From the Guidelines
The FLT4 gene is not typically associated with truncus arteriosus, and current evidence does not support it as a major contributor to this condition. Truncus arteriosus is a rare congenital heart defect where the blood vessel coming out of the heart fails to separate completely into the pulmonary artery and aorta. The primary genes implicated in truncus arteriosus are NKX2.5, TBX1, and GATA6, with the 22q11.2 deletion syndrome (DiGeorge syndrome) being a common genetic cause, as suggested by 1. FLT4, which encodes vascular endothelial growth factor receptor 3 (VEGFR3), is primarily associated with lymphatic vessel development and hereditary lymphedema conditions rather than cardiac outflow tract defects.
While FLT4 plays roles in cardiovascular development, the most recent and highest quality study, 1, does not mention FLT4 as a contributor to truncus arteriosus. Instead, it focuses on the management of adults with congenital heart disease, including those with truncus arteriosus, and emphasizes the importance of comprehensive genetic evaluation.
Some key points to consider in the management of truncus arteriosus include:
- Genetic testing typically focuses on the 22q11.2 region and other cardiac developmental genes rather than FLT4, as recommended by 1 and 1.
- Comprehensive genetic evaluation should be considered for patients with truncus arteriosus, focusing on established genetic causes rather than FLT4, as suggested by 1.
- Management of truncus arteriosus in adults may involve assessment and treatment of pulmonary hypertension, aortic valve disease, and aortopathies, as discussed in 1 and 1.
In summary, the FLT4 gene is not a primary concern in the diagnosis or management of truncus arteriosus, and genetic testing should focus on established genetic causes, such as the 22q11.2 deletion syndrome, as recommended by 1 and 1.
From the Research
Truncus Arteriosus and Genetic Associations
- Truncus arteriosus is a rare congenital heart defect characterized by a single arterial trunk that supplies systemic, pulmonary, and coronary circulations 2.
- The presence of associated cardiac and extracardiac manifestations as well as genetic anomalies is common in truncus arteriosus, with a 22q11 microdeletion identified in 27% of tested cases 2.
- However, there is no direct evidence in the provided studies to suggest that the flt4 gene is responsible for truncus arteriosus.
Surgical Repair and Outcomes
- Surgical repair of truncus arteriosus can be performed safely with low morbidity and mortality, both in neonates, infants, and older children 3, 4.
- Early surgical intervention is crucial for improving long-term outcomes, although the condition is still associated with significant risks 2, 5.
- Re-intervention is common, preferably through a transcatheter approach, with freedom from reintervention being 86% at 1 year, 75% at 2 years, and 65% at 3 years 3.
Associated Conditions and Comorbidities
- Truncus arteriosus is often associated with other congenital malformations, including DiGeorge syndrome, prematurity, and other congenital heart defects 6.
- Interrupted aortic arch is an associated malformation that significantly impacts the complexity of the truncus arteriosus operation, with patients having a longer post-operative length of stay compared to those without interrupted aortic arch 6.