Epidemiology and Genetics
- Incidence: 1 in 10,000–40,000 live births
- Recurrence risk in a sibling or child: < 1%
- VACTERL cases are often sporadic.
- Often no family history of condition
- No clear inheritance pattern
- Multiple genetic and environmental factors likely contribute, but specifics are unknown.
The acronym VACTERL describes the clinical manifestations of the condition.
- V for Vertebral abnormalities
- Misshapen, fused, missing, or extra vertebrae present
- Scoliosis secondary to underlying vertebral anomalies
- A for Anal atresia (imperforate anus)
- Complete or partial/stenosis
- Bowel obstruction/inability to pass meconium
- C for Cardiac defects
- Ventricular septal defect (VSD) is the most common
- Less commonly, atrial septal defect (ASD) or tetralogy of Fallot
- T for Tracheoesophageal fistula
- Abnormal connection between the trachea and esophagus
- Causes breathing and feeding difficulties
- E for Esophageal atresia (duodenal atresia may also be seen)
- R for Renal anomalies
- Horseshoe kidney, unilateral/bilateral renal agenesis (missing kidney), cystic/dysplastic kidneys
- May affect kidney function
- L for Limb abnormalities
- Thumb aplasia/hypoplasia (underdeveloped or missing thumbs)
- Radial dysplasia (underdeveloped or missing radius in forearms)
- Polydactyly, syndactyly
- Single umbilical artery (normally 2)
- Fanconi’s anemia
- Genital and urinary tract abnormalities
- Rib anomalies
- Pulmonary anomalies
- Ear malformations
Diagnosis and Management
VACTERL is a diagnosis of exclusion. All other possible conditions should be evaluated and ruled out.
- History and clinical examination:
- At least three of the defining characteristics needed for diagnosis
- Finding one abnormality in this association should prompt evaluation for others.
- Those with renal or characteristic limb anomalies should undergo genetic screening for Fanconi’s anemia.
- Chest radiograph to evaluate for vertebral, rib, and possible pulmonary anomalies
- Echo to evaluate for cardiac defects
- Renal ultrasound to evaluate for renal anomalies
- Abdominal ultrasound to evaluate for genitourinary anomalies
- Spinal ultrasound and spinal radiographs to evaluate for spinal anomalies
- Limb radiographs to evaluate for radial dysplasia
- Labs/genetic testing not done for diagnosis of VACTERL association, but to evaluate for conditions in the differential diagnosis
- Medical management:
- Nasogastric intubation (feeding tube)
- Surgical management:
- Certain malformations (e.g., anal atresia, tracheoesophageal fistula, and certain cardiac defects) may require surgery in the 1st few days or years of life.
- Additional surgeries may be required later depending on malformations present.
Multiple syndromes have clinical features overlapping with VACTERL association. The presence of anomalies not characteristic of VACTERL association, in combination with genetic testing, can help differentiate most of these syndromes. The following is a selection of the most important differential diagnoses:
- CHARGE syndrome: a rare genetic condition with autosomal dominant inheritance in which almost all body systems are affected. The term CHARGE is an acronym for the clinical features seen with this condition: Coloboma, Heart defects, Atresia choanae, Growth retardation and Genetic abnormalities, and Ear abnormalities. Genetic testing confirms the diagnosis. Treatment is symptomatic, with management of the airway, heart defects, and feeding ability as the priorities in early life.
- Townes-Brocks syndrome: a rare genetic condition with autosomal dominant inheritance. Also affects multiple body systems with similar clinical features as VACTERL association, with the most common features being anal atresia, ear anomalies, and thumb abnormalities. Unlike VACTERL, hearing loss is common with this condition. Tracheoesophageal fistulas and vertebral anomalies are not typically seen. Genetic testing confirms the diagnosis. Early intervention with hearing aids is needed for hearing loss. Additional treatments are based on clinical manifestations.
- Pallister-Hall syndrome: a rare genetic condition with autosomal dominant inheritance. Affects multiple body systems with similar features to VACTERL association. However, a hypothalamic hamartoma is pathognomonic. Additional features include bifid epiglottis, nail hypoplasia, and polydactyly. Genetic testing confirms the diagnosis. Treatment is based on the clinical manifestations present.
- Fanconi’s anemia: genetic condition with autosomal recessive or X-linked inheritance. A multitude of congenital defects similar to that in VACTERL association is present. Renal and characteristic limb anomalies (missing thumb/radius) are particularly seen. Fanconi’s anemia is associated with bone marrow failure, acute myeloid leukemia (AML), and other types of neoplasia. Chromosomal breakage studies help confirm the diagnosis. Treatment involves bone marrow transplant, blood transfusions, medication, and possibly surgery depending on clinical manifestations.
- VACTERL-H: a genetic condition involving all the clinical features of VACTERL association, with the additional finding of hydrocephalus. The condition may have an autosomal recessive or X-linked pattern of inheritance. Diagnosis is clinical and one of exclusion. A shunt may be needed to help drain excess cerebrospinal fluid for treatment of the hydrocephalus. Additional treatments are based on clinical manifestations.
- Solomon B. D. (2011). VACTERL/VATER Association. Orphanet journal of rare diseases, 6, 56. https://doi.org/10.1186/1750-1172-6-56
- VACTERL association. MedlinePlus. Retrieved December 8, 2020. URL: https://medlineplus.gov/genetics/condition/vacterl-association/#causes
- Altera, B. P. & Rosenberg, P.S. (2013). VACTERL-H Association and Fanconi Anemia. Mol Syndromol. 4(1–2): 87–93. doi: 10.1159/000346035
- Bacino, C.A. (2019). Birth defects: Epidemiology, types, and patterns. UpToDate. Retrieved December 8, 2020. URL: https://www.uptodate.com/contents/birth-defects-epidemiology-types-and-patterns?sectionName=Association&search=vacterl&topicRef=6377&anchor=H3788531324&source=see_link#H3282666919
- Yang, L., Li, S., Zhong, L., Qiu, L., Xie, L., & Chen, L. (2019). VACTERL association complicated with multiple airway abnormalities: A case report. Medicine, 98(42), e17413. https://doi.org/10.1097/MD.0000000000017413