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Turkish Journal of Medical Sciences Nov 2020Tuberous sclerosis complex (TSC) is an autosomal dominant, multisystem disorder that is characterized by cellular and tissue dysplasia in several organs. With the advent... (Review)
Review
Tuberous sclerosis complex (TSC) is an autosomal dominant, multisystem disorder that is characterized by cellular and tissue dysplasia in several organs. With the advent of genetic and molecular techniques, mutations in the TSC1 or TSC2 genes were discovered to be responsible for mTOR overactivation, which is the underlying mechanism of pathogenesis. TSC is a highly heterogenous clinical entity with variable presentations and severity of disease. The brain, heart, skin, eyes, kidneys, and lungs are commonly involved in this syndrome, with neurologic symptoms comprising a significant source of morbidity and mortality. In 2012, the diagnostic criteria for TSC were revised by the International Tuberous Sclerosis Complex Consensus panel, and genetic testing was incorporated into the guidelines. Early detection of cardiac rhabdomyomas or TSC-associated skin lesions can suggest the diagnosis and underlie the importance of clinical vigilance. Animal studies have demonstrated the benefit of using mTOR inhibitors for various symptoms of TSC, and they have been successfully translated into clinical trials with significant improvement in symptom burden. Subependymal giant cell astrocytomas, renal angiomyolipomas, and epilepsy are the three FDA-approved indications in relation to TSC for the use of everolimus, which is a first generation mTOR inhibitor. Rapamycin has been FDA approved for lymphangioleiomyomatosis. Other TSC symptoms that could potentially benefit from this class of medication are currently under investigation. TSC constitutes a unique combination of protean physical symptoms and neurobehavioral abnormalities. TSC associated neuropsychiatric disorders (TAND), including intellectual disability, mood disorders, and autism spectrum disorder, represent significant challenges but remain underdiagnosed and undertreated. The TAND checklist is a useful tool for routine use in the clinical evaluation of TSC patients. A multidisciplinary treatment plan, based on the specific problems and needs of individuals, is the key to management of this genetic condition. Ongoing research studies have been providing promising leads for developing novel mechanistic strategies to address the pathophysiology of TSC.
Topics: Animals; Brain; Epilepsy; Humans; TOR Serine-Threonine Kinases; Tuberous Sclerosis; Tuberous Sclerosis Complex 1 Protein; Tuberous Sclerosis Complex 2 Protein
PubMed: 32222129
DOI: 10.3906/sag-2002-133 -
Cureus Apr 2021Cardiac rhabdomyoma is a hamartoma comprised of cardiac myocytes. It is the classic cardiac manifestation of tuberous sclerosis complex (TSC) which is an autosomal...
Cardiac rhabdomyoma is a hamartoma comprised of cardiac myocytes. It is the classic cardiac manifestation of tuberous sclerosis complex (TSC) which is an autosomal dominant genetic syndrome with multi-organ involvement, but highly variable phenotype. Cardiac rhabdomyoma is most commonly diagnosed in infancy, 70 to 90% of whom have TSC. However, TSC-associated cardiac rhabdomyoma usually shows spontaneous regression within the first two years of life and hence is extremely rare in adults. We present a 34-year-old woman with TSC who was found to have a cardiac rhabdomyoma when she was referred to the cardiology clinic for evaluation and to establish care. Cardiac rhabdomyoma is usually asymptomatic. However, depending on size and location, it can cause outflow or inflow tract obstruction and aberrant electrical conduction. Hence, appropriate surveillance is important.
PubMed: 34026381
DOI: 10.7759/cureus.14565 -
Journal of Cardiovascular Echography 2022Studying cardiac masses is one of the most challenging tasks for cardiac imagers. The aim of this review article is to focus on the modern imaging of cardiac masses... (Review)
Review
Studying cardiac masses is one of the most challenging tasks for cardiac imagers. The aim of this review article is to focus on the modern imaging of cardiac masses proceeding through the most frequent ones. Cardiac benign masses such as myxoma, cardiac papillary fibroelastoma, rhabdomyoma, lipoma, and hemangioma are browsed considering the usefulness of most common cardiovascular imaging tools, such as ultrasound techniques, cardiac computed tomography, cardiac magnetic resonance, and in the diagnostic process. In the same way, the most frequent malignant cardiac masses, such as angiosarcoma and metastases, are highlighted. Then, the article browses through nontumoral masses such as cysts, mitral caseous degenerative formations, thrombi, and vegetations, highlighting the differential diagnosis between them. In addition, the article helps in recognizing anatomic normal variants that should not be misdiagnosed as pathological entities.
PubMed: 36249434
DOI: 10.4103/jcecho.jcecho_18_22 -
Pharmacological Research Sep 2023Tuberous sclerosis complex (TSC) is an autosomal dominant disease characterised by abnormal cell proliferation and differentiation that affects multiple organs and can... (Review)
Review
Tuberous sclerosis complex (TSC) is an autosomal dominant disease characterised by abnormal cell proliferation and differentiation that affects multiple organs and can lead to the growth of hamartomas. Tuberous sclerosis complex is caused by the disinhibition of the protein mTOR (mammalian target of rapamycin). In the past, various therapeutic approaches, even if only symptomatic, have been attempted to improve the clinical effects of this disease. While all of these therapeutic strategies are useful and are still used and indicated, they are symptomatic therapies based on the individual symptoms of the disease and therefore not fully effective in modifying long-term outcomes. A new therapeutic approach is the introduction of allosteric inhibitors of mTORC1, which allow restoration of metabolic homeostasis in mutant cells, potentially eliminating most of the clinical manifestations associated with Tuberous sclerosis complex. Everolimus, a mammalian target of the rapamycin inhibitor, is able to reduce hamartomas, correcting the specific molecular defect that causes Tuberous sclerosis complex. In this review, we report the findings from the literature on the use of everolimus as an effective and safe drug in the treatment of TSC manifestations affecting various organs, from the central nervous system to the heart.
