Unusual adult-onset cardiac rhabdomyomas in tuberous sclerosis complex: a case report.

Background: Tuberous sclerosis complex is a genetic neurocutaneous autosomal dominant syndrome, characterized by the development of multiple benign tumors (hamartomas) affecting various systems. Heart-benign tumors that result from the complex are called cardiac rhabdomyomas. Unlike hamartomas that occur in other organs, cardiac rhabdomyomas are most prevalent in infants and very young children with tuberous sclerosis complex. We present a case of a young adult with tuberous sclerosis who had an unusually late diagnosis of cardiac rhabdomyomas. Case report: A 22-year-old male patient of Afro-descendant, diagnosed with tuberous sclerosis complex in childhood, presented with refractory epilepsy and was treated only with lacosamide. The patient came to medical consultation due to a recent history of episodic, persistent chest pain in the sternal region, associated with physical effort. Echocardiography revealed a non-dilated left ventricle, with several rounded masses of high echogenicity without pedicles at the apical level, the largest measuring 14 × 11 mm, consistent with cardiac rhabdomyomas. Conclusion: Cardiac rhabdomyomas rarely develop in adulthood for individuals with tuberous sclerosis. These late-onset cases can exhibit various symptoms, from simple to complex presentations. Regular clinical checkups are essential for adults with tuberous sclerosis complex.

Perinatal unusual rhabdomyoma location - case report and systematic reviews of the literature.

Objective: To report a case of prenatal diagnosis of cardiac rhabdomyoma (CR) and neonatal surgical treatment as well as undertaking a systematic review of the literature to determine most frequent localization of CR, common signs and symptoms, associated pathologies, incidence of surgery, and prognoses for CR.Methods: We conducted systematic review of the literature on CR that were diagnosed and treated in the perinatal period, searching for English language articles in the PubMed/Medline database that were published within the past 20 years, using the following search terms: "cardiac rhabdomyoma"; "neonates"; "newborn"; "surgery".Results: Eighty-two studies were selected, but only 46 studies met the inclusion criteria. After birth, the majority of newborns were asymptomatic; however, murmurs and arrhythmia were also the two most prevalent signs of CR. The most prevalent location was the ventricles, corresponding to 40.3% of all cases, with 53% of these having a rhabdomyoma in the left ventricle. The incidence of multiple tumors was 56%, and in those cases the location of tumors was also most common in the ventricles. Tuberous sclerosis was the most commonly associated pathology, being present in 72% of cases of CR. Surgical treatment occurred in 27% of cases, and 3% of cases required surgery and prostaglandin. Regarding the perinatal outcome, 6% of cases resulted in fetal or neonatal death.Conclusion: CR are benign tumors which tend to spontaneously regress during early childhood but may have unfavorable outcomes in the presence of obstructive lesions and arrhythmias. Surgery is generally necessary in symptomatic patients.

Complejo esclerosis tuberosa: Reporte de un caso clínico neonatal

RESUMEN El complejo de esclerosis tuberosa es una afección genética, aproximadamente dos tercios de los casos ocurren esporádicamente; se caracteriza por lesiones y tumores benignos (hamartomas) en múltiples sistemas orgánicos. La detección prenatal precisa es importante para el pronóstico, una decisión sobre el resultado del embarazo y el asesoramiento. Se reporta el caso de una gestante sana y su feto con diagnóstico presuntivo de esclerosis tuberosa, por hallazgo de masas intracardiacas en ecografía prenatal, confirmados luego del nacimiento, con afectación de otros órganos, cumpliendo con criterios mayores de diagnóstico. El caso presentado es el primero registrado en el Departamento de Neonatología y tiene el objetivo de mostrar la aproximación diagnóstica prenatal y postnatal de una enfermedad relativamente rara.

ABSTRACT Tuberous sclerosis complex is a genetic condition caused by mutations in the tumor suppressor genes TSC1 and TSC2, located on chromosomes 9 and 16 respectively. Approximately two-thirds of cases occur sporadically and the overall incidence has been estimated to be 1 in 5,800 live births. It is characterized by benign lesions and tumors (hamartomas) in multiple organ systems (brain, heart, skin, eyes, kidneys, lungs, liver). Accurate prenatal detection is important for prognosis, a decision about the pregnancy outcome, and counseling. We report the case of a healthy pregnant woman and her fetus with a presumptive diagnosis of tuberous sclerosis, due to the finding of intracardiac masses on prenatal ultrasound, confirmed after birth, with involvement of other organs, fulfilling the major diagnostic criteria. The case presented is the first recorded case at our Department of Neonatology and this report illustrates the prenatal and postnatal diagnostic approach of a relatively rare disease.

Everolimus for cardiac rhabdomyomas in children with tuberous sclerosis. The ORACLE study protocol (everOlimus for caRdiac rhAbdomyomas in tuberous sCLErosis): a randomised, multicentre, placebo-controlled, double-blind phase II trial.

INTRODUCTION: Tuberous sclerosis complex is a rare genetic disorder leading to the growth of hamartomas in multiple organs, including cardiac rhabdomyomas. Children with symptomatic cardiac rhabdomyoma require frequent admissions to intensive care units, have major complications, namely, arrhythmias, cardiac outflow tract obstruction and heart failure, affecting the quality of life and taking on high healthcare cost. Currently, there is no standard pharmacological treatment for this condition, and the management includes a conservative approach and supportive care. Everolimus has shown positive effects on subependymal giant cell astrocytomas, renal angiomyolipoma and refractory seizures associated with tuberous sclerosis complex. However, evidence supporting efficacy in symptomatic cardiac rhabdomyoma is limited to case reports. The ORACLE trial is the first randomised clinical trial assessing the efficacy of everolimus as a specific therapy for symptomatic cardiac rhabdomyoma. METHODS: ORACLE is a phase II, prospective, randomised, placebo-controlled, double-blind, multicentre protocol trial. A total of 40 children with symptomatic cardiac rhabdomyoma secondary to tuberous sclerosis complex will be randomised to receive oral everolimus or placebo for 3 months. The primary outcome is 50% or more reduction in the tumour size related to baseline. As secondary outcomes we include the presence of arrhythmias, pericardial effusion, intracardiac obstruction, adverse events, progression of tumour reduction and effect on heart failure. CONCLUSIONS: ORACLE protocol addresses a relevant unmet need in children with tuberous sclerosis complex and cardiac rhabdomyoma. The results of the trial will potentially support the first evidence-based therapy for this condition.