Cardiac Rhabdomyomas in Children: A Comprehensive Review

Abstract

Cardiac rhabdomyomas are the most common primary cardiac tumors in children, often associated with tuberous sclerosis complex (TSC). These benign tumors can present with a spectrum of clinical manifestations, ranging from asymptomatic cases to life-threatening complications. This review comprehensively examines the epidemiology, pathogenesis, clinical presentation, diagnostic evaluation, and management strategies for cardiac rhabdomyomas in children. We discuss the role of echocardiography, cardiac magnetic resonance imaging (MRI), and other diagnostic modalities in the evaluation of these tumors. The review delves into the management strategies, including observation, medical therapy with mTOR inhibitors, and surgical intervention. We also discuss the association between cardiac rhabdomyomas and TSC, emphasizing the importance of a multidisciplinary approach to patient care. Finally, we explore current research directions and the future of cardiac rhabdomyoma management in the pediatric population.

Introduction

Cardiac rhabdomyomas, benign tumors originating from cardiac muscle, are the most common primary cardiac tumors in children. While often asymptomatic, they can present with a spectrum of clinical manifestations, ranging from asymptomatic cases to life-threatening complications such as heart failure, arrhythmias, and outflow tract obstruction. Furthermore, cardiac rhabdomyomas are frequently associated with tuberous sclerosis complex (TSC), a genetic disorder characterized by the development of hamartomas in multiple organs.

This review comprehensively examines the epidemiology, pathogenesis, clinical presentation, diagnostic evaluation, and management strategies for cardiac rhabdomyomas in children.

Epidemiology

• Prevalence:

  • Cardiac rhabdomyomas are estimated to account for approximately 25-30% of all pediatric cardiac tumors.

  • The true incidence is likely underestimated due to the presence of asymptomatic cases.

• Age of Presentation:

  • Can present at any age, but most commonly diagnosed during infancy or early childhood.

  • Prenatal diagnosis is increasingly common.

• Association with TSC:

  • Approximately 50-70% of children with cardiac rhabdomyomas have an underlying diagnosis of TSC.

  • TSC is an autosomal dominant genetic disorder caused by mutations in the TSC1 or TSC2 genes.

Pathogenesis

• Tumorigenesis:

  • Cardiac rhabdomyomas arise from the abnormal proliferation of cardiac muscle cells.

  • The pathogenesis is closely linked to the TSC-mTOR pathway.

  • In TSC, mutations in the TSC1 or TSC2 genes lead to dysregulation of the mammalian target of rapamycin (mTOR) signaling pathway.

  • This results in uncontrolled cell growth and proliferation, leading to the formation of hamartomas in various organs, including the heart.

Clinical Presentation

• Asymptomatic cases:

  • Frequently discovered incidentally on routine fetal echocardiography or during evaluation for other conditions.

• Symptomatic cases:

  • Heart failure:

    • Congestive heart failure (CHF) is a common presentation, manifested by tachypnea, dyspnea, feeding difficulties, hepatomegaly, and poor weight gain.

    • May be due to mass effect, such as obstruction of cardiac outflow tracts or impairment of ventricular filling.

  • Arrhythmias:

    • Atrial and ventricular arrhythmias, including supraventricular tachycardia and ventricular tachycardia, can occur.

    • Arrhythmias may be due to direct compression of the conduction system or myocardial dysfunction.

  • Outflow tract obstruction:

    • Left ventricular outflow tract obstruction (LVOTO) and right ventricular outflow tract obstruction (RVOT) can occur due to tumor compression.

  • Other manifestations:

    • Pericardial effusion

    • Hydrops fetalis (in severe cases)

Diagnostic Evaluation

• Fetal Echocardiography:

  • Plays a crucial role in prenatal diagnosis.

  • Allows for early identification and evaluation of tumor size, location, and hemodynamic impact.

  • Enables prenatal counseling and planning for delivery.

• Echocardiography:

  • Two-dimensional echocardiography: Essential for initial diagnosis and assessment of tumor size, location, and hemodynamic impact.

