Behavioural and psychological features of PTEN mutations: a systematic review of the literature and meta-analysis of the prevalence of autism spectrum disorder characteristics

Katherine Cummings, Alice Watkins, Chris Jones, Renuka Dias, Alice Welham

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BACKGROUND: Phosphatase and tensin homologue (PTEN) is a cancer suppressor gene. Constitutional mutations affecting this gene are associated with several conditions, collectively termed PTEN hamartoma tumour syndromes (PHTS). In addition to hamartomas, PTEN aberrations have been associated with a range of non-tumoural phenotypes such as macrocephaly, and research indicates possibly increased rates of developmental delay and autism spectrum disorder (ASD) for people with germline mutations affecting PTEN.

METHOD: A systematic review of literature reporting behavioural and psychological variables for people with constitutional PTEN mutations/PHTS was conducted using four databases. Following in-depth screening, 25 articles met the inclusion criteria and were used in the review. Fourteen papers reported the proportion of people with PTEN mutations/PTHS meeting criteria for or having characteristics of ASD and were thus used in a pooled prevalence meta-analysis.

RESULTS: Meta-analysis using a random effects model estimated pooled prevalence of ASD characteristics at 25% (95% CI 16-33%), although this should be interpreted cautiously due to possible biases in existing literature. Intellectual disability and developmental delay (global, motor and speech and language) were also reported frequently. Emotional difficulties and impaired cognitive functioning in specific domains were noted but assessed/reported less frequently. Methods of assessment of psychological/behavioural factors varied widely (with retrospective examination of medical records common).

CONCLUSIONS: Existing research suggests approximately 25% of people with constitutional PTEN mutations may meet criteria for or have characteristics of ASD. Studies have also begun to establish a range of possible cognitive impairments in affected individuals, especially when ASD is also reported. However, further large-scale studies are needed to elucidate psychological/behavioural corollaries of this mutation, and how they may relate to physiological/physical characteristics.

Original languageEnglish
Article number1
JournalJournal of Neurodevelopmental Disorders
Issue number1
Publication statusPublished - 4 Jan 2022

Bibliographical note

© 2021. The Author(s).


  • Autism spectrum disorder
  • Behaviour
  • Cognition
  • Development
  • Emotional difficulties
  • PTEN
  • PTEN hamartoma tumour syndrome

ASJC Scopus subject areas

  • Clinical Neurology
  • Cognitive Neuroscience
  • Pediatrics, Perinatology, and Child Health
  • Pathology and Forensic Medicine


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