Exploring connections between genetics and pulmonary hypertension
TBX4 variants and deletions are associated with abnormal distal lung development, persistent pulmonary hypertension of a newborn, and pediatric pulmonary hypertension, as well as multiple congenital anomalies and developmental disabilities. Those are the findings of Boston Children’s Mary Mullen, MD; Pankaj Agrawal, MD; and several pediatric clinicians from around the world, who researched the spectrum of clinical manifestations associated with TBX4 genetic variants in newborns and children with pulmonary hypertension. Their findings are helping us better understand how pulmonary vascular disease manifests, and they will be key in further research that aims to discover cures.
A first-of-its-kind characterization of pulmonary hypertension
To collect more robust and high-quality data about the range of diseases, their natural histories, and optimal care for children with pulmonary hypertension, Dr. Mullen and Boston Children’s Lynn Sleeper, ScD, along with other researchers, characterized the distribution and clinical features associated with pediatric pulmonary hypertension, as defined by World Symposia on Pulmonary Hypertension classifications. They determined nearly half of patients enrolled in a pulmonary hypertension registry had pulmonary hypertension because of lung disease. Their findings reflect growing recognition of pulmonary hypertension in diverse developmental lung diseases and how improving the phenotyping of a child’s DNA sequence, based on these disease-specific characterizations, could improve pulmonary hypertension care and research.
Lung transplantation a possible path for end-stage pulmonary hypertension
The post-lung transplant recovery of patients with pulmonary hypertension and right ventricular dysfunction has not been well-detailed, prompting persistent questions about their stay in the hospital during a transplant procedure, as well as their cardiac function after transplantation. Dr. Mullen, Boston Children’s Gary Visner, DO; Francis Fynn-Thompson, MD; and other researchers found that all transplant pulmonary hypertension patients who also had right ventricular dysfunction were shown to have improved right ventricular function following transplantation — justifying the consideration of a lung transplant for pediatric patients with end-stage pulmonary hypertension and right ventricular dysfunction.
Examining hemodynamics and outcomes in BPD patients
Although cardiac catheterization is ideal for diagnosing pulmonary hypertension, it carries risks for infants and young children who have bronchopulmonary dysplasia (BPD)-pulmonary hypertension. As a result, research on these patients is lacking because studies often rely on diagnoses that were reached through an echocardiogram, which doesn’t measure blood pressure (hemodynamics) as accurately as catheterization does. In a multi-center study, Dr. Mullen and others reviewed Pediatric Pulmonary Hypertension Network (PPHNet) data to determine whether children with grade 3 BPD-pulmonary hypertension would have severe hemodynamics measurements assessed by catheterization. Read the findings of their research.
Learning more about SOX17 and pulmonary arterial hypertension
We’re looking at how variants of the gene SOX17 might contribute to pulmonary arterial hypertension (PAH), a severe form of pulmonary hypertension that leads to severe congenital heart disease (CHD). A recent multi-center study led by our team suggests that SOX17 variants should be considered in children with PAH who have severely elevated right ventricle pressures, peripheral pulmonary artery stenosis, and other cardiovascular issues — which could distinguish SOX17-related PAH from other PAH genetic disorders.
