Cause and symptoms
Diagnosis and treatment
VACTERL association, a multisystem congenital malformation, is a disorder involving several characteristics like vertebral defects, anorectal malformations, cardiac defects, tracheoesophageal fistula, renal anomalies, and limb abnormalities.
At least three of these characteristics are common among people who have been diagnosed with the VACTERL association. Affected people may have additional abnormalities that aren't associated with the VACTERL association.
In 1972, it was first given the name VATER (without the ‘C’ and ‘L’). Because no major genetic risk factors have been identified and no genetic test is available, VACTERL is diagnosed by ruling out overlapping illnesses that share many of the same symptoms as VACTERL.
VATER, a combination of associated defects was pointed out by Quan and Smith in 1972. Finer et al. (1978) described two male sibs who had many congenital abnormalities, including notable signs of a caudal regression syndrome, that were suggestive of the VATER relationship.
The elder child had several heart problems, including transposition of the major arteries and a ventricular septal defect. Imperforate anus, a deformed sacrum, and hypoplasia of the lumbar vertebrae were among the other symptoms.
The younger sibling suffered hypoplasia of the lower limbs and pelvis, as well as an absence of the sacrum and lower lumbar spine, suggesting a ventricular septal defect or patent ductus arteriosus.
Khoury et al. (1983) studied the interrelationship between the 6 components of the VACTERL association using a birth defects monitoring registry. There were 400 occurrences with two or more of the components.
The most prevalent cardiovascular abnormality (30%) and renal agenesis were the most common renal anomalies (30%) in the remaining 50 cases that were judged to have a VACTERL association.
Causes and symptoms
VACTERL association is a complicated illness that can have a variety of reasons depending on the individual. The disorder is likely caused by a combination of hereditary and environmental factors in some people. Some genetic and environmental effects have been discovered and are being investigated.
The VACTERL association is characterized by developmental problems that begin before birth. The VACTERL association is thought to be caused by a disruption in fetal development that starts early in development, resulting in birth abnormalities that impact various body systems.
It is unclear why the VACTERL association's characteristics cluster together among affected people.
In 60 to 80 percent of patients with the VACTERL association, defects in the vertebrae's bones are prevalent. Misshapen vertebrae, fused vertebrae, and missing or additional vertebrae are examples of these abnormalities.
Spinal disorders in some people necessitate surgery or cause long-term health issues, such as back discomfort of varying degrees. Sixty to ninety percent of people with the VACTERL association experience constriction or occlusion of the anus (anal atresia).
Anal atresia can be accompanied by genital and urinary tract problems (genitourinary anomalies). A tracheoesophageal fistula (TEF) affects 50 to 80 percent of patients with the VACTERL association. Early in life, a tracheoesophageal fistula can cause breathing and feeding problems, and it usually requires surgical correction in infancy.
Congenital heart disease has been documented in up to 75% of patients with the VACTERL association. Ventricular septal defect (VSD), atrial septal defect (ASD), and tetralogy of Fallot are the most frequent cardiac defects associated with the VACTERL gene.
Truncus arteriosus and transposition of the great arteries are less prevalent abnormalities. Although babies may have a murmur at birth, this does not rule out congenital heart disease.
About half of the people with the VACTERL association have renal or kidney abnormalities. Furthermore, up to 35% of patients with VACTERL have a single umbilical artery (typically two), which is frequently related to kidney or urologic issues.
These abnormalities can be severe, resulting in incomplete kidney formation or urologic abnormalities such as restriction of urine outflow from the kidneys or significant urine reflux (backflow) into the kidneys from the bladder. These issues can lead to renal failure early in childhood, necessitating a kidney transplant. Many of these issues can be treated surgically before they cause any harm.
Absent or misplaced thumbs, extra digits (polydactyly), digit fusion (syndactyly), and forearm deformities are also common limb malformations in babies with the VACTERL association. Newborns with limb deformities on both sides of the body are more likely to have kidney or urologic problems on both sides, whereas babies with limb defects on only one side of the body are more likely to have kidney issues on that side.
Many VACTERL newborns are born tiny and have trouble gaining weight. They do, however, have typical growth and intelligence.
There is significant evidence that a proportion of VACTERL has a genetic foundation, although the evidence that all or even most affected patients have a genetic basis is mixed.
The fact that genetic causes continue to be discovered, albeit in a small fraction of patients per reason and per cohort analyzed by researchers, provides evidence for a genetic basis for the disorder.
Other critical developmental pathways (e.g., FGF and NOTCH signaling) have been implicated in VACTERL pathogenesis in addition to Hedgehog signaling, however, a complete understanding of the underlying biology is still lacking.
Clinical-genomic studies on an extremely large scale (global) combined with fundamental biological investigations may be able to elucidate the causes in the future.
There have been varying estimates of the condition's incidence, just as there have been varying estimations of the condition's exact definitions. The incidence has been estimated to be between 1 in 10,000 and 1 in 40,000 babies.
Diagnosis and treatment
Currently, there is no general agreement on which component features should be included in diagnostic criteria, however, most clinicians and researchers require the presence of at least three VACTERL component features for diagnosis.
Certain basic traits, such as anorectal malformations and TEF, are more severely weighted and/or required by some doctors and researchers. The treatment of VACTERL association is performed based on the various symptoms present in the patient. Most defects like spinal disorders are treated through surgeries.
- Solomon BD (2018). The etiology of VACTERL association: Current knowledge and hypotheses. American journal of medical genetics. Part C, Seminars in Medical Genetics, 178(4), 440–446. https://doi.org/10.1002/ajmg.c.31664
- Chen Y, Liu Z, Chen J, et al. (2016). The genetic landscape and clinical implications of vertebral anomalies in VACTERL association. Journal of Medical Genetics, 53(7), 431–437. doi:10.1136/jmedgenet-2015-103554
- Stevenson RE, & Hunter AG (2013). Considering the Embryopathogenesis of VACTERL Association. Molecular Syndromology, 4(1-2), 7–15. doi:10.1159/000346192
- VACTERL association. [Online] Medline Plus. Available at: https://medlineplus.gov/genetics/condition/vacterl-association/
- VATER Syndrome/VACTERL Association. [Online] Cincinnati Children’s. Available at: https://www.cincinnatichildrens.org/health/v/vacterl
- VATER/VACTERL ASSOCIATION. [Online] OMIM. Available at: https://www.omim.org/entry/192350
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Last Updated: Sep 18, 2023