High incidence of malformation syndromes in a series of 1,073 children with cancer

Am J Med Genet A. 2005 Apr 15;134A(2):132-43. doi: 10.1002/ajmg.a.30603.


Constitutional molecular defects are known to play a role in oncogenesis, as shown by the increased incidence of embryonic cancers in children with Beckwith-Wiedemann syndrome (BWS) or of leukemia in children with Down syndrome. To establish the incidence and spectrum of malformation syndromes associated with childhood cancer we performed a clinical morphological examination on a series of 1,073 children with cancer. We diagnosed a syndrome in 42 patients (3.9%) and suspected the presence of a syndrome in another 35 patients (3.3%), for a total of 7.2%. This incidence of patients with a proven or suspected syndrome is high, and points to a possible association. We describe new syndrome-tumor associations in several entities: cleidocranial dysostosis (Wilms tumor), Bardet-Biedl syndrome (BBS) (acute lymphoblastic leukemia), Kabuki syndrome (neuroblastoma), LEOPARD syndrome (neuroblastoma), Poland anomaly (osteosarcoma; Hodgkin disease), and blepharophimosis epicanthus inversus syndrome (Burkitt lymphoma). Twenty of the 42 syndrome diagnoses were not recognized in the patients prior to this study, indicating that these diagnoses are commonly missed. We propose that all children with a malignancy should be examined by a clinical geneticist or a pediatrician skilled in clinical morphology to determine if the patients have a malformation syndrome.

MeSH terms

  • Abnormalities, Multiple / diagnosis
  • Abnormalities, Multiple / epidemiology*
  • Abnormalities, Multiple / genetics
  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Cohort Studies
  • Comorbidity
  • DNA Methylation
  • Female
  • Genetic Predisposition to Disease / genetics
  • Humans
  • Incidence
  • Infant
  • Infant, Newborn
  • Male
  • Middle Aged
  • Mutation
  • Neoplasms / epidemiology*
  • Netherlands / epidemiology
  • Syndrome