnostic medical evaluations reinforced the proposed definition. CONCLUSIONS: Our case-control evidence supports a proposed definition of unexplained regression in Down syndrome. Establishing this clinical definition supports future research and investigation of an underlying mechanism.
Entities:
Keywords:
Down syndrome; Down syndrome disintegrative disorder; regression; trisomy 21
Authors: Jonathan D Santoro; Rebecca Partridge; Runi Tanna; Dania Pagarkar; Mellad Khoshnood; Mustafa Rehmani; Ryan M Kammeyer; Grace Y Gombolay; Kristen Fisher; Allison Conravey; Jane El-Dahr; Alison L Christy; Lina Patel; Melanie A Manning; Heather Van Mater; Michael S Rafii; Eileen A Quinn Journal: J Neurodev Disord Date: 2022-06-03 Impact factor: 4.074
Authors: Jonathan D Santoro; Lina Patel; Ryan Kammeyer; Robyn A Filipink; Grace Y Gombolay; Kathleen M Cardinale; Diego Real de Asua; Shahid Zaman; Stephanie L Santoro; Sammer M Marzouk; Mellad Khoshnood; Benjamin N Vogel; Runi Tanna; Dania Pagarkar; Sofia Dhanani; Maria Del Carmen Ortega; Rebecca Partridge; Maria A Stanley; Jessica S Sanders; Alison Christy; Elise M Sannar; Ruth Brown; Andrew A McCormick; Heather Van Mater; Cathy Franklin; Gordon Worley; Eileen A Quinn; George T Capone; Brian Chicoine; Brian G Skotko; Michael S Rafii Journal: Front Neurol Date: 2022-07-15 Impact factor: 4.086