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

Am J Med Genet C Semin Med Genet. 2019 Dec;181(4):591-610. doi: 10.1002/ajmg.c.31743. Epub 2019 Oct 14.


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.

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

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Age of Onset
  • Child
  • Genetic Predisposition to Disease
  • Genetic Testing
  • Genotype
  • Hamartoma Syndrome, Multiple / diagnosis
  • Hamartoma Syndrome, Multiple / genetics
  • Hamartoma Syndrome, Multiple / physiopathology*
  • Humans
  • Phenotype