PTEN, DICER1, FH, and Their Associated Tumor Susceptibility Syndromes: Clinical Features, Genetics, and Surveillance Recommendations in Childhood

Clin Cancer Res. 2017 Jun 15;23(12):e76-e82. doi: 10.1158/1078-0432.CCR-17-0629.


PTEN hamartoma tumor syndrome (PHTS), DICER1 syndrome, and hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome are pleiotropic tumor predisposition syndromes that include benign and malignant neoplasms affecting adults and children. PHTS includes several disorders with shared and distinct clinical features. These are associated with elevated lifetime risk of breast, thyroid, endometrial, colorectal, and renal cancers as well as melanoma. Thyroid cancer represents the predominant cancer risk under age 20 years. DICER1 syndrome includes risk for pleuropulmonary blastoma, cystic nephroma, ovarian sex cord-stromal tumors, and multinodular goiter and thyroid carcinoma as well as brain tumors including pineoblastoma and pituitary blastoma. Individuals with HLRCC may develop multiple cutaneous and uterine leiomyomas, and they have an elevated risk of renal cell carcinoma. For each of these syndromes, a summary of the key syndromic features is provided, the underlying genetic events are discussed, and specific screening is recommended. Clin Cancer Res; 23(12); e76-e82. ©2017 AACRSee all articles in the online-only CCR Pediatric Oncology Series.

Publication types

  • Review

MeSH terms

  • Child
  • DEAD-box RNA Helicases / genetics*
  • Early Detection of Cancer
  • Fumarate Hydratase / genetics*
  • Hamartoma Syndrome, Multiple / epidemiology
  • Hamartoma Syndrome, Multiple / genetics*
  • Hamartoma Syndrome, Multiple / pathology
  • Humans
  • Leiomyomatosis / epidemiology
  • Leiomyomatosis / genetics*
  • Leiomyomatosis / pathology
  • Neoplastic Syndromes, Hereditary / epidemiology
  • Neoplastic Syndromes, Hereditary / genetics*
  • Neoplastic Syndromes, Hereditary / pathology
  • PTEN Phosphohydrolase / genetics*
  • Ribonuclease III / genetics*
  • Risk Factors
  • Skin Neoplasms / epidemiology
  • Skin Neoplasms / genetics*
  • Skin Neoplasms / pathology
  • Uterine Neoplasms / epidemiology
  • Uterine Neoplasms / genetics*
  • Uterine Neoplasms / pathology


  • DICER1 protein, human
  • Ribonuclease III
  • PTEN Phosphohydrolase
  • PTEN protein, human
  • DEAD-box RNA Helicases
  • Fumarate Hydratase

Supplementary concepts

  • Hereditary leiomyomatosis and renal cell cancer