AccScience Publishing / AN / Online First / DOI: 10.36922/an.3785
Submit to AN
Cite this article
28
Download
182
Views
Journal Browser
Volume | Year
Issue
Search
Forthcoming Issue
Current Issue
View All
News and Announcements
View All
REVIEW ARTICLE

A holistic strategy for improving cognitive development in children with Down syndrome

Jean Adolphe Rondal*
Show Less
1 Department of Cognitive Sciences, Cognitive Neuroscience, Faculty of Psychology, University of Liège, Belgium
Advanced Neurology, 3785 https://doi.org/10.36922/an.3785
Submitted: 29 May 2024 | Accepted: 23 October 2024 | Published: 18 November 2024
© 2024 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
Download PDF
Cite
XML
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.

Keywords
Down syndrome
Chromosome correction
Epigenetic regulation
Cognitive pharmacotherapy
Memory intervention
Language intervention
Funding
None.
Conflict of interest
The author declares no conflicts of interest.
References
  1. Bull M. Down syndrome. N Engl J Med. 2020;382:2344- 2352. doi: 10.1056/NEJMra1706537

 

  1. Hughes-McCormack L, McGowan R, Pell J, et al. Birth incidence, deaths and hospitalisations of children and young people with Down syndrome, 1990-2015: Birth cohort study. Brit Med J Open. 2019;10:e033770. doi: 10.1136/bmjopen-2019-033770

 

  1. Aim A, Kumar A, Multhuswamy S, et al. Down syndrome: An insight of the disease. J Biomed Sci. 2015;22:41-50. doi: 10.1186/s12929-015-0138-y

 

  1. Sun X, Lu J, Ma X. An efficient method for noninvasive prenatal diagnosis of fetal. Risomy 13, trisomy 18, and trisomy 21. PLoS One. 2019;14:1.doi: 10.1371/journal.pone.0215368.2019

 

  1. Gray K, Wilkins-Haug L. Have we done our last amniocentesis? Updates on cell-free DNA for Down syndrome screening. Pediatr Radiol. 2018;48:461-470. doi: 10.1007/s00247-017-3958-y

 

  1. De Graaf G, Buckley F, Skotko B. Estimation of the number of people with Down syndrome in Europe. Europ J Hum Gen. 2021;29:402-410. doi: 10.1038/s41431-020-00748-y

 

  1. De Graaf G, Buckley F, Skotko B. Estimation of the number of people with Down syndrome in the United States. Gen Med. 2016;201:439-447. doi: 10.1038/gim.216.127

 

  1. O’Leary L, Cooper S, McCormack H. Early death and causes of death of people with Down syndrome: A systematic review. J Appl Res Intellect Disabil. 2018;31:325-342. doi: 10.1111/jar.12417

 

  1. Abukhaled Y, Hatab K, Awadhalla M, et al. Understanding the genetic mechanisms and cognitive impairments in Down syndrome: Towards a holistic approach. J Neurol. 2024;271:87-104. doi: 10.1007/s00415-023-11890-0

 

  1. Amano T, Jeffries E, Amano M, Ko AC, Yu H, Ko MS. Correction of down syndrome and edwards syndrome aneuploidies in human cell cultures. DNA Res. 2015;22: 331-342. doi: 10.1093/dnares/dsv016

 

  1. Li L, Chang K, Wang P, et al. Trisomy correction in Down syndrome induced pluripotent stem cells. Cell Stem Cell. 2012;11:615-619. doi: 10.1016/j.stem.2012.08.004

 

  1. Jiang J, Jing Y, Cost G, et al. Translating dosage compensation to trisomy 21. Nature. 2013;500:296-300. doi: 10.1038/nature12394

 

  1. Czerminsky J, Lawrence J. Silencing trisomy 21 with XIST in neural stem cells promotes neuronal differentiation. Dev Cell. 2020;52:294-308. doi: 10.1016/j.devcel.2019.12.015

 

  1. Dumont M. Qualité et sélection des embryons. J Gynécol Obstét Biol Reprod. 2008;17:S9-S13. doi: 10.1016/S0368-2315(08)73844-4

 

  1. Aït Yahya-Graison E, Aubert J, Dauphinot L, et al. Classification of human chromosome 21 gene-expression variations in Down syndrome: Impact on disease phenotypes. Am J Hum Genet. 2007;81:475-491. doi: 10.1086/520000

 

  1. Tejedor F, Hammerle B. MNB/DYRK1A as a multiple regulator of neuronal development. FEBS J. 2010;278: 223-235. doi: 10.1111/j.1742-4658.2010.07954.x

 

  1. Chapman L, Ramnarine I, Zemke D, et al. Gene expression studies in Down syndrome: What do they tell us about disease phenotypes? Int J Mol Sci. 2024;25:2968. doi: 10.3390/ijms25052968

