Expert Reviewed By: Dr. Brandon Colby MD
VACTERL association is a rare congenital disorder characterized by a combination of birth defects affecting various organ systems. The acronym VACTERL stands for Vertebral anomalies, Anal atresia, Cardiac malformations, Tracheoesophageal fistula, Esophageal atresia, Renal anomalies, and Limb abnormalities. Although the exact cause of VACTERL association is still unknown, recent studies have provided evidence for the involvement of genetic factors in the development of this disorder. This article will discuss the latest research on understanding, diagnosing, and using genetic testing for VACTERL association.
Understanding the Genetic Factors in VACTERL Association
Several studies have highlighted the role of genetic factors in the development of VACTERL association. Familial occurrence, chromosomal aberrations, and single gene mutations have been reported in affected individuals, suggesting a genetic component to the disease2. In particular, researchers have identified disease genes, such as FGF8, FOXF1, HOXD13, LPP, TRAP1, and ZIC3, which are associated with the renal phenotype of VACTERL association1. These findings provide valuable insights into the underlying genetic factors of the disorder and pave the way for the development of more targeted diagnostic and treatment strategies.
Diagnosing VACTERL Association
Diagnosing VACTERL association can be challenging due to the wide variability in the presentation of the disorder. The diagnosis is typically based on the presence of at least three of the VACTERL features in an affected individual. However, the absence of a specific diagnostic test means that the diagnosis relies heavily on clinical evaluation and imaging studies, such as X-rays, ultrasounds, and magnetic resonance imaging (MRI). The identification of genetic factors associated with VACTERL association has opened up new possibilities for more accurate diagnosis using genetic testing.
Genetic Testing for Chromosomal Aberrations and Single Gene Mutations
Genetic testing can be helpful in identifying chromosomal aberrations and single gene mutations associated with VACTERL association. For example, a study using array comparative genomic hybridization (array-CGH) identified pathogenic gene dose imbalances in two fetal cases of VACTERL association and a pathogenic mutation in the CHD7 gene3. This type of testing can provide valuable information about the genetic factors underlying the disorder and can aid in the diagnosis and management of affected individuals.
Exome Sequencing and Microarray Analysis
Exome sequencing and microarray analysis are powerful tools for identifying genetic factors associated with complex disorders like VACTERL association. In a study of monozygotic twin pairs discordant for features of VACTERL association, researchers used exome sequencing and high-density microarray testing to explore the genetic factors underlying the disorder4. Although the study concluded that challenges remain in applying these methods to the diagnosis of VACTERL association, it demonstrated the potential of these advanced techniques in identifying genetic factors associated with the disorder.
The Future of Genetic Testing in VACTERL Association
As researchers continue to uncover the genetic factors involved in VACTERL association, the role of genetic testing in the diagnosis and management of this disorder is expected to grow. Genetic testing can provide valuable information about the underlying genetic factors, helping clinicians to make more accurate diagnoses and tailor treatment plans to the specific needs of affected individuals. Furthermore, genetic testing can also be used to identify at-risk family members and provide genetic counseling for families affected by VACTERL association.
In conclusion, the identification of genetic factors associated with VACTERL association has opened up new possibilities for understanding, diagnosing, and managing this complex congenital disorder. As our knowledge of the genetic factors involved in VACTERL association continues to grow, so too will the potential for more targeted diagnostic and treatment strategies using genetic testing.
About The Expert Reviewer
Dr. Brandon Colby MD is a US physician specializing in the personalized prevention of disease through the use of genomic technologies. He’s an expert in genetic testing, genetic analysis, and precision medicine. Dr. Colby is also the Founder of and the author of Outsmart Your Genes.
Dr. Colby holds an MD from the Mount Sinai School of Medicine, an MBA from Stanford University’s Graduate School of Business, and a degree in Genetics with Honors from the University of Michigan. He is an Affiliate Specialist of the American College of Medical Genetics and Genomics (ACMG), an Associate of the American College of Preventive Medicine (ACPM), and a member of the National Society of Genetic Counselors (NSGC)