Abstract in English, Portuguese
Down syndrome regression disorder (DSRD) is characterized by an acute or subacute neurocognitive regression that severely impacts the autonomy and quality of life of individuals with Down syndrome (DS). Despite its growing recognition, understanding of the condition remains limited, particularly regarding its etiology and the factors contributing to its development.
Objective: The aim of this study was to systematically map the available evidence regarding the potential causes of DSRD and the factors that may contribute to its development.
Methods: Following the Joanna Briggs Institute (JBI) methodology for scoping reviews, a comprehensive three-step search strategy was conducted across MEDLINE (PubMed), Embase, Cochrane, and Lilacs. Studies published in any language were considered, with no restrictions on publication date.
Results: In total, 14 studies met the eligibility criteria. The findings consistently point to chronic autoimmunity and immune dysregulation as potential causes of DSRD. Additionally, the contribution of genetic variants associated with the type 1 interferon inflammatory response has been suggested. Finally, the role of psychosocial and environmental stressors was highlighted, as these are considered potential triggers that precede the onset of DSRD manifestations.
Conclusion: The hypothesis that DSRD is a multifactorial condition seems reasonable. Nevertheless, the immune system may play a central role in its development, as the identified causes converge toward a neuroinflammatory process. Furthermore, the contribution of genetic variants associated with the inflammatory response and the role of psychosocial stressors as triggers for DSRD also appear plausible.
Seenivasan A, Rachamim E, Santoro JD. A Cross-Sectional Study Survey to Develop a Clinical Screen for Down Syndrome Regression Disorder in the United Kingdom. Am J Med Genet A. 2025 Aug 5:e64207. doi: 10.1002/ajmg.a.64207. Epub ahead of print. PMID: 40762403.
Abstract
Down syndrome regression disorder (DSRD) is marked by a sudden loss of previously acquired skills or behavior without a clear cause in individuals with Down syndrome (DS). Awareness of this condition has increased recently, with new therapeutic options under trial. The precise incidence is unknown due to confounding factors and gaps in capturing symptoms within the broader community. The application of narrower guidelines presents challenges in accurately reporting symptoms across the wider DS community. We conducted a survey across the UK based on 2022 DSRD consensus guidelines among parents and carers of children and young adults with DS, with 158 detailed responses about demographics, symptoms, and triggers. The survey revealed critical insights into the challenges faced by parents and carers. Results indicate a significant diagnostic threshold for DSRD within a symptom score range of 20.2-25.6, capturing about 80% of cases. Patients scoring above 20.2 are at high risk for DSRD from a statistical perspective. This threshold is vital for early detection and intervention, potentially improving patient outcomes. While it may overestimate diagnoses, the questionnaire serves as a screening tool for identifying those at risk.
Silverman M, Rezvan PH, Vogel BN, Yousuf MM, Lucas MC, Kazerooni L, Jafarpour S, Santoro JD. Cerebral Blood Flow Abnormalities in Down Syndrome Regression Disorder. Pediatr Neurol. 2025 Jul 18;171:34-40. doi: 10.1016/j.pediatrneurol.2025.07.007. Epub ahead of print. PMID: 40763623; PMCID: PMC12326077.
Abstract
Background: This study aimed to examine cerebral blood flow velocity (CBFV) in the middle cerebral artery (MCA) and internal carotid artery (ICA) of individuals with Down syndrome (DS) and Down Syndrome Regression Disorder (DSRD).
Methods: A single-center, prospective observational study was performed to evaluate CBFV in individuals with DS and DSRD using transcranial Doppler (TCD) ultrasound. Individuals with DS without regression and DSRD were recruited in a 1:1 manner. TCD studies were performed using a standardized protocol for children.
Results: In total, 104 individuals were enrolled, with 60 (57.7%) having DSRD and 44 (42.3%) having DS only. Individuals with DSRD had lower average MCA values (mean difference: -6.89, 95% confidence interval [CI]: -12.88, -0.90; P = 0.024) and ICA values (-4.98, 95% CI: -9.58, -0.38; P = 0.034) when compared with individuals with DS only. These differences were more apparent in the left MCA (-8.97, 95% CI: -15.89, -2.06; P = 0.011) and left ICA (-5.65, 95% CI: -11.11, -0.19; P = 0.042). Age, hemodynamic measures, and neuropsychiatric disease severity did not modify the differences in MCA and ICA between patients with DSRD and DS. However, in patients with DSRD, MCA values decreased on average by -0.40 (95% CI: -0.78, -0.02; P = 0.038) for every unit increase in heart rate compared with patients with DS.
Conclusions: This study revealed CBFV alterations in individuals with DSRD when compared with DS alone, demonstrating reduced CBFV in both the MCA and ICA. These findings suggest disrupted cerebral autoregulation, potentially driven by the presence of catatonia in individuals with DSRD.
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