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Expanding the speech and language phenotype in Koolen-de Vries syndrome: late onset and periodic stuttering a novel feature

European Journal of Human Genetics volume 31, pages 531–540 (2023)Cite this article

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Abstract

Speech and language impairment is core in Koolen-de Vries syndrome (KdVS), yet only one study has examined this empirically. Here we define speech, language, and functional/adaptive behaviour in KdVS; while deeply characterising the medical/neurodevelopmental phenotype in the largest cohort to date. Speech, language, literacy, and social skills were assessed using standardised measures, alongside an in-depth health and medical questionnaire. 81 individuals with KdVS were recruited (35 female, mean age 9y 10mo), 56 of whom harboured the typical 500–650 kb 17q21.31 deletion. The core medical phenotype was intellectual disability (largely moderate), eye anomalies/vision disturbances, structural brain anomalies, dental problems, sleep disturbance, musculoskeletal abnormalities, and cardiac defects. Most were verbal (62/81, 76.5%), while minimally-verbal communicators used alternative and augmentative communication (AAC) successfully in spite of speech production delays. Speech was characterised by apraxia (39/61, 63.9%) and dysarthria (28/61, 45.9%) in verbal participants. Stuttering was described in 36/47 (76.6%) verbal participants and followed a unique trajectory of late onset and fluctuating presence. Receptive and expressive language abilities were commensurate with one another, but literacy skills remained a relative weakness. Social competence, successful behavioural/emotional control, and coping skills were areas of relative strength, while communication difficulties impacted daily living skills as an area of comparative difficulty. Notably, KdVS individuals make communication gains beyond childhood and should continue to access targeted therapies throughout development, including early AAC implementation, motor speech therapy, language/literacy intervention, as well as strategies implemented to successfully navigate activities of daily living that rely on effective communication.

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Fig. 1
Fig. 2: Box and whisker plot of Vineland-3 adaptive behaviour domain standard scores according to genetic anomaly (i.e., comparing typical 17q21.31 deletions, larger 17q21.31 deletions, and KANSL1 variants) for individuals with KdVS in this cohort.
Fig. 3: Stuttering related characteristics in individuals with KdVS in this cohort.
Fig. 4: Prevalence of comorbidities.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgements

We would like to thank all individuals with Koolen-de Vries syndrome and their families who took part in this research study. Provided by National Health and Medical Research Council (NHMRC) Centre of Research Excellence in Speech and Language #1116976 (AM, DA).

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Author notes

  1. These authors contributed equally: David J. Amor, Angela T. Morgan.

Authors and Affiliations

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

    Miya St John, Olivia van Reyk, David J. Amor & Angela T. Morgan

  2. Department of Audiology and Speech Pathology, University of Melbourne, Melbourne, VIC, Australia

    Miya St John & Angela T. Morgan

  3. Department of Human Genetics, Radboud Institute for Molecular Life Sciences and Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands

    David A. Koolen & Bert B. A. de Vries

  4. Department of Paediatrics, University of Melbourne, Melbourne, VIC, Australia

    David J. Amor

  5. Speech Pathology Department, Royal Children’s Hospital, Melbourne, VIC, Australia

    Angela T. Morgan

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Contributions

MSJ: collected data, analysed data, interpreted data and wrote/edited manuscript. OvR, DAK and BBAdV: collected data, analysed data and edited manuscript. DJA and ATM: designed and conceptualised the study, interpreted data, directed the project and wrote/edited manuscript.

Corresponding author

Correspondence to Angela T. Morgan.

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Ethical approval

Ethical approval was obtained through the Royal Children’s Hospital, Melbourne, Human Research Ethics Committee (HREC #37353). Written informed consent was obtained from the participant or their parents/legal guardian in the case of minors or adults with intellectual disabilities.

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The authors declare no competing interests.

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St John, M., van Reyk, O., Koolen, D.A. et al. Expanding the speech and language phenotype in Koolen-de Vries syndrome: late onset and periodic stuttering a novel feature. Eur J Hum Genet 31, 531–540 (2023). https://doi.org/10.1038/s41431-022-01230-7

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