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. 2022 Jul 15:13:940175.
doi: 10.3389/fneur.2022.940175. eCollection 2022.

Assessment and Diagnosis of Down Syndrome Regression Disorder: International Expert Consensus

Jonathan D Santoro  1   2 , Lina Patel  3 , Ryan Kammeyer  4 , Robyn A Filipink  5 , Grace Y Gombolay  6 , Kathleen M Cardinale  7 , Diego Real de Asua  8 , Shahid Zaman  9 , Stephanie L Santoro  10 , Sammer M Marzouk  10 , Mellad Khoshnood  1 , Benjamin N Vogel  2 , Runi Tanna  2 , Dania Pagarkar  2 , Sofia Dhanani  2 , Maria Del Carmen Ortega  11 , Rebecca Partridge  12 , Maria A Stanley  13 , Jessica S Sanders  14 , Alison Christy  15 , Elise M Sannar  3   16 , Ruth Brown  17 , Andrew A McCormick  5 , Heather Van Mater  18 , Cathy Franklin  19 , Gordon Worley  20 , Eileen A Quinn  21 , George T Capone  22   23 , Brian Chicoine  24 , Brian G Skotko  10   25 , Michael S Rafii  2   26
Affiliations

Assessment and Diagnosis of Down Syndrome Regression Disorder: International Expert Consensus

Jonathan D Santoro et al. Front Neurol. .

Abstract

Objective: To develop standardization for nomenclature, diagnostic work up and diagnostic criteria for cases of neurocognitive regression in Down syndrome.

Background: There are no consensus criteria for the evaluation or diagnosis of neurocognitive regression in persons with Down syndrome. As such, previously published data on this condition is relegated to smaller case series with heterogenous data sets. Lack of standardized assessment tools has slowed research in this clinical area.

Methods: The authors performed a two-round traditional Delphi method survey of an international group of clinicians with experience in treating Down syndrome to develop a standardized approach to clinical care and research in this area. Thirty-eight potential panelists who had either previously published on neurocognitive regression in Down syndrome or were involved in national or international working groups on this condition were invited to participate. In total, 27 panelists (71%) represented nine medical specialties and six different countries reached agreement on preliminary standards in this disease area. Moderators developed a proposed nomenclature, diagnostic work up and diagnostic criteria based on previously published reports of regression in persons with Down syndrome.

Results: During the first round of survey, agreement on nomenclature for the condition was reached with 78% of panelists agreeing to use the term Down Syndrome Regression Disorder (DSRD). Agreement on diagnostic work up and diagnostic criteria was not reach on the first round due to low agreement amongst panelists with regards to the need for neurodiagnostic testing. Following incorporation of panelist feedback, diagnostic criteria were agreed upon (96% agreement on neuroimaging, 100% agreement on bloodwork, 88% agreement on lumbar puncture, 100% agreement on urine studies, and 96% agreement on "other" studies) as were diagnostic criteria (96% agreement).

Conclusions: The authors present international consensus agreement on the nomenclature, diagnostic work up, and diagnostic criteria for DSRD, providing an initial practical framework that can advance both research and clinical practices for this condition.

Keywords: Down syndrome; consensus; criteria & indicators; encephalopathy; regression.

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Conflict of interest statement

JDS receives research support from the National Institutes of Health, the Race to Erase MS Foundation, and the Thrasher Society. He also serves as a consultant to UCB on myelin oligodendrocyte glycoprotein antibody spectrum disorders. GG receives part-time salary support from the Centers for Disease Control and Prevention for acute flaccid myelitis disease surveillance. DA is supported by the Fondo de Investigaciones Sanitarias (FIS grant PI19/00634, from the Ministerio de Economía y Competitividad (Instituto de Salud Carlos III) and co-funded by The European Regional Development Fund (ERDF) “A way to make Europe” and the. Fondation Jérôme Lejeune (grant no. 2021a-2069). The Adult Down Syndrome Outpatient unit at Hospital Universitario de La Princesa is grateful to Licenciado don Jesús Coronado Hinojosa for his financial support of the research endeavors of our unit. BS 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. BS 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 2 years, he has received research funding from F. Hoffmann-La Roche, Inc., and LuMind Research Down Syndrome Foundation to conduct clinical trials for people with Down syndrome. BS 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 and the Professional Advisory Committee for the National Center for Prenatal and Postnatal Down Syndrome Resources. BS has a sister with Down syndrome. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Flow diagram for panelist selection and Delphi method assessment.
See this image and copyright information in PMC

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