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
Subscribe to Journal
Get full journal access for 1 year
only $9.92 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Tax calculation will be finalised during checkout.
Get time limited or full article access on ReadCube.
All prices are NET prices.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Sparrow S, Cicchetti D, Saulnier CJCP, MN: American Guidance Service. Vineland adaptive behavior scales–third edition. 2016.
Sparrow SS, Cicchetti DV, Balla DA. Vineland adaptive behavior scales Vineland-II: Survey forms manual: Pearson Minneapolis, MN; 2005.
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.
Constantino JN, Gruber CP. Social responsiveness scale: SRS-2: Western Psychological Services Torrance, CA; 2012.
American Psychiatric Association DS, American Psychiatric Association. Diagnostic and statistical manual of mental disorders: DSM-5. Washington, DC: American psychiatric association; 2013.
Dodd B, Zhu H, Crosbie S, Holm A, Ozanne A. Diagnostic evaluation of articulation and phonology (DEAP). London: The Psychological Corporation; 2002.
Duffy, JR. Motor speech disorders: substrates, differential diagnosis and management. St. Louis: MO: Mosby; 2013.
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.
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).
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.
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.
Robbins J, Klee TJJoS, Disorders H. Clin Assess oropharyngeal Mot Dev Young- Child. 1987;52:271–7.
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.
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.
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.
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).
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).
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.
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.
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.
Morgan AT, Murray E, Liegeois FJ. Interventions for childhood apraxia of speech. Cochrane Database Syst Rev. 2018;5:CD006278.
Morgan AT, Dodrill P, Ward EC. Interventions for oropharyngeal dysphagia in children with neurological impairment. Cochrane Database Syst Rev. 2012;10:CD009456.
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.
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 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.
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.
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
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
This article is cited by
European Journal of Human Genetics (2022)