What Is Vater Syndrome

Vater syndrome, also known as VACTERL association, is a clinically heterogeneous disorder characterised by variable severity of vertebral, anal, cardiac, tracheal, renal, and limb anomalies. First characterised in 1972, VATER/VACTERL remains poorly understood but is estimated to affect between one in ten thousand and forty thousand infants worldwide.¹ Current evidence suggests that genetic factors interacting with environmental disruptors during embryonic development contribute to the constellation of congenital defects, although the precise cause is unknown.¹ Diagnosis is based on the recognition of the pattern of component features as opposed to a specific confirmatory test. Multiple paediatric subspecialties must collaborate to surgically correct congenital anomalies and provide ongoing medical, developmental, and psychological support.² Despite the availability of treatments, afflicted children frequently suffer from significant morbidity.² This complex association of birth defects requires further study to elucidate the aetiology, refine diagnostic criteria, and enhance long-term outcomes. This article provides an up-to-date summary of the epidemiology, pathogenesis, clinical presentation, diagnosis, treatment, and prognosis of VATER/VACTERL syndrome.

• Vertebral abnormalities
• Anal atresia
• Cardiac abnormalities
• Tracheoesophageal malformation
• Renal abnormalities
• Limb abnormalities

Aetiology

Although the precise causes of VATER association remain unknown, the prevailing theory implicates a genetic and environmental disturbance of early embryonic development. Certain gene mutations have been linked to component features, suggesting a genetic influence,³ despite the fact that the disorder lacks a distinct Mendelian inheritance pattern. Proposed disease-causing variants include mutations in ZIC3, HOXD13, FGF10, and FOXF1, among others. However, the rarity of familial cases suggests that inheritance is complex rather than monogenic.³ The majority of evidence points to gene-environment interactions, in which genetic susceptibility combines with teratogenic exposures during the first four to eight weeks of pregnancy when organs are forming. The timing specificity provides additional evidence for an embryonic blastogenic origin. During this crucial embryonic window,⁴ medications, alcohol, smoking, viruses, and other toxins may serve as insults. Current evidence identifies VATER as a multifactorial disorder resulting from the interaction between genetic susceptibilities and early-pregnancy environmental disturbances.

Diagnostic criteria

It has been difficult to establish diagnostic criteria for VATER/VACTERL due to the variable presentation. In the absence of a confirmatory laboratory test or genetic anomaly, the diagnosis is based on recognising a pattern of identifying characteristics.⁵ The majority of clinicians require the presence of at least three fundamental malformations for a diagnosis.⁵ Typical examples are vertebral defects, anal atresia, and Tracheo-Esophageal fistula. Additional criteria strongly supporting the diagnosis include cardiac anomalies, renal anomalies, a single umbilical artery, prenatal growth retardation, and limb defects.⁶ Regarding the minimum criteria, optimal diagnostic guidelines, and inclusion/exclusion of specific defects, however, there is substantial disagreement. Defining stringent diagnostic standards beyond identifying a non-random concentration of anomalies in two or more body systems is hampered by the highly heterogeneous nature. While some have proposed point systems and calculators to aid in diagnosis, the majority of experts emphasise clinical judgement based on the constellation of malformations present as opposed to strictly implementing predefined criteria.⁶

Clinical traits

The signs and symptoms of the VATER/VACTERL association depend on the specific anomaly patterns present in each individual. The severity of the symptoms can range from moderate to severe.

Vertebral variations

Approximately 60-80% of patients,⁷ are reportedly affected by vertebral defects. Vertebral segmentation defects, hemivertebrae, supernumerary or absent vertebrae, and fusion defects of the cervical, thoracic, and lumbar spine⁸ are common abnormalities. Scoliosis is commonly observed. Myelomeningocele is a rare disorder. Depending on the type and location of these vertebral anomalies, they can cause stunted growth or impaired mobility.

Anal atresia

The incidence of imperforate anus ranges from 55% to 90%, with both low and high forms observed.⁹ Also possible are anal stenosis and anteriorly displaced anus. Typically, early-life surgery is required to correct anal malformations and preserve gastrointestinal function.

Cardiac anomalies

50 to 80 % of patients with VATER/VACTERL  have congenital cardiac defects. Tetralogy of Fallot, ventricular septal defect, and atrial septal defect are the most prevalent heart abnormalities. Depending on the severity of the defect, cyanosis, cardiac failure, and other complications may occur.

Tracheoesophageal malformations

In 50-70% of cases, tracheoesophageal fistula or esophageal atresia is observed.¹¹ If not repaired, these can cause respiratory compromise, choking, aspiration, and nutrition difficulties. Later in life, oesophagal stenosis may also confound treatment. 

