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CDK13-related disorder: a deep characterization of speech and language abilities and addition of 33 novel cases

European Journal of Human Genetics (2023)Cite this article

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Abstract

Speech and language impairments are central features of CDK13-related disorder. While pathogenic CDK13 variants have been associated with childhood apraxia of speech (CAS), a systematic characterisation of communication has not been conducted. Here we examined speech, language, non-verbal communication skills, social behaviour and health and development in 41 individuals with CDK13-related disorder from 10 countries (male = 22, median-age 7 years 1 month, range 1–25 years; 33 novel). Most participants used augmentative and alternative communication (AAC) in early childhood (24/41). CAS was common (14/22). Performance varied widely across intellectual ability, social behaviour and expressive language skills, with participants ranging from within average through to the severely impaired range. Receptive language was significantly stronger than expressive language ability. Social motivation was a relative strength. In terms of a broader health phenotype, a quarter had one or more of: renal, urogenital, musculoskeletal, and cardiac malformations, vision impairment, ear infections and/or sleep disturbance. All had gross and fine motor impairments (41/41). Other conditions included mild-moderate intellectual disability (16/22) and autism (7/41). No genotype-phenotype correlations were found. Recognition of CAS, a rare speech disorder, is required to ensure appropriately targeted therapy. The high prevalence of speech and language impairment underscores the importance of tailored speech therapy, particularly early access to AAC supports.

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Fig. 1: Lollipop chart of CDK13 missense variants in this cohort.
Fig. 2: The Vineland Adaptive Behaviour Scales domain scores of participants (n = 36) with c.2525 A > G, p.Asn842Ser missense variants (n = 15) and other pathogenic variants (n = 21).
Fig. 3: Social behaviour domains on the social responsiveness scale second edition (T scores) (n = 28).
Fig. 4: Motor speech disorders in assessed participants (n = 22).

Data availability

The datasets generated and analysed during this study are not publicly available because participants have not given permission for data to be made public but may be requested from the corresponding author (A.T.M) who could go back to the participants to request data sharing. Genotypic data were submitted to Decipher (https://decipher.sanger.ac.uk/).

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Acknowledgements

Sincere thanks to the children, families and clinicians who took part in this project.

Funding

This work was supported by a National Health and Medical Research Council (NHMRC) Centre of Research Excellence in Speech and Language Neurobiology (CRE-SLANG) #1116976 awarded to A.T.M.; NHMRC Practitioner Fellowship #1105008 awarded to A.T.M., and an NHMRC Investigator grant #1195955 awarded to A.T.M. This work is also supported by the Victorian Government’s Operational Infrastructure Support Program.

Author information

Authors and Affiliations

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

    Lottie D. Morison, Olivia van Reyk, Elana Forbes, David J. Amor & Angela T. Morgan

  2. School of Psychological Sciences, Monash University, Melbourne, VIC, Australia

    Elana Forbes

  3. Génétique Clinique, Départment de Génétique Médicale, Maladies Rares et Médecine Personnalisée, CHU Montpellier, Montpellier University, Centre de Référence Anomalies du Développement SOOR, Montpellier, France

    Flavien Rouxel & David Geneviève

  4. Centre de Référence Anomalies du Développment et Syndromes Malformatifs, FHU TRANSLAD, CHU Dijon, Dijon, France

    Laurence Faivre

  5. Genetics of Developmental Disorders, INSERM – Bourgogne Franche-Comté Univeristy, Dijon, France

    Laurence Faivre

  6. Cancer Council Victoria, Melbourne, VIC, Australia

    Fiona Bruinsma

  7. Service de génétique médicale, CHU Nantes, 9 quai Moncousu, Nantes, France

    Marie Vincent

  8. Unit of Medical Genetics, CHU La Réunion, Saint Pierre, France

    Marie-Line Jacquemont

  9. Lucile Packard Children’s Hospital, Stanford Children’s Health, Palo Alto, CA, USA

    Natalie L. Dykzeul

  10. Department of Paediatrics, The University of Melbourne, Melbourne, VIC, Australia

    David J. Amor

  11. The Royal Children’s Hospital, Melbourne, VIC, Australia

    David J. Amor & Angela T. Morgan

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

    Angela T. Morgan

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Contributions

LDM: generated data, analysed data, interpreted data, wrote manuscript. OV: generated data, analysed data, interpreted data, revised manuscript. EF: analysed data, interpreted data, revised manuscript. FR: generated data, analysed data, revised manuscript. LF: generated data, analysed data, revised manuscript. FB: generated data, analysed data, revised manuscript. MV: generated data, analysed data, revised manuscript. MJ: generated data, analysed data, revised manuscript. NLD: generated data, analysed data, revised manuscript. DG: generated data, analysed data, revised manuscript. DJA: generated data, analysed data, interpreted data, revised manuscript. ATM: designed and conceptualised study, directed project, generated data, analysed data, interpreted data, wrote manuscript.

Corresponding author

Correspondence to Angela T. Morgan.

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The authors declare no competing interests.

Ethics approval

Ethics approval was obtained from the Royal Children’s Hospital, Melbourne, Human Research Ethics Committee (HREC 37353A). Adult participants and caregivers of child participants provided informed consent to participate in the study and for results of this study to be published.

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Morison, L.D., van Reyk, O., Forbes, E. et al. CDK13-related disorder: a deep characterization of speech and language abilities and addition of 33 novel cases. Eur J Hum Genet (2023). https://doi.org/10.1038/s41431-022-01275-8

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