 

  1. Guedj F, Sébrié C, Rivals I, et al. Green tea polyphenols rescue of brain defects induced by overexpression of DYRK1A. PLoS One. 2009;4:e4606. doi: 10.1371/journal.pone.0004606

 

  1. Stagni F, Giacomini A, Emili M, et al. Short-and long-term effects of neonatal pharmacotherapy with epigallocatechin- 3-gallate on hippocampal development in the Ts65Dn mouse model of down syndrome. Neuroscience. 2016;333:277-301. doi: 10.1016/j.neuroscience.2016.07.031

 

  1. Starbuck J, llambrich S, Gonzales R, et al. Green tea extracts containing epigallocatechin-3-gallate modulate facial development in Down syndrome. Sci Rep. 2021;11:4715. doi: 10.1038/s41598-021-83757-1

 

  1. De la Torre R, De Sola S, Hernandez G, et al. Safety and efficacy of cognitive training plus epigallocatechin-3- gallate in young adults with Down’s syndrome (TESDAD): A double-blind, randomized, placebo-controlled, phase 2 trial. Lancet Neurol. 2016;15:801-810. doi: 10.1016/S1474-4422(16)30034-5

 

  1. Prandini P, Deutsch S, Lyle R, et al. Natural gene-expression variation in Down syndrome modulates the outcome of gene dosage imbalance. Am J Hum Genet. 2007;81:252-263. doi: 10.1086/519248

 

  1. Hunter S, Hendrix J, Freeman J, Allen MA. Transcription dosage compensation does not occur in Down syndrome. BMC Biol. 2023;21:228. doi: 10.1186/s12915-023-01700-4

 

  1. Donovan M, Eduthan N, Smith K, et al. Variegated overexpression of chromosome 21 genes reveals molecular and immune subtypes of down syndrome. Nat Com. 2024;15:5473. doi: 10.1038/s41467-024-49781-1

 

  1. Takashima S, Iida K, Mito T, Arima M. Dendritic and histochemical development and ageing in patients with Down’s syndrome. J Intellect Disabil Res. 1994;3:265-273. doi: 10.1111/j.1365-2788.1994.tb00394.x

 

  1. Qiu JJ, Liu YN, Wey H, Zeng F, Yan JB. Single-cell RNA sequencing of neural stem cells derived from human trisomic iPSCs reveals the abnormalities during neural differentiation of down syndrome. Front Mol Neurosci. 2023;16:1137.doi: 10.3389/fnmol.2023;1137123

 

  1. Martinez J, Piciw J, Crockett M, et al. Transcriptional consequences of trisomy 21 on neural induction. Front Cell Neurosci. 2024;18:1341141. doi: 10.3389/fncel.2024.1341141

 

  1. Stagni F, Bartesaghi R. The challenging pathway of treatment for neurogenesis impairment in Down syndrome: Achievements and perspectives. Front Cell Neurosci. 2022;16:903729. doi: 10.3389/fncel.2022.903729

 

  1. Gotti S, Caricati E, Panzica G. Alterations of brain circuits in DS murine models. J Chem Neuroanat. 2011;42:317-326. doi: 10.1016/j.jchemneu.2011.09.002

 

  1. Bartesaghi R, Vicari S, Mobley W. Prenatal and postnatal pharmacotherapy in Down syndrome: The search to prevent or ameliorate neurodevelopment and neurodegenerative disorders. Ann Rev Pharm Toxicol. 2022;62:211-233. doi: 10.1146/annurev-pharmtox-041521-103641

 

  1. Baddeley A. Human Memory: Theory and Practice. London: Psychology Press; 1997.

 

  1. Jarrold C, Baddeley A. Short-term memory for verbal and visuo-spatial information in down syndrome. Cogn Neuropsychiatry. 1997;2:101-122. doi: 10.1080/135468097396351

 

  1. Hulme C, Mackenzie S. Working Memory and Severe Learning Difficulties. Hove, UK: Erlbaum; 1992. doi: 10.4324/9781315795737

 

  1. Rondal JA. Exceptional Language Development in Down Syndrome. New York: Cambridge University Press; 1995. doi: 10.1017/CBO9780511582189

 

  1. Pennington B, Moon J, Edgin J, et al. The neuropsychology of Down syndrome: Evidence for hippocampal dysfunction. Child Dev. 2003;74:75-93. doi: 10.1111/1467-8624.00522

 

  1. Jarrold C, Baddeley A, Philips C. Long-term memory for verbal and visual information in Down syndrome and Williams syndrome: Performance on the Doors and People test. Cortex. 2007;43:233-247. doi: 10.1016/s0010-9452(08)70478-7

 

  1. Vicari S, Belluci S, Carlesimo G. Implicit and explicit memory: A functional dissociation in persons with down syndrome. Neuropsychologia. 2000;38:240-251. doi: 10.1016/s0028-3932(99)00081-0

 

  1. Fujii T, Moscovitch M, Nadel L Memory consolidation, retrograde amnesia, and the temporal lobe. In: Boller F, Grafman JH, editors. Handbook of Neuropsychology. Vol. 2. Amsterdam: Elsevier; 2000. p. 233-250.