Renal anomalies

50-80 % of patients¹² exhibit renal anomalies. Horseshoe kidney, cystic renal dysplasia, renal agenesis/hypoplasia, and ureteral duplications are among the typical defects reported. Over time, these conditions frequently predispose to infections, kidney stones, and renal failure.  

Limb defects

In 40-50% of cases,¹³ limb abnormalities are evident. The most prevalent are radial anomalies, including hypoplasia and aplasia. Also prevalent are clubfoot, polydactyly, syndactyly, and hip dislocations. Anomalies of the limbs can substantially impair motor function and activity participation.

Other associated findings

Other characteristics that may be observed in VATER/VACTERL include:

• Single umbilical artery
• Cryptorchidism
• Abdominal organ malformations
• Craniofacial abnormalities
• Microcephalic head
• Hearing loss
• Cleft of the
• Later-life cardiac arrhythmias
• Growth deficiency

Diagnostic evaluations

Due to the complexity of the potential symptoms, infants suspected of having VATER/VACTERL require extensive evaluations.⁶ These may include a detailed prenatal and family history, a physical evaluation for dysmorphic features, imaging studies (spinal, limb, cardiac, and renal), an anorectal exam under anaesthesia, tracheobronchoscopy, esophagoscopy, chromosomal analysis, and laboratory tests to evaluate organ functions.^7,13 Clinicians are able to recognise the pattern of malformations that establishes the diagnosis of VATER/VACTERL association⁴ by integrating findings from the clinical history, physical exam, genetic tests, and a variety of imaging modalities. Despite the fact that some guidelines have been proposed, there are no universally acknowledged definitive criteria beyond the presence of anomalies in at least two organ systems.¹⁰ Due to the lack of a confirmatory laboratory test, clinical judgement based on the constellation of defects continues to be essential for an accurate diagnosis.^4,5 Thorough evaluation by a coordinated team of paediatric specialists is crucial to completely delineate the spectrum of anomalies present in each child.

Multidisciplinary management

Multiple paediatric subspecialties are required for the management of VATER/VACTERL association in order to address the spectrum of anomalies present in each child. Early surgical intervention is crucial for optimising outcomes and preventing complications.¹⁴ Orthopaedic, colorectal, cardiac, thoracic, and general surgeons frequently work together to treat vertebral defects, anal atresia, cardiac malformations, Tracheo-Esophageal fistula, and other anatomical conditions. Physical and occupational therapy aids in improving motor skills and addressing developmental delays caused by spinal, limb, or other skeletal defects.^10,12,14 For infants with anal impairments, bowel regimens and dietary adjustments are crucial. The field of cardiology provides ongoing monitoring and treatment for all cardiac conditions.¹⁰ Nephrology seeks to prevent urinary tract infections and renal stones and maintain kidney function in patients with genitourinary anomalies. Hearing loss is aided by audiological evaluations and treatment.¹² Psychosocial support addresses families' coping difficulties.¹⁵ The principal paediatrician coordinates care across specialities, monitors development, and manages related health concerns. Intensive initial intervention is crucial, but long-term multidisciplinary follow-up is required to monitor for and promptly treat any potential delayed complications or delayed sequelae.

Prognosis

The prognosis for infants with VATER/VACTERL association is dependent on the severity of anomalies and the speed of intervention. Overall survival rates approach 85 to 100 %, but morbidity is prevalent.¹⁶ Those with extensive cardiac defects, tracheo-esophageal abnormalities, and multiple affected systems have a higher incidence of complications.¹⁶ With coordinated speciality care, many afflicted children can have development and functional outcomes that are relatively typical. However, it is not uncommon for chronic medical issues to persist into adulthood and beyond. It is essential to provide continued follow-up care to monitor for and promptly treat any delayed sequelae.

Conclusion

In conclusion, VATER syndrome is a complex congenital condition characterised by multiple anomalies whose severity and clinical impact can vary considerably. While the precise aetiology remains unknown, research points to genetic predispositions and embryonic environmental disruptors as possible contributors. Diagnosis relies on the recognition of a characteristic pattern of vertebral, anorectal, cardiac, tracheal, renal and limb defects rather than a specific confirmatory test. Management focuses on surgical correction of anomalies, multidisciplinary medical care, and developmental interventions. With timely interventions, many affected children can have a decent quality of life, although it is not uncommon for them to experience some degree of chronic problems. It is necessary to conduct additional research to elucidate genetic markers, refine diagnostic criteria, develop targeted therapies, and enhance long-term outcomes. However, careful coordination of speciality care offers the greatest potential for positive health and developmental outcomes for affected children. It is recommended to conduct lifelong monitoring and management of any delayed sequelae or complications.