Pharmacogenomics of Pediatric Cardiac Arrest: Cisplatin Treatment Worsened by a Ryanodine Receptor 2 Gene Mutation

Angela Maggio,Saverio Ladogana,Domenico Rosario Potenza,Massimo Carella,Anita Spirito,Mauro Pellegrino Salvatori,Massimo Villella,Maria Pia Leone,Sandra Mastroianno,Stefano Castellana,Pietro Palumbo,Giuseppe Di Stolfo,Marco Castori

doi:10.3390/cardiogenetics12010007

Angela Maggio, Saverio Ladogana + Show 11 more

Open Access

https://doi.org/10.3390/cardiogenetics12010007

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Abstract

In thelast few decades, the roles of cardio-oncology and cardiovascular geneticsgained more and more attention in research and daily clinical practice, shaping a new clinical approach and management of patients affected by cancer and cardiovascular disease. Genetic characterization of patients undergoing cancer treatment can support a better cardiovascular risk stratification beyond the typical risk factors, suchas contractile function and QT interval duration, uncovering a possible patient’s concealed predisposition to heart failure, life threatening arrhythmias and sudden death. Specifically, an integrated cardiogenetic approach in daily oncological clinical practice can ensure the best patient-centered healthcare model, suggesting, also the adequate cardiac monitoring timing and alternative cancer treatments, reducing drug-related complications. We report the case of a 14-month-old girl affected by neuroblastoma, treated by cisplatin, complicated by cardiac arrest. We described the genetic characterization of a Ryanodine receptor 2 (RYR2) gene mutation and subsequent pharmacogenomic approach to better shape the cancer treatment.

Highlights

Background published maps and institutional affilIn the last few decades, the roles of cardio-oncology and cardiovascular geneticsgainedmore and more attention in research and daily practice, shaping a new clinical approach and management of patients affected by cancer and cardiovascular disease
After Sanger sequencing of the proband’s parents, the Ryanodine receptor 2 (RYR2) variants resulted to be inherited from the mother, while both parents were heterozygous the GJB2 variant
Serum electrolytes concentration was normal in the morning, before the cardiac arrest; in particular magnesium level, as it is an important RyR2 regulator, a potential mechanism by which Cisplatin may promote RyR2 hiperactivity duringhipomagnesemia

Summary

Introduction

In the last few decades, the roles of cardio-oncology and cardiovascular geneticsgainedmore and more attention in research and daily practice, shaping a new clinical approach and management of patients affected by cancer and cardiovascular disease As it is common practice when something new is discovered, scientists and clinicians followsuper specialized pathways to investigate in detail each single brick of the new process, while the final aim is to manage each patient in their own fragmented complexity [1]. In this regard, the genetic characterization of patients undergoing cancer treatment could allow a better cardiovascular risk stratification beyond the typical risk factors, such as contractile function and QT interval duration, uncovering a possible patient’s concealed predisposition to heart failure, life threatening arrhythmias and sudden death. An integrated cardiogenetic approach in daily oncological clinical practice will ensure the best iations.

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