Vacterl association is a non-random grouping of birth defects that includes vertebral anomalies, anal atresia, cardiac defects, tracheo-esophageal fistula with or without esophageal atresia, and renal and limb abnormalities. It is considered an association because the defects do not have a predictable pattern and the underlying etiology is unknown. Proposed causes include abnormal segmentation of the vertebrae, effects of teratogenic agents, malformation sequences initiated by vertebral defects, and disturbances in fundamental embryological processes of mesoderm development and migration. Diagnosis requires at least three components of the association to be present.

1. Vacterl Association
Madiha Ali

2. Objective
• To understand Vacterl Association in
relation to etiology, pathogenesis and
diagnosis

3. Introduction
• A syndrome is generally recognized and
defined as a well-characterized constellation
of major and minor anomalies that occur
together in a predictable fashion
presumably due to a single underlying
etiology which may be monogenic,
chromosomal, mitochondrial, or teratogenic in
origin.
• e.g. Down’s Syndrome

4. • A sequence is a group of related anomalies
that generally stem from a single initial
major anomaly that alters the development
of other surrounding or related tissues or
structures.
e.g. Potter’s sequence

5. • An association is a group of anomalies that
occur more frequently together than would
be expected by chance alone but that do not
have a predictable pattern of recognition
and/or a suspected unified underlying etiology.

7. Vertebral

8. Anal

9. Cardiac

10. Tracheoesophageal

11. Renal (genitourinary)

12. Limb

13. 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.

14. Etiopathogenesis

15. Theories
• Abnormal or asymmetric timing of a molecular
oscillator termed the segmentation clock has
been shown to result in malsegmentation of the
vertebrae [Pourquié and Kusumi, 2001; Oates
et al., 2012].

16. • Environmental agents such as Thalidomide (in
humans) [Knapp et al., 1962; Quibell, 1981;
Lenz, 1988] and Adriamycin (inrats) [Beasley
et al., 2000] can produce malformations
similar to VACTERL.

17. Malformation Sequences and
VACTERL Association
• A sequence could be initiated by Vertebral
malsegmentation with secondary malformative
consequences on adjacent (tracheoesophageal,
cardiac, and renal) structures and remote (limb
and anal) structures. The secondary
consequences might involve vascular
disturbance(s) as an intermediary phenomenon

18. Disturbance in a Developmental Process and
VACTERL Association
• Adequate mesoderm production must occur
via migration and transformation of precursor
ectoderm through the primitive streak,
proliferation, and distribution to all sites of
embryogenesis. Disturbance of this
fundamental embryological process plausibly
might disrupt development globally, leading to
embryonic death or locally producing faulty
formation of individual anatomical structures.

19. Genetic pathways
• Sonic hedge hog
• NOTCH
• Fibroblast growth factor (FGF)

20. Diagnostic approaches
• Atleast three components
• Presence of certain component features such as
EA and ARM
• Spatially disparate (occuring on both above
and below diaphragm) precence of anomalies

21. References
• Solomon B D: VACTERL/VATER
Association. Orphanet Journal of Rare
Diseases 2011; 6:56.
• Stevenson R E, Hunter A.G.W: Considering
the Embryopathogenesis of VACTERL
Association. Mol Syndromol 2013;4:7–15

22. Thank you