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Cardiac Manifestations in Tuberous Sclerosis Complex and Proposed Pathophysiologic Mechanisms: A Case Report and Literature Review

Ageliki A. Karatza1,2, Asimina Tsintoni1, Sotirios Fouzas1, Despoina Gkentzi1, Eirini Kostopoulou1, Xenophon Sinopidis1, Nikolaos Antonakopoulos3, John Papagiannis2

1Department of Paediatric Cardiology, University of Patras Medical School, Greece

2Department of Paediatrics and Adult Congenital Heart Disease, “Onassis” Cardiothoracic Centre, Athens, Greece

3Department of Obstetrics and Gynaecology, Division of Maternofetal Medicine, University of Patras Medical School, Greece

*For Correspondence

agelikikaratza@hotmail.com

karatza@upatras.gr

Publication Date: March 23, 2026
DOI: 10.5281/zenodo.14830096
Read Abstract

Introduction: Tuberous sclerosis complex (TSC) is a rare autosomal dominant syndrome that presents with complex clinical features and involves multiple human systems. Many manifestations can be associated with severe morbidity and mortality, usually those of the central nervous and cardiovascular system.

Cardiovascular manifestations of TSC: Cardiac rhabdomyoma is often the earliest manifestation TSC, typically appearing during the prenatal period with an incidence between 70% and 90%. Although most are clinically silent, they can lead to serious and potentially life-threatening cardiovascular complications. In the past resolution of rhabdomyomas was considered the natural course of the disease. It has recently been documented re-appearance of the rhabdomyomas in 12-15% of adolescent patients, an issue that increases the risk for future arrhythmias. TSC is a complex arrhythmic disorder associated with conductive effects irrespective of the presence of rhabdomyomas, which requires meticulous cardiac follow-up throughout the patient’s life. ECG findings include premature atrial contractions, paroxysmal supraventricular tachycardia, Wolff-Parkinson-White syndrome, sinoatrial nodal re-entrant tachycardia, atrial flutter, junctional rhythm, premature ventricular contractions, ventricular tachycardia and atrial tachycardia. Arterial aneurysms are another complication of TSC with an incidence which is double compared to the general population and can involve aorta, carotid, axillary, renal, iliac, femoral and pulmonary arteries.

mTOR inhibitor treatment of cardiac complications of TSC: The increasing understanding of the mTOR pathway activation in the pathophysiology of TSC has resulted in a progressive rise in the use of mTOR inhibitors for the management of patients with TSC, including those with rhabdomyomas and refractory arrhythmias.

Case presentation: A fetus with suspected tuberous sclerosis complex presenting with fetal arrhythmias in the absence of rhabdomyomas and various patterns of neonatal and infant arrhythmias treated with Everolimus persisting despite regression of rhabdomyomas.

Keywords

Tuberous Sclerosis Complex, Cardiac Rhabdomyomas, m-TOR inhibitors, Everolimus, Sirolimus, Fetal/Neonatal arrhythmias

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