Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Social motivation a relative strength in DYRK1A syndrome on a background of significant speech and language impairments

European Journal of Human Genetics volume 30, pages 800–811 (2022)Cite this article

Subjects

Abstract

Speech and language impairments are commonly reported in DYRK1A syndrome. Yet, speech and language abilities have not been systematically examined in a prospective cohort study. Speech, language, social behaviour, feeding, and non-verbal communication skills were assessed using standardised tools. The broader health and medical phenotype was documented using caregiver questionnaires, interviews and confirmation with medical records. 38 individuals with DYRK1A syndrome (23 male, median age 8 years 3 months, range 1 year 7 months to 25 years) were recruited. Moderate to severe intellectual disability (ID), autism spectrum disorder (ASD), vision, motor and feeding impairments were common, alongside epilepsy in a third of cases. Speech and language was disordered in all participants. Many acquired some degree of verbal communication, yet few (8/38) developed sufficient oral language skills to rely solely on verbal communication. Speech was characterised by severe apraxia and dysarthria in verbal participants, resulting in markedly poor intelligibility. Those with limited verbal language (30/38) used a combination of sign and graphic augmentative and alternative communication (AAC) systems. Language skills were low across expressive, receptive, and written domains. Most had impaired social behaviours (25/29). Restricted and repetitive interests were most impaired, whilst social motivation was a relative strength. Few individuals with DYRK1A syndrome use verbal speech as their sole means of communication, and hence, all individuals need early access to tailored, graphic AAC systems to support their communication. For those who develop verbal speech, targeted therapy for apraxia and dysarthria should be considered to improve intelligibility and, consequently, communication autonomy.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to the full article PDF.

USD 39.95

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Vineland Adaptive Behaviour Scales, Second and Third Edition [16, 17] domains (n = 32).
Fig. 2: Performance on Child Oral and Motor Proficiency Scale.
Fig. 3: Average T scores on the Social Responsiveness Scale, Second Edition [19].
Fig. 4: Dysarthric speech features.

Similar content being viewed by others

Data availability

The datasets generated during and/or analysed during the current study are not publicly available because families did not consent to this, but are available from the corresponding author on reasonable request and if families provide consent.

References

  1. Guedj F, Pereira PL, Najas S, Barallobre M-J, Chabert C, Souchet B, et al. DYRK1A: a master regulatory protein controlling brain growth. Neurobiol Dis. 2012;46:190–203.

    Article  CAS  Google Scholar 

  2. Lin YC, Frei JA, Kilander MB, Shen W, Blatt GJ. A subset of autism-associated genes regulate the structural stability of neurons. Front Cell Neurosci. 2016;17:263.

    Google Scholar 

  3. Arranzranz J, Balducci E, Arató K, Sánchez-Elexpuru G, Najas S, Parras A, et al. Impaired development of neocortical circuits contributes to the neurological alterations in DYRK1A haploinsufficiency syndrome. Neurobiol Dis. 2019;127:210–22.

    Article  Google Scholar 

  4. Ji J, Lee H, Argiropoulos B, Dorrani N, Mann J, Martinez-Agosto JA, et al. DYRK1A haploinsufficiency causes a new recognizable syndrome with microcephaly, intellectual disability, speech impairment, and distinct facies. Eur J Hum Genet: EJHG. 2015;23:1473–81.

    Article  CAS  Google Scholar 

  5. Brignell A, Chenausky KV, Song H, Zhu J, Suo C, Morgan AT. Communication interventions for autism spectrum disorder in minimally verbal children, Cochrane Database Syst Rev. 2018;11:CD012324.

    PubMed  Google Scholar 

  6. van Bonn Bon BW, Coe BP, Bernier R, Green C, Gerdts J, Witherspoon K, et al. Disruptive de novo mutations of DYRK1A lead to a syndromic form of autism and ID. Mol Psychiatry. 2016;21:126–32.

    Article  Google Scholar 

  7. Earlrl RK, Turner TN, Mefford HC, Hudac CM, Gerdts J, Eichler EE, et al. Clinical phenotype of ASD-associated DYRK1A haploinsufficiency. Mol Autism. 2017;8:1–15.

    Google Scholar 

  8. Meissner LE, Macnamara EF, D’Souza P, Yang J, Vezina G, Network UD, et al. DYRK1A pathogenic Var two patients syndromic Intellect Disabil A Rev Lit. 2020;8:e1544.

    CAS  Google Scholar 

  9. Murray CR, Abel SN, McClure MB, Foster J. Novel causative variants in DYRK1A, KARS, and KAT6A associated with intellectual disability and additional phenotypic features. J Pediatr Genet. 2017;6:77–83.

    Article  CAS  Google Scholar 

  10. Qiao F, Shao B, Wang C, Wang Y, Zhou R, Liu G, et al. A de novo mutation in DYRK1A causes syndromic intellectual disability: a Chinese case report. Front Genet. 2019;10:1194.

