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Speech and language phenotype in Phelan-McDermid (22q13.3) syndrome

European Journal of Human Genetics volume 29, pages 564–574 (2021)Cite this article

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A Correction to this article was published on 15 March 2021

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Abstract

Communication difficulties are a core feature of Phelan-McDermid syndrome (PMS). However, a specific speech and language phenotype has not been delineated, preventing prognostic counselling and development of targeted therapies. We examined speech, language, social and functional communication abilities in 21 individuals with PMS (with SHANK3 involvement), using standardised assessments. Mean age was 9.7 years (SD 4.1) and 57% were female. Deletion size ranged from 41 kb to 8.3 Mb. Nine participants (45%) were non-verbal. Four (19%) had greater verbal ability, speaking in at least 4–5 word sentences, but with speech sound errors. Standard scores for receptive and expressive language were low (typically >3 SD below the mean). Language age equivalency was 13–16 months on average (range 2–53 months). There was a significant association between deletion size and the ability to use phrases. Participants with smaller deletion sizes were more likely to be able to use phrases (odds ratio: 0.36, 95% CI: 0.14–0.95, p = 0.040). Adaptive behaviour (life skills) was low in all areas (>2 SD below mean). Scores in communication were markedly lower than for daily living (p = 0.008) and socialisation (p < 0.001). A common linguistic profile was characterised by severe impairment across receptive, expressive and social language domains. Yet data indicated greater communicative intent than appeared to be capitalised by current therapies. Early implementation of augmentative (e.g. computer-assisted) modes of communication, alongside promotion of oral language, is essential to harness this intent, accelerate language development and reduce frustration. Future trials should examine the added benefit of targeted speech motor interventions in those with greater verbal capacity.

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Fig. 1
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Fig. 4: Median deletion size (and interquartile range) in Megabases for the groups who did and did not use phrases.

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Acknowledgements

We thank the individuals with PMS and their families for their participation. We also thank Megan Toole for her assistance with recruitment through the Phelan McDermid Syndrome Foundation of Australia.

Funding

Funding was provided by National Health and Medical Research Council (NHMRC) Practitioner Fellowship #1105008 (A.M.); NHMRC Centre of Research Excellence in Speech and Language Neurobiology #1116976 awarded to A.M., D.A.

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Authors and Affiliations

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

    Amanda Brignell, Daisy A. Sheppard, David J. Amor & Angela T. Morgan

  2. University of Melbourne, Melbourne, Australia

    Amanda Brignell, Conway Gu, Daisy A. Sheppard, David J. Amor & Angela T. Morgan

  3. Griffith University, Brisbane, Australia

    Alison Holm

  4. Telethon Kids Institute, Perth, Australia

    Bronwyn Carrigg

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  1. Amanda Brignell
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Correspondence to Angela T. Morgan.

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Brignell, A., Gu, C., Holm, A. et al. Speech and language phenotype in Phelan-McDermid (22q13.3) syndrome. Eur J Hum Genet 29, 564–574 (2021). https://doi.org/10.1038/s41431-020-00761-1

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