Is gastroschisis truly a sporadic defect?: familial cases of gastroschisis in Utah, 1997 to 2008

Birth Defects Res A Clin Mol Teratol. 2011 Oct;91(10):873-8. doi: 10.1002/bdra.22844. Epub 2011 Aug 24.


Background: Gastroschisis remains an epidemiologic and pathogenetic dilemma, with genetics not thought to play a significant role in its etiology. The purpose of this study was to determine which gastroschisis cases in the Utah Birth Defect Network (UBDN) were related and the excess familial risk among multigenerational families.

Methods: Gastroschisis cases born from 1997 through 2008 were identified from the statewide population-based UBDN and linked with the Utah Population Database (UPDB) to access multigenerational pedigrees. We analyzed these pedigrees using the familial standardized incidence ratio (FSIR).

Results: Of the 284 UBDN gastroschisis cases, one in 40 (n = 7; 2.5%) were reported to have another affected family member. Among these seven cases, three had affected sib pairs and four reported either a distant cousin, paternal uncle, maternal half-uncle, or paternal cousin with gastroschisis. UBDN-UPDB-linked cases resulted in many multigenerational pedigrees with the same affected descendents through marriage. We selected 30 pedigrees for repeated analysis based on two parameters: highest FSIRs with a p ≤ 0.01 and ≥2 cases. In these 30 pedigrees, FSIRs ranged from 3.7 to 93.5 (p < 0.009), each with two to eight distantly related cases (n = 64 distinct cases, representing 23% of the 284).

Conclusions: We found a statistically significant excess risk for gastroschisis because of familial factors. Similar to many other birth defects, gastroschisis may fit a multifactorial model of inheritance. The UBDN-UPDB linkage provides a robust approach to investigating genetic factors. Genetic susceptibility should be further investigated because it may have a greater role in the etiology of gastroschisis than currently appreciated.

Publication types

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

MeSH terms

  • Databases, Factual*
  • Family
  • Female
  • Gastroschisis / epidemiology
  • Gastroschisis / genetics*
  • Humans
  • Male
  • Multifactorial Inheritance / genetics*
  • Pedigree*
  • Retrospective Studies
  • Utah / epidemiology