The Double Bubble Sign: Duodenal Atresia and Associated Genetic Etiologies

Fetal Diagn Ther. 2020;47(2):98-103. doi: 10.1159/000500471. Epub 2019 Jun 5.


Background: The "double bubble" sign is an ultrasonographic finding that commonly represents duodenal atresia and is associated with trisomy 21.

Objectives: We sought to evaluate the positive predictive value of a prenatally identified double bubble sign for duodenal atresia and the genetic etiologies associated with it.

Methods: We examined a retrospective cohort with prenatal double bubble sign between January 1, 2008, and June 30, 2017. Postnatal diagnoses were determined by review of operative reports and additional postnatal evaluation including cytogenetic analysis, molecular analysis, and/or clinical genetic evaluation.

Results: All live births at our institution with a prenatal double bubble sign had confirmed duodenal atresia. Additional anatomic anomalies and/or genetic abnormalities were identified in 62% of cases. Out of 21 cases, 6 had trisomy 21. Of the remaining 15 cases, 8 were nonisolated duodenal atresia, 3 of which had a heterotaxy syndrome. In the 7 isolated cases, 1 likely pathogenic chromosomal microdeletion was identified.

Conclusions: Prenatal double bubble sign is a reliable predictor of duodenal atresia. In addition to trisomy 21, heterotaxy may be encountered. ZIC3 mutations as well as microdeletion of 4q22.3 may be underlying genetic etiologies to be considered in the diagnostic evaluation of a prenatal double bubble sign.

Keywords: Double bubble sign; Duodenal atresia; Prenatal diagnosis.

MeSH terms

  • Chromosome Deletion
  • Chromosomes, Human, Pair 4
  • Down Syndrome / genetics
  • Duodenal Obstruction / diagnostic imaging*
  • Duodenal Obstruction / genetics
  • Genetic Predisposition to Disease
  • Gestational Age
  • Heterotaxy Syndrome / genetics
  • Humans
  • Intestinal Atresia / diagnostic imaging*
  • Intestinal Atresia / genetics
  • Predictive Value of Tests
  • Retrospective Studies
  • Risk Factors
  • Ultrasonography, Prenatal*

Supplementary concepts

  • Familial duodenal atresia