Topics: Humans; Everolimus; Tuberous Sclerosis; Sirolimus; Mechanistic Target of Rapamycin Complex 1
PubMed: 37549757
DOI: 10.1016/j.phrs.2023.106884 -
The Turkish Journal of Pediatrics 2023Primary cardiac tumors are extremely rare. Cardiac rhabdomyoma is the most common primary cardiac tumor. 50-80% of solitary rhabdomyomas and all multiple rhabdomyomas...
BACKGROUND
Primary cardiac tumors are extremely rare. Cardiac rhabdomyoma is the most common primary cardiac tumor. 50-80% of solitary rhabdomyomas and all multiple rhabdomyomas are associated with tuberous sclerosis complex. Due to spontaneous regression, surgery is necessary only in severe hemodynamic compromise and persistent arrhythmias. Everolimus, a mechanistic target of rapamycin (mTOR) inhibitor, can be used in the treatment of rhabdomyomas seen in tuberous sclerosis complex. We aimed to evaluate the clinical progression of rhabdomyomas followed-up in our center between the years 2014-2019 and evaluate the efficacy and safety of everolimus treatment on tumor regression.
METHODS
Clinical features, prenatal diagnosis, clinical findings, tuberous sclerosis complex presence, treatment and follow-up results were evaluated retrospectively.
RESULTS
Among 56 children with primary cardiac tumors, 47 were diagnosed as rhabdomyomas, 28/47 patients (59.6%) had prenatal diagnosis, 85.1% were diagnosed before one year of age and 42/47 patients (89.3%) were asymptomatic. Multiple rhabdomyomas were present in 51% and median diameter of tumors was 16mm (4.5 - 52 mm). In 29/47 patients (61.7%) no medical or surgical treatment were necessary while 34% of these had spontaneous regression. Surgery was necessary in 6/47 patients (12.7%). Everolimus was used in 14/47 patients (29.8%). Indications were seizures (2 patients) and cardiac dysfunction (12 patients). Regression in size of rhabdomyomas was achieved in 10/12 patients (83%). Although, in the long-term, the amount of tumor mass shrinkage was not significantly different between patients who received everolimus and untreated patients (p=0.139), the rate of mass reduction was 12.4 times higher in patients who received everolimus. Leukopenia was not detected in any of the patients, but, hyperlipidemia was noted in 3/14 patients (21.4%).
CONCLUSIONS
According to our results, everolimus accelerates tumor mass reduction, but not amount of mass regression in the long term. Everolimus may be considered for treatment of rhabdomyomas which cause hemodynamic compromise or life-threatening arrhythmias before surgical intervention.
Topics: Child; Pregnancy; Female; Humans; Adult; Everolimus; Rhabdomyoma; Tuberous Sclerosis; Retrospective Studies; Heart Neoplasms; Cardiomyopathies; Disease Progression
PubMed: 37395967
DOI: 10.24953/turkjped.2022.922 -
Journal of Medical Case Reports Apr 2022Cardiac tumors in infants and children are rare. The most common cardiac tumor is rhabdomyoma, which may be associated with tuberous sclerosis. However, not all cardiac...
BACKGROUND
Cardiac tumors in infants and children are rare. The most common cardiac tumor is rhabdomyoma, which may be associated with tuberous sclerosis. However, not all cardiac rhabdomyomas are pathognomonic for tuberous sclerosis, and not all congenital cardiac tumors are rhabdomyomas. During the prenatal period, early cardiac tumor detection provides important information about fetal wellbeing, delivery planning, and necessary postnatal care.
CASE PRESENTATION
We report a 36-year-old African American pregnant women. At 32 weeks 5 days gestational age, the male fetus had a fetal echocardiogram due to fetal arrhythmia. The fetal echocardiogram showed two small echogenic, RV apex and septal masses, suspicious of rhabdomyomas. After a routine pregnancy and a normal spontaneous vaginal delivery (39 weeks 1 day), the male baby was admitted to the neonatal intensive care unit for further monitoring and postnatal evaluation.
CONCLUSIONS
Rhabdomyomas are extremely rare and unique tumors. These tumors are very dangerous, but they usually regress after birth. During the prenatal period, early cardiac tumor detection provides important information about fetal wellbeing, delivery planning, and necessary postnatal care. We present this case to share our findings with our pediatric colleagues. Although a rarely reported case, we hope this cardiac rhabdomyoma case report and literature review can increase cardiac tumor awareness.
Topics: Adult; Child; Female; Fetal Diseases; Heart Neoplasms; Humans; Infant; Infant, Newborn; Male; Pregnancy; Rhabdomyoma; Tuberous Sclerosis; Ultrasonography, Prenatal
PubMed: 35449076
DOI: 10.1186/s13256-022-03371-1