A newborn has a single umbilical artery on routine inspection. Prenatal imaging had shown a missing radius and an "absent stomach bubble." After birth, the infant is unable to feed and a feeding tube cannot pass, indicating esophageal atresia with tracheoesophageal fistula. Echo reveals a VSD; renal ultrasound shows unilateral renal agenesis.
Sporadic in nearly all cases. No single causative gene; thought to be a multifactorial defect of midline mesoderm/endoderm development around the 4th gestational week. Rare familial recurrence suggests genetic heterogeneity (HOXD13, FANCB, mitochondrial mutations in some). Recurrence risk in subsequent pregnancies is generally <5%.
VACTERL is an association, not a syndrome: no unifying mechanism, just statistical co-occurrence of three or more component defects.
Diagnosis requires ≥3 of the following 6 components:
- Vertebral defects: hemivertebrae, butterfly vertebrae, sacral agenesis (~70%)
- Anal atresia (~55%)
- Cardiac defects: VSD most common, also TOF, ASD (~75%)
- Tracheoesophageal fistula with Esophageal atresia (~70%)
- Renal anomalies: agenesis, dysplasia, reflux (~50%)
- Limb anomalies: radial ray defects (absent thumb, hypoplastic radius) (~50%)
Single umbilical artery is a soft marker, not a criterion.
- Clinical (≥3 cardinal components on physical exam + imaging)
- Echocardiogram, renal ultrasound, vertebral imaging, limb radiographs: full workup once one component is identified
- Rule out mimics with chromosomal/genetic testing: karyotype, CMA, FANCB (X-linked), trio exome considered if multiple anomalies are atypical
- Fanconi anemia must be excluded via chromosome breakage study (DEB/MMC); it shares overlapping radial ray, renal, and cardiac findings, but Fanconi adds bone marrow failure and cancer risk
- Fanconi anemia: see above; required to exclude
- CHARGE syndrome: coloboma, choanal atresia, ear anomalies; CHD7
- Townes-Brocks syndrome: anal atresia + ear + radial ray; SALL1
- Feingold syndrome: TEF + microcephaly + brachymesophalangy; MYCN
- 22q11.2 deletion: cardiac defect + characteristic facies + immune findings
- Surgical repair of correctable anomalies (TEF/EA in first days; anal atresia; cardiac repair as indicated)
- Renal replacement if bilateral severe disease
- Spine and limb orthopedic management long-term
- Developmental support: most have normal cognition, but multiple surgeries and chronic illness affect schooling
- Genetic counseling: sporadic, low recurrence; offer prenatal imaging in subsequent pregnancies
The acronym IS the diagnostic checklist: Vertebral, Anal, Cardiac, Tracheoesophageal, Esophageal, Renal, Limb. Three or more = association. Always exclude Fanconi anemia: it shares the radial ray + cardiac + renal phenotype.