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Advanced Neurology

REVIEW ARTICLE
A holistic strategy for improving cognitive

development in children with Down syndrome

Jean Adolphe Rondal*
Department of Cognitive Sciences, Cognitive Neuroscience, Faculty of Psychology, University of
Liège, Belgium

Abstract

Down syndrome (DS) is the most frequent autosomal aneuploidy. It is caused by the
triplication of human chromosome 21. Disruption of the phenotype is the result of
complex gene dosage imbalances regarding chromosome 21 and possibly other
chromosomes. The typical DS phenotype is characterized by neurodevelopmental
anomalies among which cognitive impairment is prevalent. In recent years,
experimental attempts have been made to silence one supernumerary chromosome
21 and correct gene over expressions. They are promising but not practical in
human beings. Cognitive pharmacotherapy targeting neurogenesis and synaptic
connectivity is in its early stages. In spite of these advances, a complete cure of the
condition is not reachable at the present stage and may never be possible given
the short time available between syngamy and totipotent or multipotent stem cells
in embryonic development. This means that one cannot dispense with behavioral
interventions to normalize cognitive functioning in people with DS. The paper
reviews current advances in the biomedical treatment of DS and specifies the course
and contents of behavioral interventions in memory and language.
*Corresponding author:
Jean Adolphe Rondal
(jeanarondal@skynet.be)
Keywords: Down syndrome; Chromosome correction; Epigenetic regulation; Cognitive
Citation: Rondal JA. A holistic pharmacotherapy; Memory intervention; Language intervention
strategy for improving cognitive
development in children with Down
syndrome. Adv Neurol. 2025;4(1):1-10.
doi: 10.36922/an.3785
Received: May 29, 2024 1. Introduction
Revised: September 20, 2024 Down syndrome (DS) is estimated to have a natural incidence of approximately one case
in 800 living births. It is caused by the triplication of Hsa21 determining numerous gene
1
Accepted: October 23, 2024
dosage imbalances. This impairs the development of the brain and various body organs.
2
Published Online: November 18, Intellectual disability is the common hallmark ranging from mild to severe retardation.
2024
Copyright: © 2024 Author(s). DS exists in several forms: (1) Standard (complete) trisomy 21 (95% of the cases;
This is an Open-Access article karyotype 47, XN, +21); (2) mosaic trisomy 21 (1 – 2% of the cases) where only a portion
distributed under the terms of the of the cells carries one extra Hsa21; (3) Robertsonian (centric fusion; nonreciprocal)
Creative Commons Attribution
License, permitting distribution, translocations involving C21 are: C21 with C21, C13, C14, C15, and C22: formulae are
and reproduction in any medium, respectively 46, XN, t (21;21)(q10;q10), + 21, 46, XN, t (13;21)(q10;q10), +21, 46, XN t
provided the original work is
properly cited. (14;21)(q10;q10), + 21, 46, XN, t (15;21)(q10;q10), + 21, and 46, XN, t (21;22)(q10;q10),
+ 21, accounting for 3% of the cases; (4) partial T21 (<1% of the cases) results in only a
Publisher’s Note: AccScience
Publishing remains neutral with segment of Hsa21 being triplicated.
regard to jurisdictional claims in
published maps and institutional DS maps to a region on the long arm of Hsa21 corresponding to band 21q22 possibly
affiliations. containing a so-called DS-critical region the existence of which is contested. Hsa21

Volume 4 Issue 1 (2025) 1 doi: 10.36922/an.3785