Causes of Down syndrome regression disorder: a scoping review

ABSTRACT 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, partic...

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Main Authors: Manuelle Maria Pereira Natividade, Adson José Moreira, Lívia Silva Nassif, Bárbara Rodrigues Alvernaz dos Santos, Marcus Carvalho Borin, Juliana Alvares-Teodoro, Francisco de Assis Acurcio, Augusto Afonso Guerra Junior
Format: Article
Language:English
Published: Associação Neurologia Cognitiva e do Comportamento 2025-07-01
Series:Dementia & Neuropsychologia
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Online Access:http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1980-57642025001000300&lng=en&tlng=en
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Summary:ABSTRACT 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.
ISSN:1980-5764