VACTERL association

**Definition/Components (VACTERL):** - **V**ertebral anomalies (hemivertebrae, butterfly vertebrae, scoliosis) - **A**nal atresia / imperforate anus - **C**ardiac defects (VSD most common; also ASD, TOF, others) - **T**racheo**E**sophageal fistula (with or without esophageal atresia; most commonly type C: proximal atresia with distal fistula) - **R**enal anomalies (renal agenesis, horseshoe kidney, dysplasia, hydronephrosis, vesicoureteral reflux) - **L**imb anomalies (radial ray defects, absent/hypoplastic thumb, polydactyly, radial dysplasia) (Some use VACTERL-H when hydrocephalus is present.)

**Diagnosis:** Clinical diagnosis of exclusion, generally requiring ≥3 of the features. Must rule out overlapping conditions with similar findings.

**Pathophysiology:** Etiology is largely unknown and heterogeneous. It is thought to reflect a defect in early embryonic development (around weeks 4-6 of gestation) affecting mesodermal derivatives and midline structures. It is mostly sporadic, with low recurrence risk. Associated with maternal pregestational diabetes. Some cases have been linked to mitochondrial and sonic hedgehog (SHH) pathway abnormalities. Because it is an "association" and not a syndrome, there is no single identified cause or consistent genetic pattern.

**Clinical significance:** - Neonate may present with polyhydramnios prenatally, excessive drooling, choking, coughing, and cyanosis with feeds (TE fistula), abdominal distention and absent meconium passage (anal atresia), respiratory distress, or a murmur. - Intelligence is typically normal (contrast with chromosomal syndromes). - Management is surgical correction of life-threatening anomalies (TEF repair, anal atresia repair/colostomy, cardiac surgery), with multispecialty follow-up.

**Workup in suspected cases:** Echocardiogram, renal ultrasound, spinal imaging (X-ray/ultrasound/MRI, including for tethered cord), limb X-rays, and an attempt to pass an orogastric tube (it coils in the esophageal pouch if there is atresia). Check also for single umbilical artery.

**Key differential diagnoses (high-yield "mimics"):** - **CHARGE syndrome** (Coloboma, Heart defects, Atresia choanae, Retarded growth/development, Genital anomalies, Ear anomalies; CHD7 mutation) - **Fanconi anemia** (radial ray defects, pancytopenia; DNA repair defect, chromosome breakage test) - **Holt-Oram syndrome** (upper limb/radial defects with cardiac defects, esp. ASD; TBX5) - **Townes-Brocks syndrome** (anal, renal, limb, ear anomalies; SALL1) - **Feingold syndrome** (esophageal/duodenal atresia, microcephaly; MYCN) - **Trisomy 18** and **22q11 deletion (DiGeorge)** - **Currarino syndrome**, **Pallister-Hall**, and **Baller-Gerold** These are tested because Fanconi anemia, in particular, has a serious hematologic implication.

**Board pearls:** - VSD is the most common cardiac lesion in VACTERL. - Single umbilical artery is frequently seen. - Pregestational maternal diabetes is a recognized risk factor. - Think VACTERL in a newborn with TE fistula who also has anal atresia or vertebral anomalies, and look for the other components. - An infant with a radial ray defect plus other anomalies should be evaluated for Fanconi anemia (chromosome breakage testing).