Recommendations for Cancer Surveillance in Individuals with RASopathies and Other Rare Genetic Conditions with Increased Cancer Risk

Clin Cancer Res. 2017 Jun 15;23(12):e83-e90. doi: 10.1158/1078-0432.CCR-17-0631.

Abstract

In October 2016, the American Association for Cancer Research held a meeting of international childhood cancer predisposition syndrome experts to evaluate the current knowledge of these syndromes and to propose consensus surveillance recommendations. Herein, we summarize clinical and genetic aspects of RASopathies and Sotos, Weaver, Rubinstein-Taybi, Schinzel-Giedion, and NKX2-1 syndromes as well as specific metabolic disorders known to be associated with increased childhood cancer risk. In addition, the expert panel reviewed whether sufficient data exist to make a recommendation that all patients with these disorders be offered cancer surveillance. For all syndromes, the panel recommends increased awareness and prompt assessment of clinical symptoms. Patients with Costello syndrome have the highest cancer risk, and cancer surveillance should be considered. Regular physical examinations and complete blood counts can be performed in infants with Noonan syndrome if specific PTPN11 or KRAS mutations are present, and in patients with CBL syndrome. Also, the high brain tumor risk in patients with L-2 hydroxyglutaric aciduria may warrant regular screening with brain MRIs. For most syndromes, surveillance may be needed for nonmalignant health problems. Clin Cancer Res; 23(12); e83-e90. ©2017 AACRSee all articles in the online-only CCR Pediatric Oncology Series.

Publication types

  • Review

MeSH terms

  • Abnormalities, Multiple / epidemiology*
  • Abnormalities, Multiple / genetics
  • Abnormalities, Multiple / pathology
  • Brain Neoplasms / epidemiology
  • Brain Neoplasms / genetics
  • Brain Neoplasms / pathology
  • Colorectal Neoplasms / epidemiology
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / pathology
  • Congenital Hypothyroidism / epidemiology*
  • Congenital Hypothyroidism / genetics
  • Congenital Hypothyroidism / pathology
  • Costello Syndrome / epidemiology
  • Costello Syndrome / genetics
  • Costello Syndrome / pathology
  • Craniofacial Abnormalities / epidemiology*
  • Craniofacial Abnormalities / genetics
  • Craniofacial Abnormalities / pathology
  • Hand Deformities, Congenital / epidemiology*
  • Hand Deformities, Congenital / genetics
  • Hand Deformities, Congenital / pathology
  • Humans
  • Intellectual Disability / epidemiology*
  • Intellectual Disability / genetics
  • Intellectual Disability / pathology
  • Mutation
  • Nails, Malformed / epidemiology*
  • Nails, Malformed / genetics
  • Nails, Malformed / pathology
  • Neoplastic Syndromes, Hereditary / epidemiology
  • Neoplastic Syndromes, Hereditary / genetics
  • Neoplastic Syndromes, Hereditary / pathology
  • Noonan Syndrome / epidemiology
  • Noonan Syndrome / genetics
  • Noonan Syndrome / pathology
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11 / genetics
  • Risk Factors
  • Rubinstein-Taybi Syndrome / epidemiology*
  • Rubinstein-Taybi Syndrome / genetics
  • Rubinstein-Taybi Syndrome / pathology
  • Sotos Syndrome / epidemiology*
  • Sotos Syndrome / genetics
  • Sotos Syndrome / pathology
  • Thyroid Nuclear Factor 1 / genetics

Substances

  • NKX2-1 protein, human
  • Thyroid Nuclear Factor 1
  • PTPN11 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11

Supplementary concepts

  • Schinzel-Giedion syndrome
  • Turcot syndrome
  • Weaver syndrome