 

  1. Rossato J, Bevilacqua L, Izquiero L, et al. Dopamine controls persistence of long-term memory storage. Science. 2009;325:1017-1020. doi: 10.1126/science.1172545

 

  1. Pinter J, Eliez S, Schmitt J, Capone GT, Reiss AL. Neuroanatomy of down’s syndrome: A high-resolution MRI study. Am J Psychiatry. 2001;158:1659-1665. doi: 10.1176/appi.ajp.158.10.1659

 

  1. Ullman M. Contributions of memory circuits to language: The declarative/procedural model. Cognition. 2004;92: 231-270. doi: 10.1016/j.cognition.2003.10.008

 

  1. Devenny D. The contribution of memory to the behavioral phenotype of down syndrome. In Rondal JA, Perera J, editors. Down Syndrome. Neurobehavioural Specificity. Chichester, UK: Wiley; 2006. p. 85-100.

 

  1. Démonet JF, Planton S. Langage et cerveau: Vingt-ans d’imagerie fonctionnelle. Rev Française Linguistique Appl. 2012;17(2):9-18.

 

  1. Bartesaghi R. Brain circuit pathology in Down syndrome: From neurons to neural networks. Rec Neurosci. 2022;34: 365-423. doi: 10.1515/revneuro-2022-0067

 

  1. Kaczorowska N, Kaczorowski K, Laskowska J, Mikulewicz M. Down syndrome as a cause of abnormalities in the craniofacial region: A systematic literature review. Adv Clin Exp Med. 2019;28:1587-1592. doi: 10.17219/acem/112785

 

  1. Diaz-Quevedo A, Castillo-Quispe H, Atoche-Socola K, Atoche-Socola KJ, Arriola-Guillén LE. Evaluation of the craniofacial and oral characteristics of individuals with Down syndrome: A review of the literature. J Stomatol Oral Maxillofac Surg. 20211;22:583-587. doi: 10.1016/j.jormas.2021.01.007

 

  1. Alessandri-Bonetti A, Guglielmi F, Mollo A, et al. Prevalence of malocclusions in Down syndrome population: A cross-sectional study. Medicina (Kaunas). 2023;59:1657. doi: 10.3390/medicina59091657

 

  1. Redhead Y, Gibbins D, Elola E, et al. Craniofacial dysmorphology in Down syndrome is caused by increased dosage of Dyrk1a and at least three other genes. Development. 2023;150(8):dev201077. doi: 10.1242/dev.201077

 

  1. Llambrich Ferré S. Integrated Development and Modulation of the Brain, Bones and Cognition in the Context of Down Syndrome. Doctoral Dissertation, Katholieke Universiteit Leuven, School of Biomedical Sciences; 2023.

 

  1. Stoel-Gammon C. Speech acquisition and approaches to intervention; In Rondal JA, Buckley S, editors. Speech and Language Intervention in Down Syndrome. London: Whurr, 2003. p. 49-62.

 

  1. Deckers SR. Lexical Development in Children with Down Syndrome: A Communicative Perspective. Nijmegen: Behavioral Science Institute, Radboud University; 2022.

 

  1. Rondal JA. Morphosyntactic training and intervention. In: Rondal JA, Buckley S, editors. Speech and Language Intervention in Down Syndrome. London: Whurr, 2003. p. 86-97, p. 188-194.

 

  1. Hughes J. Teaching reading skills to children with Down syndrome. Down Syndr News Update. 2006;6(2):62-65. doi: 10.3104/practice.349

 

  1. Rondal JA. Sentence discontinuous constituents and implicit learning limitations in down syndrome. Europ J Int Dis. 2017;11:1-14.

 

  1. Moraleda-Sepulveda E, López-Resa P, Pulido-Garcia N. Language intervention in Down syndrome: A systematic review. Int J Environ Res Public Health. 2022;19:6043. doi: 10.3390/ijerph19106043

 

  1. Smith E, Hokstad S, Naess KA. Children with Down syndrome can benefit from language interventions; Results from a systematic review and meta-analysis. J Commun Dis. 2020;85:105992. doi: 10.1016/j.jcomdis.2020.105992
Share
Back to top
Advanced Neurology, Electronic ISSN: 2810-9619 Print ISSN: 3060-8589, Published by AccScience Publishing
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here
Accept