Congenital abnormalities in children with acute leukemia: a report from the Children's Cancer Group

J Pediatr. 1998 Nov;133(5):617-23. doi: 10.1016/s0022-3476(98)70100-3.


Objective: To evaluate the risk of leukemia associated with congenital abnormalities, a series of matched case-control studies were carried out by the Children's Cancer Group.

Study design: Eligible case patients for this analysis included individuals with a diagnosis of leukemia confirmed at a Children's Cancer Group member institution: 2117 diagnosed with acute lymphoblastic leukemia (ALL) and 605 diagnosed with acute myelogenous leukemia (AML). Case patients were compared with matched regional population control subjects selected by using a modified random digit dialing method. Data regarding congenital abnormalities in index children and their siblings were collected by telephone interview with the biologic mother. Relative risk was estimated by using the odds ratio (OR).

Results: More congenital abnormalities were reported in index case patients with ALL than in control subjects, with statistically significant increases in multiple birthmarks (OR = 1.35), Down syndrome (OR = 4.85), congenital heart defects (OR = 1.48), and pancreas-digestive tract abnormalities (OR = 2.52). Similarly, birth defects were reported more often among index case patients with AML than control subjects (OR = 2.90), with significant increases in multiple birthmarks (OR = 1.89), Down syndrome (OR = 76.80), mental retardation (OR = 14.47), and congenital heart defects (OR = 2.07). Exclusion of case patients with Down syndrome from the analysis did not change the statistically significant excess of pancreas-digestive tract abnormalities in case patients with ALL or the excess of multiple birthmarks observed in both case patients with ALL and those with AML. For both the ALL and AML analyses, no significant differences in the number of reported congenital abnormalities were seen between siblings of case patients and siblings of control subjects.

Conclusion: Many of the observed associations with congenital abnormalities occurred in the children with Down syndrome, who are known to have an increased risk for leukemia. The higher reported frequency of birthmarks among case patients may suggest a genetic component to leukemia risk.

Publication types

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

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Congenital Abnormalities / diagnosis
  • Congenital Abnormalities / genetics*
  • Down Syndrome / diagnosis
  • Down Syndrome / genetics
  • Female
  • Genetic Predisposition to Disease / genetics
  • Humans
  • Infant
  • Leukemia, Myeloid, Acute / diagnosis
  • Leukemia, Myeloid, Acute / genetics*
  • Male
  • Odds Ratio
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / diagnosis
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Risk