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

Abstract

ObjectiveTo develop standardization for nomenclature, diagnostic work up and diagnostic criteria for cases of neurocognitive regression in Down syndrome.BackgroundThere 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.MethodsThe 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.ResultsDuring 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).ConclusionsThe 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.

Immunotherapy Responsiveness and Risk of Relapse in Down Syndrome Regression Disorder

“…Ultimately, the 53% of individuals that did relapse upon wean of IVIg may represent a cohort of individuals where the etiology of their DSRD-related symptoms is potentially in ammatory in nature. Etiologies to DSRD remain poorly elucidated although emerging evidence for a neuroin ammatory component to the disease in a minority of individuals has gained traction 3,9 . Thus, the data presented in this report not only serves to highlight the therapeutic effect of IVIg in DSRD, but also provides proof of concept that the immunomodulatory effects of this therapeutic may be treating a potential, albeit unknown, in ammatory target.…”

“…All individuals evaluated in the DS neurology clinic at multiple institutions were evaluated for participation in this study. Inclusion criteria included age between 8 and 26 years at the time of symptom onset, diagnosis of either possible or probable DSRD per expert consensus guidelines 3 , and completion of clinical neurodiagnostic studies (EEG, MRI, and Lumbar Puncture (LP)). Con rmation of diagnosis was performed by an arbiter with no knowledge of the case (MK).…”

“…), IVIg therapy was then discontinued; if there was recurrence of symptoms, the patient was placed back on an every four week infusion schedule. A relapse was de ned as any sustained worsening (≥ 3 days) in any of the symptoms listed on the international DSRD criteria checklist and was determined by the evaluating clinician 3 .…”

“…Neurologic and psychiatric diseases in this population are well described, although the last decade has seen an increasing frequency of reports of the onset of subacute developmental regression of unclear etiology in individuals considered too young to develop Alzheimer's disease and too old to develop autism spectrum disorder. This condition has been referred to as Down Syndrome Regression Disorder (DSRD) and has primarily been reported in young persons with DS between ages 10 and 30 years 2,3 . Symptoms include a subacute loss of previously acquired developmental skills in the areas of language, communication, cognition, executive function, behavioral, and adaptive skills 2,4−7 .…”

Down syndrome regression disorder: updates and therapeutic advances

“…In 2022, an international multidisciplinary panel of experts in DSRD was convened and charged with the development of diagnostic recommendations [4 ▪▪ ]. The subsequent recommendations (Tables 1 and 2) were generated from a combination of existing, published evidence [8 ▪▪ ,9 ▪▪ ,11] and the desire to exclude common medical causes of encephalopathy, catatonia, and neuropsychiatric disease [4 ▪▪ ]. The work up entails a combination of blood work, EEG, neuroimaging and lumbar puncture, which can be performed in the outpatient setting.…”