VACTERL association is usually defined by the presence of at least three of the following congenital anomalies involving different organ systems: Vertebral defects, Anal atresia, Cardiac defects, Tracheo-Esophageal fistula, Renal anomalies, and Limb abnormalities.
VACTREL (VATER sybdrome, Holt Oram Syndrome)
Abstract: VACTERL association is usually defined by the presence of at least three of the following congenital anomalies involving different organ systems: Vertebral defects, Anal atresia, Cardiac defects, Tracheo-Esophageal fistula, Renal anomalies, and Limb abnormalities. VACTERL is not a syndrome, but rather a series of abnormalities in the embryological development leading to distinct multi-system anomalies. The majority of VACTERL cases appear to be sporadic events, with unknown etiology. The condition is established clinically when the abnormalities above are detected on prenatal ultrasound, following exclusion of other genetic conditions with overlapping features (but not limited to), such as X-linked VACTERL with hydrocephalus, CHARGE syndrome, Fanconi anaemia, Holt-Oram syndrome, Townes-Brocks syndrome and Trisomy 18. The management of VACTERL focuses on the surgical interventions in the postnatal period. The prognosis of VACTERL is determined by the number, severity and nature of abnormalities present.
Key Words: VACTERL association, VATER association, VACTREL
Authors: Delima Khairudin1, Asma Khalil1,2,3
- Fetal Medicine Unit, Liverpool Women’s NHS Foundation Trust, Liverpool, UK
- Fetal Medicine Unit, St George's University Hospitals NHS Foundation Trust, UK
- Vascular Biology Research Centre, Molecular and Clinical Sciences Research Institute, St George's University of London, London, UK
Reviewer: Karen Fung-Kee-Fung
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This article should be cited as: Khairudin D, Khalil A: VACTERL association, Visual Encyclopedia of Ultrasound in Obstetric and Gynecology, www.isuog.org, May 2022.
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Definition
VACTERL association is usually defined by the presence of at least three of the following congenital anomalies involving different organ systems: Vertebral defects, Anorectal malformation (ARM), Cardiac defects, Tracheo-Esophageal fistula (TEF), Renal anomalies, and Limb abnormalities. At present, there is no universally accepted standardised diagnostic criteria with regards to which features should be encompassed for its diagnosis (1). The presence of at least three VACTERL features are routinely utilised by most clinicians and researchers for diagnosis, although some would emphasise or require the presence of specific core features such as ARM and TEF (2).
ICD code
Q87.2
Incidence
VACTERL occurs in approximately 1 in 10,000 to 1:40,000 newborns (3). The prevalence of VACTERL was 1 in 20,000 births in 2012–2016 according to the EUROCAT (European Surveillance of Congenital Anomalies) central database (4).
Etiology
The etiology is unknown, with most cases occurring sporadically. Familial clustering has been reported in a small proportion of cases suggestive of genetic factors (1, 3).
Recurrence risk
The recurrence risk is relatively low when similar conditions with genetic causes are excluded (refer to differential diagnosis) (3).
Diagnosis
Diagnosis of VACTERL association is made clinically, based on the presence of the component features outlined below (4, 5):
|
Component |
Description/prenatal findings (non-exhaustive) |
|
Vertebral |
Scoliosis including hemivertebrae, fusion, or failure of segmentation with scoliosis Rib anomalies Spina bifida, tethered spinal cord |
|
Anorectal |
Absence, atresia, and stenosis of rectum/anus with or without fistula Complex cloacal malformation |
|
Cardiac |
Malformations of the cardiac chambers, septum, valves, the great arteries Isomerism of atrial appendages |
|
Tracheoesophageal Atresia |
Esophageal atresia with or without TEF, TEF with or without atresia |
|
Renal |
Renal agenesis, cystic/dysplastic kidney Lobulated, fused, and horseshoe kidney Obstructive defects of renal pelvis and malformations of ureter |
|
Limb/Radial |
Accessory thumb(s), absence of hand and finger(s) Limb reduction defect Webbed fingers, fused fingers, polysyndactyly |
Differential diagnosis
The differential diagnosis of VACTERL association is vast, comprising of various conditions with multiple common features with VATERL association, but for which genetic testing is available (3):
|
Conditions |
Common features with VACTERL association |
Cause(s) |
|
CHARGE syndrome |
Cardiac defect, genitourinary anomalies; may also include TEF |
Heterozygous mutations in CHD7 |
|
22q11.2 deletion syndrome |
Cardiac defects, renal anomalies, other VACTERL-type anomalies also reported |
Microdeletion of one copy of chromosome 22q11.2 |
|
Fanconi anaemia |
All features of VACTERL association may be present; radial anomalies are considered as a key feature |
Recessive or X-linked mutations in multiple genes |
|
Holt-Oram syndrome |
Cardiac defects, limb malformations |
Heterozygous mutations in TBX5 |
|
Townes-Brocks syndrome |
Imperforate anus, thumb anomalies, renal anomalies, cardiac defects |
Heterozygous mutations in SALL1 |
|
VACTERL-H (hydrocephalus) |
All core component features with hydrocephalus |
Heterozygous mutations in PTEN, heterozygous/ hemizygous mutations in ZIC3 |
Implications for sonographic diagnosis
Care should be taken to systematically assess all the organ systems applicable to VACTERL association when an isolated anomaly is detected.
Prognosis
The prognosis of VACTERL is determined by the number, severity and nature of abnormalities present.
Management
The multiple anomalies detected raising the suspicion of VACTERL association should prompt the discussion surrounding genetic investigations by CVS or amniocentesis, depending on the gestation of pregnancy. Genetic counselling and extended genetic investigations (whole-exome sequencing) should be offered, taking into account the presence of associated anomalies; primarily to exclude conditions with similar presentations but with potential genetic causes.
Termination of pregnancy may be offered especially in cases where major structural anomalies are confirmed in early gestation. For patients opting to continue the pregnancy, ultrasound scan follow up every 4 weeks is recommended for serial growth assessment and re-evaluation of the anomalies, with involvement of the paediatric surgeons and neonatal team.
Delivery in a tertiary unit is recommended and should be planned around 38 weeks’ gestation. Mode of delivery will depend on the severity of the anomalies detected and obstetric indications for Caesarean section.
References
1. Solomon BD. The etiology of VACTERL association: Current knowledge and hypotheses. Am J Med Genet C Semin Med Genet. 2018;178(4):440-6.
2. Solomon BD, Bear KA, Kimonis V, de Klein A, Scott DA, Shaw-Smith C, et al. Clinical geneticists' views of VACTERL/VATER association. Am J Med Genet A. 2012;158A(12):3087-100.
3. Solomon BD. VACTERL/VATER Association. Orphanet J Rare Dis. 2011;6:56.
4. van de Putte R, van Rooij I, Marcelis CLM, Guo M, Brunner HG, Addor MC, et al. Spectrum of congenital anomalies among VACTERL cases: a EUROCAT population-based study. Pediatr Res. 2020;87(3):541-9.
5. Solomon BD, Baker LA, Bear KA, Cunningham BK, Giampietro PF, Hadigan C, et al. An approach to the identification of anomalies and etiologies in neonates with identified or suspected VACTERL (vertebral defects, anal atresia, tracheo-esophageal fistula with esophageal atresia, cardiac anomalies, renal anomalies, and limb anomalies) association. J Pediatr. 2014;164(3):451-7 e1.
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