  • Doppler echocardiography: To assess for valvular regurgitation, shunts, and intracardiac shunts.

  • Three-dimensional echocardiography: Can provide more detailed anatomical information and improve visualization of complex tumors.

• Cardiac Magnetic Resonance Imaging (MRI):

  • Provides detailed anatomical information about the tumor, including size, shape, and extent of involvement.

  • Can assess myocardial function and detect extracardiac manifestations of TSC.

  • May be useful in preoperative planning for surgical intervention.

• Electrocardiography (ECG):

  • To assess for arrhythmias and evaluate cardiac rhythm.

• Electrophysiology studies:

  • May be indicated in cases of arrhythmias to assess the underlying mechanism and guide treatment.

• Genetic testing:

  • Genetic testing for TSC1/TSC2 gene mutations is recommended in all children with cardiac rhabdomyomas.

Management Strategies

• Observation:

  • Asymptomatic cases with small, non-obstructive tumors may be observed with serial echocardiographic follow-up.

  • Regular monitoring allows for early detection of tumor growth or the development of symptoms.

• Medical Therapy:

  • mTOR inhibitors (e.g., sirolimus, everolimus):

    • Have emerged as the mainstay of medical therapy for symptomatic cardiac rhabdomyomas.

    • Inhibit the mTOR signaling pathway, leading to tumor regression and improvement in cardiac function.

    • Require close monitoring for potential side effects, including infection, immunosuppression, and growth retardation.

• Surgical Intervention:

  • Indicated in cases of:

    • Severe hemodynamic compromise refractory to medical therapy.

    • Large, obstructive tumors.

    • Life-threatening arrhythmias.

  • Surgical options may include:

    • Tumor resection (e.g., myectomy, resection of atrial or ventricular septal defects)

    • Palliative procedures (e.g., septal myectomy for LVOTO)

Tuberous Sclerosis Complex (TSC)

• Evaluation for TSC:

  • Comprehensive evaluation for other manifestations of TSC, including:

    • Cutaneous lesions (e.g., angiofibromas, hypomelanotic macules, shagreen patches)

    • Neurological manifestations (e.g., seizures, intellectual disability, autism spectrum disorder)

    • Renal angiomyolipomas

    • Pulmonary lymphangioleiomyomatosis

• Management of TSC:

  • Multidisciplinary approach involving cardiologists, neurologists, nephrologists, dermatologists, and genetic counselors.

  • Management of TSC-related manifestations requires a tailored approach based on individual patient needs.

Prognosis

• Prognosis varies depending on several factors:

  • Tumor size and location

  • Presence of associated complications (e.g., heart failure, arrhythmias)

  • Presence of TSC

  • Response to treatment

• Spontaneous regression:

  • Spontaneous regression of cardiac rhabdomyomas can occur, particularly in asymptomatic cases.

• Long-term follow-up:

  • Long-term follow-up is crucial to monitor for tumor growth, assess for the development of complications, and evaluate the long-term impact on cardiac function and overall health.

Future Directions

• Continued research:

  • Investigate the long-term efficacy and safety of mTOR inhibitors in the management of cardiac rhabdomyomas.

  • Explore the role of novel therapeutic approaches, such as immunotherapy and gene therapy.

  • Develop predictive models to identify patients at high risk for complications.

• Improve risk stratification:

  • Develop more accurate risk stratification models to identify patients who may benefit most from aggressive treatment.

• Enhance multidisciplinary care:

  • Foster collaboration among cardiologists, geneticists, neurologists, and other specialists to ensure optimal management of patients with cardiac rhabdomyomas and TSC.

Conclusion

Cardiac rhabdomyomas are an important cause of cardiac tumors in children. Early diagnosis, comprehensive evaluation, and a multidisciplinary approach to management are crucial for optimal outcomes. Continued research is essential to improve our understanding of these tumors, optimize treatment strategies, and improve long-term outcomes for affected children.