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

Eur J Hum Genet. 2021 Apr;29(4):564-574. doi: 10.1038/s41431-020-00761-1. Epub 2020 Dec 8.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Chromosome Deletion
  • Chromosome Disorders / genetics*
  • Chromosome Disorders / pathology
  • Chromosomes, Human, Pair 22 / genetics
  • Female
  • Humans
  • Language Development*
  • Male
  • Nerve Tissue Proteins / genetics
  • Phenotype
  • Social Behavior

Substances

  • Nerve Tissue Proteins
  • SHANK3 protein, human

Supplementary concepts

  • Telomeric 22q13 Monosomy Syndrome