Genetics dictating therapeutic decisions in pediatric pulmonary hypertension? A case report suggesting we are getting closer

Abstract

Abstract Despite therapeutic advances over the past decades, pulmonary arterial hypertension (PAH) and related pulmonary vascular diseases continue to cause significant morbidity and mortality in neonates, infants, and children. Unfortunately, an adequate understanding of underlying biology is lacking. There has been a growing interest in the role that genetic factors influence pulmonary vascular disease, with the hope that genetic information may aid in identifying disease etiologies, guide therapeutic decisions, and ultimately identify novel therapeutic targets. In fact, current data suggest that genetic factors contribute to ~42% of pediatric‐onset PH compared to ~12.5% of adult‐onset PAH. We report a case in which the knowledge that biallelic ATP13A3 mutations are associated with malignant progression of PAH in young childhood, led us to alter our traditional treatment plan for a 21‐month‐old PAH patient. In this case, we elected to perform a historically high‐risk Potts shunt before expected rapid deterioration. Short‐term follow‐up is encouraging, and the patient remains the only known surviving pediatric PAH patient with an associated biallelic ATP13A3 mutation in the literature. We speculate that an increased use of comprehensive genetic testing can aid in identifying the underlying pathobiology and the expected natural history, and guide treatment plans among PAH patients.

Keywords

• ATP13A3
• Potts shunt
• pulmonary vascular disease