    Article  Google Scholar 

  11. Valetto A, Orsini A, Bertini V, Toschi B, Bonuccelli A, Simi F, et al. Molecular cytogenetic characterization of an interstitial deletion of chromosome 21 (21q22. 13q22. 3) in a patient with dysmorphic features, intellectual disability and severe generalized epilepsy. Eur J Med Genet. 2012;55:362–6.

    Article  Google Scholar 

  12. Courraud J, Chater-Diehl E, Durand B, Vincent M, del Mar Muniz Moreno M, Boujelbene I, et al. Integrative approach to interpret DYRK1A variants, leading to a frequent neurodevelopmental disorder. Genet Med. 2021;23:2150–9.

    Article  CAS  Google Scholar 

  13. Mei C, Fedorenko E, Amor DJ, Boys A, Hoeflin C, Carew P, et al. Deep phenotyping of speech and language skills in individuals with 16p11. 2 deletion. Eur J Hum Genet: EJHG. 2018;26:676–86.

    Article  CAS  Google Scholar 

  14. Morganorgan A, Braden R, Wong M, Colin E, Amor D, Liégeois F, et al. Speech and language deficits are central to SETBP1 haploinsufficiency disorder. Eur J Hum Genet: EJHG. 2021;29:1–10.

    Google Scholar 

  15. Pados BF, Thoyre SM, Park J. Age‐based norm‐reference values for the Child Oral and Motor Proficiency Scale. Acta Paediatrica. 2018;107:1427–32.

    Article  Google Scholar 

  16. Sparrow S, Cicchetti D, Saulnier CJCP, MN: American Guidance Service. Vineland adaptive behavior scales–third edition. 2016.

  17. Sparrow SS, Cicchetti DV, Balla DA. Vineland adaptive behavior scales Vineland-II: Survey forms manual: Pearson Minneapolis, MN; 2005.

  18. Sigafoos J, Woodyatt G, Keen D, Tait K, Tucker M, Roberts-Pennel D. The inventory of potential communicative acts. Enhancing everyday communication for children with disabilities. Paul H Brookes Publishing; 2006, p. 137–50.

  19. Constantino JN, Gruber CP. Social responsiveness scale: SRS-2: Western Psychological Services Torrance, CA; 2012.

  20. American Psychiatric Association DS, American Psychiatric Association. Diagnostic and statistical manual of mental disorders: DSM-5. Washington, DC: American psychiatric association; 2013.

  21. Dodd B, Zhu H, Crosbie S, Holm A, Ozanne A. Diagnostic evaluation of articulation and phonology (DEAP). London: The Psychological Corporation; 2002.

  22. Duffy, JR. Motor speech disorders: substrates, differential diagnosis and management. St. Louis: MO: Mosby; 2013.

  23. Morgan AT, Masterton R, Pigdon L, Connelly A, Liegeois FJJB. Functional magnetic resonance imaging of chronic dysarthric speech after childhood brain injury: reliance on a left-hemisphere compensatory network. Brain: J Neurol. 2013;136:646–57.

    Article  Google Scholar 

  24. American Speech-Language Hearing Association. Childhood apraxia of speech [Internet]. Rockville, MD: ASHA; 2022. Available from: https://www.ash.org/public/speech/disorders/childhood-apraxia-of-speech/ (accessed 16 March 2022).

  25. Braden RO, Amor DJ, Fisher SE, Mei C, Myers CT, Mefford H, et al. Severe speech impairment is a distinguishing feature of FOXP1‐related disorder. Dev Med Child Neurol. 2021;63:1417–26.

    Article  Google Scholar 

  26. Bradenraden RO, Boyce JO, Stutterd CA, Pope K, Goel H, Leventer RJ, et al. Speech, Language, and Oromotor Skills in Patients With Polymicrogyria. Neurology. 2021;96:e1898–e912.

    Article  Google Scholar 

  27. Robbins J, Klee TJJoS, Disorders H. Clin Assess oropharyngeal Mot Dev Young- Child. 1987;52:271–7.

    CAS  Google Scholar 

  28. McLeod S, Crowe K, Shahaeian AJL. Intelligibility in Context Scale: Normative and validation data for English-speaking preschoolers. Lang, Speech, Hearing Serv Sch. 2015;46:266–76.

    Article  Google Scholar 

  29. Møllerøller RS, Kübart S, Hoeltzenbein M, Heye B, Vogel I, Hansen CP, et al. Truncation of the Down syndrome candidate gene DYRK1A in two unrelated patients with microcephaly. Am J Hum Genet. 2008;82:1165–70.

    Article  Google Scholar 

  30. Luco SM, Pohl D, Sell E, Wagner JD, Dyment DA, Daoud HJBmg. Case report of novel DYRK1A mutations in 2 individuals with syndromic intellectual disability and a review of the literature. BMC Med Genet. 2016;17:1–8.

