Alternative Diagnoses in the Work Up of Down Syndrome Regression Disorder

Jonathan D Santoro; Mellad M Khoshnood; Lina Nguyen; Benjamin N Vogel; Natalie K Boyd; Kelli C Paulsen; Michael S Rafii

doi:10.1007/s10803-023-06057-9

Alternative Diagnoses in the Work Up of Down Syndrome Regression Disorder

J Autism Dev Disord. 2023 Aug 16. doi: 10.1007/s10803-023-06057-9. Online ahead of print.

Authors

Jonathan D Santoro^{1

2

3}, Mellad M Khoshnood⁴, Lina Nguyen⁴, Benjamin N Vogel⁴, Natalie K Boyd⁴, Kelli C Paulsen⁴, Michael S Rafii^{5

6}

Affiliations

¹ Division of Neuroimmunology, Children's Hospital Los Angeles, Los Angeles, CA, USA. jdsantoro@chla.usc.edu.
² Department of Neurology, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA. jdsantoro@chla.usc.edu.
³ Division of Neurology, Children's Hospital Los Angeles, 4650 Sunset Blvd, MS 82, Los Angeles, CA, 90027, USA. jdsantoro@chla.usc.edu.
⁴ Division of Neuroimmunology, Children's Hospital Los Angeles, Los Angeles, CA, USA.
⁵ Department of Neurology, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA.
⁶ Department of Neurology, Alzheimer's Therapeutic Research Institute (ATRI), Keck School of Medicine, University of Southern California, San Diego, CA, USA.

PMID: 37584771
DOI: 10.1007/s10803-023-06057-9

Abstract

Purpose: Down Syndrome Regression Disorder (DSRD) is a diagnosis of exclusion. Psychiatric and neuroimmunologic etiologies have been proposed although the exact etiology remains unknown. This study sought to review non-DSRD diagnoses at a large quaternary medical center specializing in the diagnosis of DSRD and compare clinical characteristics between those diagnosed with DSRD and those with non-DSRD diagnoses.

Methods: The authors performed a single-center retrospective, chart-based, review of referrals for developmental regression in individuals with Down syndrome.

Results: Two hundred and sixty-six individuals were evaluated for DSRD and of these, 54 (20%) ultimately had alternative diagnoses. Individuals with DSRD were more likely to have shorter nadir to clinical symptoms (p = 0.01, 95% CI: 0.36-0.47) and have preceding triggers (p < 0.001, 95% CI: 1.13-1.43) compared to those with alternative diagnoses. Individuals with non-DSRD diagnoses were more likely to be born premature (p = 0.01, 95% CI: 0.51-0.87) and have a history of epilepsy (p = 0.01, 95% CI: 0.23-0.77) but were also less likely to have a history of cytokine abnormalities on bloodwork (p < 0.001, 95% CI: 1.19-1.43) and have catatonia (p < 0.001, 95% CI: 1.54-2.17). The majority of alternative diagnoses (41/54, 76%) were autism spectrum disorder. In these cases, symptoms were more likely to be longstanding (symptoms > 12 months) and earlier onset (median 8 years, IQR: 6-11). Other diagnoses included epilepsy (5/54, 9%), Celiac disease (5/54, 9%), cerebrovascular disease (3/54, 6%).

Conclusions: This study identifies that 20% of individuals referred with concerns for DSRD have alternative diagnoses. The majority of these diagnoses were autism, but rare treatable conditions were also identified, highlighting the importance of a thorough neurodiagnostic assessment.

Keywords: Diagnosis; Down syndrome; Regression; Testing; Work up.