Genetic Evidence for Congenital Vascular Disorders in Patients with VACTERL Association

Introduction The VACTERL association is a rare malformation complex, showing at least three anomalies of the following organ systems: vertebra, anorectum, heart and vessels, trachea and esophagus, genitourinary tract, and limbs. In addition to a multifactorial event, congenital vascular disorders are also discussed as triggers for the VACTERL association. The aim of this study was to determine whether there is a genetic background for vascular disorders triggering VACTERL association. Materials and Methods We performed a functional analysis on whole exome sequencing data of 21 patients with VACTERL or VACTERL-like phenotype using the online analysis tool “Database for Annotation, Visualization and Integrated Discovery (DAVID) v6.8.” The study was approved by the institutional ethics committee (approval no. 026–13). Written informed consent was obtained from all patients or their parents. Results We identified a total of 86 genetic variants (in 75 genes) classified as damaging (including probably damaging missense, nonsense, and frameshift variants), which are associated to cardiovascular development. Each investigated patient showed at least one damaging variant in genes associated to cardiovascular development. These variants were further reduced by significance in cardiovascular development to 39 genetic variants (in 33 genes). Of note, a pair of siblings, both presenting with cardiac and renal defects, had the same damaging variant in two different genes. Conclusion Our results indicate a genetic background for congenital vascular disorders in patients with VACTERL association. In line with the literature, our data suggest that genetic mutation led to vascular diseases, which in turn may cause malformations similar to the VACTERL association.

Co-Existence of a Rudimentary Non-Communicating Horn with a Unicornuate Uterus in Association with 2 Components of the VACTERL Association: A Case Report

The prevalence of congenital uterine anomalies has been reported as 6.7% in the general population. The unicornuate uterus accounts for 2.4-13% of all Mullerian anomalies and has a prevalence of 1:1000. A unicornuate uterus may be present alone or with a rudimentary horn and 75-90% of rudimentary horns are non-communicating. A pregnancy in the rudimentary horn may lead to uterine rupture, haemoperitoneum with a high risk of maternal mortality. The association of a unicornuate uterus with a non-communicating uterine horn to the VACTERL association of defects (vertebral anomalies, anorectal malformations, cardiovascular anomalies, tracheoesophageal fistula, esophageal atresia, renal anomalies and limb defects) has been described only twice in the literature. We report a patient who was born with an extra thumb and had a trachea-bronchial remnant with oesophageal stenosis that were both operated on earlier, and they were associated with a non-communicating rudimentary uterine horn. To the best of our knowledge, this is the third case reported in the literature of a VACTERL association to a unicornuate uterus with a non-communicating functional rudimentary horn. Given the high risk for the patient if pregnant an early diagnosis is paramount. This case highlights the importance of considering Mullerian defects in the young patient born with components of the VACTERL association.

Triple Atresia, Triple Threat? An Unusual Constellation of Primary Surgical Abnormalities

We present a case series of two patients with tracheo-oesophageal fistula with oesophageal atresia (TOF/OA), duodenal atresia (DA) and ano-rectal malformation (ARM). This constellation of abnormalities, dubbed triple atresia (TA), is a rare combination with few described cases in the literature. Here we describe our management of these cases, as well as the results of our literature review. Both of our cases had staged surgical procedures and were initially managed with thoracotomy for repair of TOF/OA on day two of life. They subsequently underwent laparotomy for management of their abdominal pathology at day five and seven of life. Both have survived the neonatal period and are awaiting definitive surgery for ARM. Literature review yielded seven cases of TA involving a TOF, DA, and ARM. Four patients underwent staged repair, while three patients underwent repair of TOF/OA, DA and colostomy for ARM at the same time. Of these three patients, two died, representing 22% of the overall cohort. Triple atresia remains a rare subset of patients suspected to have VACTERL association, however mortality may be significantly higher. Our data would suggest a staged approach to be optimal for long term survival.

A case report of VACTERL syndrome (anorectal, cardiac and renal malformations)

Introduction. VACTERL is a rare condition, named after the spectrum of malformations characterizing it: vertebral/vas­cu­lar anomalies, anal atresia, cardiac malformations, tracheo-esophageal fistula, renal anomalies, limb ano­ma­lies. Case presentation. We report the case of a male infant who presented in our clinic with the suspicion of inborn error of metabolism due to the severe metabolic acidosis and hypoglycemia. He was operated in the second day of life for imperforate anus and rectoperineal fistula. The radiological examination revealed severe bronchopneumonia for which he required antibiotic treatment and electrolyte infusions for the correction of the acidosis. Starting from the anorectal anomalies, we performed imagistic investigations that detected atrial septal defect and unilateral kidney agenesis. Based on the presence of three specific anomalies, we could establish the diagnosis of VACTERL association and we started the supportive treatment. Conclusions. VACTERL association is a complex spectrum of malformations, some of them with high mortality if they are not corrected on the right moment.

CAUDAL REGRESSION AND VACTERL ASSOCIATION IN A CHILD FROM MULTIPLE PREGNANCY (TWINS) AFTER THE USE OF ASSISTED REPRODUCTIVE TECHNOLOGIES

The article presents a case of a very rare malformations combination in a child born from multiple pregnancy (twins) after in vitro fertilization. The premature boy was born the second at 35,4 weeks by caesarean section for premature membranes rupture. The child had malformations of the thoracic vertebrae, ribs, kidneys and urinary system, esophageal atresia with tracheoesophageal fistula, characteristic for VACTERL association. At the same time, other anomalies of the sacral spine, lower extremities and lower urinary tract matched the classic caudal regression syndrome. The data obtained in recent years indicate that abnormalities in the same genes can cause VACTERL association and caudal regression syndrome. The standard approach in the treatment of such patients involves surgical correction of abnormalities to provide adequate vital functions of gas exchange, hemodynamics and digestion. The clinical observation published in this study demonstrates the success of this approach in a patient with a combination of VACTERL association and caudal regression syndrome.