TY - JOUR
T1 - Unexplained regression in Down syndrome
T2 - 35 cases from an international Down syndrome database
AU - Santoro, Stephanie L.
AU - Cannon, Sheila
AU - Capone, George
AU - Franklin, Cathy
AU - Hart, Sarah J.
AU - Hobensack, Victoria
AU - Kishnani, Priya S.
AU - Macklin, Eric A.
AU - Manickam, Kandamurugu
AU - McCormick, Andrew
AU - Nash, Patricia
AU - Oreskovic, Nicolas M.
AU - Patsiogiannis, Vasiliki
AU - Steingass, Katherine
AU - Torres, Amy
AU - Valentini, Diletta
AU - Vellody, Kishore
AU - Skotko, Brian G.
N1 - Funding Information:
B.G.S. occasionally consults on the topic of Down syndrome through Gerson Lehrman Group. He receives remuneration from Down syndrome nonprofit organizations for speaking engagements and associated travel expenses. He receives annual royalties from Woodbine House, Inc., for the publication of his book Fasten Your Seatbelt: A Crash Course on Down Syndrome for Brothers and Sisters. Within the past two years, he has received research funding from F. Hoffmann-La Roche, Inc. and LuMind IDSC Research Down Syndrome Foundation to conduct clinical trials for people with Down syndrome. He is occasionally asked to serve as an expert witness for legal cases where Down syndrome is discussed. He serves in a nonpaid capacity on the Honorary Board of Directors for the Massachusetts Down Syndrome Congress, the Board of Directors for the Band of Angels Foundation, and the Professional Advisory Committee for the National Center for Prenatal and Postnatal Down Syndrome Resources. He has a sister with Down syndrome. S.L.S. receives research funding from the LuMind IDSC Research Down Syndrome Foundation to conduct clinical trials for people with Down syndrome. She also serves on the Professional Advisory Board for the Massachusetts Down Syndrome Congress. C.F. receives research funding from Brain Injured Children’s Aftercare Recovery Endeavours (BICARE). She has a young nephew with Down syndrome. The other authors declare no conflicts of interest.
Funding Information:
The 28-item proposed definition of URDS is supported by case–control evidence, providing a foundation for future research and investigation of underlying mechanisms.
Publisher Copyright:
© 2019, American College of Medical Genetics and Genomics.
PY - 2020/4/1
Y1 - 2020/4/1
N2 - 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.
AB - 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.
KW - Down syndrome
KW - Down syndrome disintegrative disorder
KW - regression
KW - trisomy 21
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U2 - 10.1038/s41436-019-0706-8
DO - 10.1038/s41436-019-0706-8
M3 - Article
C2 - 31767984
AN - SCOPUS:85075455535
SN - 1098-3600
VL - 22
SP - 767
EP - 776
JO - Genetics in Medicine
JF - Genetics in Medicine
IS - 4
ER -