Objective It is recognised that 5% – 10 % of children with macrocephaly and autism spectrum disorder (ASD) and/or intellectual disability (ID) have a heterozygous pathogenic mutation in the PTEN tumour suppressor gene that is associated with PTEN hamartoma tumour syndrome. However, the clinical features and course in children with a pathogenic PTEN mutation are unclear and have not been well documented.
Study objectives We undertook a retrospective chart review of children (< 18 years) with pathogenic PTEN mutations to ascertain clinical findings, clinical course and possible outcomes.
Results Clinical and molecular data were collected and analysed for 47 patients with PTEN mutation from 38 eligible families. Macrocephaly (average head circumference of + 5.7 SD) with developmental delay, ID and/or ASD were the most common presenting signs/symptoms (66 %). Clinical features included dermatological findings (66 %), gastrointestinal (GI) symptoms (34 %), ASD diagnosis (50 %), abnormal brain imaging (53 % of those examined) and abnormal thyroid imaging (26 %).
Conclusions This is the largest survey of clinical features in children with PTEN pathogenic mutations to date. It confirms earlier reports of increased rates of neurodevelopmental disorders. Dermatological, GI and thyroid abnormalities are age dependent and may not be present at the time of diagnosis, requiring regular monitoring and medical surveillance. Early paediatric diagnosis is important for institution of medical and developmental surveillance as well as for testing other at- risk family members.
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Contributors All authors have seen and approved the submission of this manuscript, and take full responsibility for the manuscript. All authors critically revised the manuscript and gave final approval.
Competing interests EHK, TP, SB, SE, BA, CE and GH declare relevant no conflicts of interest. TF has received federal funding or research support from, acted as a consultant to, received travel support from and/or received a speaker’s honorarium from the Cole Family Research Fund, Simons Foundation, Ingalls Foundation, Forest Laboratories, Ecoeos, IntegraGen, Kugona LLC, Shire Development, Bristol-Myers Squibb, National Institutes of Health and the Brain and Behavior Research Foundation.
Ethics approval Nationwide Children's Hospital IRB.
Provenance and peer review Not commissioned; externally peer reviewed.
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