Vacterl Association

Madiha Ali

Objective

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

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

• 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

• 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.

Vertebral

Anal

Cardiac

Tracheoesophageal

Renal (genitourinary)

Limb

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 atbase of vagina; cardiomegaly with 2 atrial septal defects, a preductal coarctation (C) and aberrant major branches of aorta in orderof right carotid (RC), left carotid (LC), left subclavian (LS), and right subclavian (RS) which coursed behind the esophagus andtrachea; tracheoesophageal fistula and esophageal atresia; left renal agenesis and right hydronephrosis; and right radial aplasiawith hypoplastic thumb.

Etiopathogenesis

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].

• 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.

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

Disturbance in a Developmental Process andVACTERL 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.

Genetic pathways

• Sonic hedge hog• NOTCH• Fibroblast growth factor (FGF)

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

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

Thank you