Considering the Embryopathogenesis of VACTERL Association

Abstract

The nonrandom co-occurrence of vertebral, anorectal, cardiac, tracheoesophageal, genitourinary, and limb malformations, recognized as the VACTERL association, has not been satisfactorily explained from either a causation or embryopathogenesis standpoint. Few familial cases have been identified and maternal diabetes is the only environmental influence implicated to date. Mutations in single genes have been found in a number of syndromes with one or more of the VACTERL malformations, but these syndromes usually have other features which distinguish them from the VACTERL association. Animal models have provided clues to molecular pathways that may be involved in the embryogenesis of the VACTERL structures. What is lacking is the systematic study of individual genes and pathways in well-composed cohorts of patients, which is now possible with high throughput molecular technologies.

Keywords: Embryology; Embryopathogenesis; Environmental influences; Genetics; Malformations; VACTERL association.

Fig. 1

Approximate days post conception during which anatomic structures in VACTERL association are formed. Genetic or environmental influences that affect the anlage of these structures may occur earlier than the days indicated.

Fig. 2

Thirty-four week female fetus with VACTERL association: 14 thoracic vertebrae and ribs with multiple vertebral segmentation defects at C6–7, T5–6, and T6–7; ectopic hypoplastic anus at base of vagina; cardiomegaly with 2 atrial septal defects, a preductal coarctation (C) and aberrant major branches of aorta in order of right carotid (RC), left carotid (LC), left subclavian (LS), and right subclavian (RS) which coursed behind the esophagus and trachea; tracheoesophageal fistula and esophageal atresia; left renal agenesis and right hydronephrosis; and right radial aplasia with hypoplastic thumb.