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Am J Med Genet C Semin Med Genet. 2019 Oct 14. doi: 10.1002/ajmg.c.31743. [Epub ahead of print]

PTEN Hamartoma tumor syndrome in childhood: A review of the clinical literature.

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Wessex Clinical Genetics Service, University Hospitals Southampton NHS Trust, Southampton, United Kingdom.
Department of Clinical Genetics, East Anglian Medical Genetics Service, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom.
Department of Medical Genetics, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom.
Human Genetics and Genomic Medicine, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.


PTEN hamartoma tumor syndrome (PHTS) is a highly variable autosomal dominant condition associated with intellectual disability, overgrowth, and tumor predisposition phenotypes, which often overlap. PHTS incorporates a number of historical clinical presentations including Bannayan-Riley-Ruvalcaba syndrome, Cowden syndrome, and a macrocephaly-autism/developmental delay syndrome. Many reviews in the literature focus on PHTS as an adult hamartoma and malignancy predisposition condition. Here, we review the current literature with a focus on pediatric presentations. The review starts with a summary of the main conditions encompassed within PHTS. We then discuss PHTS diagnostic criteria, and clinical features. We briefly address rarer PTEN associations, and the possible role of mTOR inhibitors in treatment. We acknowledge the limited understanding of the natural history of childhood-onset PHTS as a cancer predisposition syndrome and present a summary of important management considerations.


Bannayan-Riley-Ruvalcaba syndrome; PHTS; PTEN hamartoma tumor syndrome; autism spectrum disorder; cowden syndrome


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