Table 2 Reported causes of features seen in VACTERL association in human patients.

Mitochondrial dysfunction

Patients typically have clinical features consistent with mitochondrial dysfunction (though these may not be apparent until long after the malformations associated with VACTERL association have been discovered)

[77–81]

Pathogenic copy number variations

Many different deletions/duplications have been reported*, though the evidence for causation of VACTERL association-type features is not uniformly clear. Clinical features in patients with large genomic imbalances often include malformations and medical issues not commonly seen in VACTERL association (such as neurocognitive impairment)

[82–86]

Heterozygous mutations in HOXD13

Described in one patient; mutations in HOXD13 are more typically reported as resulting in limb and/or urogenital anomalies

[51, 87, 88]

Heterozygous/

hemizygous mutations in ZIC3

Clinical features may or may not include obvious heterotaxy/situs abnormalitites

[89–91]