    Article  Google Scholar 

  31. University of Washington. TIGER study [Internet]. Seattle, WA: University of Washington Autism Centre; 2022. Available from: https://depts.washington.edu/uwautism/research-projects/tiger-study/ (accessed 16 March 2022).

  32. Simon’s Foundation. Simon’s searchlight [Internet]. New York City, NY: Simon’s Foundation; 2022. Available from: https://www.simonssearchlight.org/ (accessed 16 March 2022).

  33. Widowati EW, Ernst S, Hausmann R, Müller-Newen G, Becker WJBo. Functional characterization of DYRK1A missense variants associated with a syndromic form of intellectual deficiency and autism. Biol Open. 2018;7:bio032862.

    Article  Google Scholar 

  34. Aydin O, Diken IHJE, Ti Autism, Disabilities D. Stud comparing augmentative alternative Commun Syst (AAC) Appl Individ autism Spectr Disord: A Syst Rev meta-Anal. 2020;55:119–41.

    Google Scholar 

  35. Pennington L, Parker NK, Kelly H, Miller N. Speech therapy for children with dysarthria acquired before three years of age. Cochrane Database Syst Rev. 2016;7:CD006937.

  36. Morgan AT, Murray E, Liegeois FJ. Interventions for childhood apraxia of speech. Cochrane Database Syst Rev. 2018;5:CD006278.

    Google Scholar 

  37. Morgan AT, Dodrill P, Ward EC. Interventions for oropharyngeal dysphagia in children with neurological impairment. Cochrane Database Syst Rev. 2012;10:CD009456.

    Google Scholar 

  38. Thurm A, Farmer C, Salzman E, Lord C, Bishop SJFip. State of the field: differentiating intellectual disability from autism spectrum disorder. Front Psychiatry. 2019;10:526.

    Article  Google Scholar 

Download references

Acknowledgements

Our sincere thanks to all the children, young adults and their families who took part in this project. A special thanks to the DYRK1A society for their assistance with recruitment and support of the project.

Funding

Funding was provided by National Health and Medical Research Council (NHMRC) Practitioner Fellowship #1105008 (AM); NHMRC Investigator Grant #1195955. NHMRC Centre of Research Excellence in Speech and Language Neurobiology #1116976 (ATM, DJA). This work was supported by the Victorian Government’s Operational Infrastructure Support Program.

Author information

Author notes

  1. These authors contributed equally: Lottie D. Morison, Ruth O. Braden.

  2. These authors jointly supervised this work: Bregje W. M. van Bon, Angela T. Morgan.

Authors and Affiliations

  1. Murdoch Children’s Research Institute, Melbourne, VIC, Australia

    Lottie D. Morison, Ruth O. Braden, David J. Amor, Amanda Brignell & Angela T. Morgan

  2. The University of Melbourne, Melbourne, VIC, Australia

    David J. Amor & Angela T. Morgan

  3. Royal Children’s Hospital, Melbourne, VIC, Australia

    David J. Amor & Angela T. Morgan

  4. Monash University, Melbourne, VIC, Australia

    Amanda Brignell

  5. Australian Catholic University, Melbourne, VIC, Australia

    Amanda Brignell

  6. Radboud University Medical Centre, Nijmegen, Netherlands

    Bregje W. M. van Bon

Authors
  1. Lottie D. Morison
    View author publications

    Search author on:PubMed Google Scholar

  2. Ruth O. Braden
    View author publications

    Search author on:PubMed Google Scholar

  3. David J. Amor
    View author publications

    Search author on:PubMed Google Scholar

  4. Amanda Brignell
    View author publications

    Search author on:PubMed Google Scholar

  5. Bregje W. M. van Bon
    View author publications

    Search author on:PubMed Google Scholar

  6. Angela T. Morgan
    View author publications

    Search author on:PubMed Google Scholar

Contributions

LDM: generated data, analysed data, interpreted data, wrote manuscript. ROB: generated data, analysed data, interpreted data, wrote manuscript. DJA: analysed data, interpreted data. AB: analysed data, interpreted data. BWMVB: designed and conceptualised study, wrote manuscript. ATM: designed and conceptualised study, directed project, interpreted data, wrote manuscript.

Corresponding author

Correspondence to Angela T. Morgan.

Ethics declarations

Competing interests

The authors declare no competing interests.

Ethics approval and consent to participate

Ethics approval was obtained from the Royal Children’s Hospital, Melbourne, Human Research Ethics Committee (HREC 37353A). Participants’ caregivers provided informed electronic consent to participate in the study.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Morison, L.D., Braden, R.O., Amor, D.J. et al. Social motivation a relative strength in DYRK1A syndrome on a background of significant speech and language impairments. Eur J Hum Genet 30, 800–811 (2022). https://doi.org/10.1038/s41431-022-01079-w

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Version of record:

  • Issue date:

  • DOI: https://doi.org/10.1038/s41431-022-01079-w

This article is cited by

Search

Advanced search

Quick links