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Blastogenetic associations: General considerations.

Mark Lubinsky1

  • 16003 W. Washington Blvd, Wauwatosa, Wisconsin, 53213.

American Journal of Medical Genetics. Part A
|July 16, 2015
PubMed
Summary

Congenital anomaly associations, like VACTERL, may stem from teratologic interactions between environmental disruptions and embryonic vulnerabilities. Timing and location of exposure during early development influence the resulting patterns of birth defects.

Keywords:
VACTERLassociationsblastogenesisdevelopmental fieldslethalitymalformationsmultiple congenital anomalies

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Area of Science:

  • Developmental biology
  • Teratology
  • Medical genetics

Background:

  • The VACTERL association is a prototype for debated congenital anomaly groupings.
  • Existing models struggle to explain the variability and overlap of anomalies within these associations.

Purpose of the Study:

  • To propose a teratologic model for congenital anomaly associations.
  • To explain the origin of variable sequelae based on embryonic development.

Main Methods:

  • Review of evidence supporting a teratologic basis for anomaly associations.
  • Analysis of developmental timing, location, and vulnerability interactions.

Main Results:

  • Embryonic development involves distinct "teratogenetic fields" influenced by timing, location, and severity of disruptive events.
  • These fields can lead to causally nonspecific malformations and variable anomaly combinations.
  • Specific defects can bias the frequency of other anomalies, explaining overlaps.

Conclusions:

  • Congenital anomaly associations may arise from nonspecific teratogenetic fields rather than polytopic developmental fields.
  • This model accounts for the high incidence of multiple anomalies and overlapping features.
  • Vulnerabilities and exposure timing during the blastogenetic stage are key determinants.