Treatment of Cardiac Rhabdomyomas with mTOR Inhibitors in Children with Tuberous Sclerosis Complex—A Systematic Review

Sugalska, Monika; Tomik, Anna; Jóźwiak, Sergiusz; Werner, Bożena

doi:10.3390/ijerph18094907

Cited by 31 publications

(27 citation statements)

References 58 publications

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“…Despite the generally favorable outcomes and spontaneous regression, multiple or large cRHMs may result in heart failure or cardiac arrhythmias that require intervention. A meta-analysis summarized the use of mTOR inhibitors in the treatment of cRHM in pediatric patients, most of which were neonates [ 7 ]. It reported that the clinical symptoms improved in 90.9% of patients after treatment and the size of cRHM was reduced by 95.1%.…”

Section: Mtor Inhibitors In the Treatment Of Tscmentioning

confidence: 99%

“…Cardiac rhabdomyoma (cRHM) is a common benign cardiac tumor in patients with TSC that is found in 90% of intrauterine fetuses; Unlike other TSC symptoms, most cRHMs subside spontaneously in early childhood [ 3 ]. However, it may also re-grow or occur de novo in adolescence, especially in girls [ 7 ]. Generally, approximately 20% adults still carried cRHM.…”

Section: Introductionmentioning

confidence: 99%

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Perfect match: mTOR inhibitors and tuberous sclerosis complex

Luo

Shi

et al. 2022

Orphanet J Rare Dis

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Tuberous sclerosis complex (TSC) is an autosomal dominant syndrome that presents with diverse and complex clinical features and involves multiple human systems. TSC-related neurological abnormalities and organ dysfunction greatly affect the quality of life and can even result in death in patients with TSC. It is widely accepted that most TSC-related clinical manifestations are associated with hyperactivation of the mammalian target of rapamycin (mTOR) pathway caused by loss‑of‑function mutations in TSC1 or TSC2. Remarkable progress in basic and translational research has led to encouraging clinical advances. Although mTOR inhibitors (rapamycin/everolimus) demonstrate great potential in TSC management, two major concerns hamper their generalized application. One is the frequent manifestation of adverse events, such as stomatitis, infections, and menstrual disorders; and the other is the poor response in certain patients. Thus, indicators are required to effectively predict the efficacy of mTOR inhibitors. Herein, we have summarized the current utilization of mTOR inhibitors in the treatment of TSC and focused on their efficacy and safety, in an attempt to provide a reference to guide the treatment of TSC.

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Section: Mtor Inhibitors In the Treatment Of Tscmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Perfect match: mTOR inhibitors and tuberous sclerosis complex

Luo

Shi

et al. 2022

Orphanet J Rare Dis

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“…Currently, there is no approved pharmacological treatment for this condition, and cardiac surgery is the usual treatment for severe symptomatic patients. 45 , 46 The upcoming randomized trial assessing the efficacy of everolimus as a specific therapy for symptomatic cardiac rhabdomyoma (ORACLE) will potentially support the first evidence-based therapy for this condition. 46 , 47 …”

Section: Clinical Features and Their Managementmentioning

confidence: 99%

“… 45 , 46 The upcoming randomized trial assessing the efficacy of everolimus as a specific therapy for symptomatic cardiac rhabdomyoma (ORACLE) will potentially support the first evidence-based therapy for this condition. 46 , 47 …”

Section: Clinical Features and Their Managementmentioning

confidence: 99%

Monitoring and Managing Patients with Tuberous Sclerosis Complex: Current State of Knowledge

Gomes¹,

Jesus‐Ribeiro²,

Palavra³

2022

JMDH

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Tuberous sclerosis complex (TSC) is a rare genetic disease of autosomal dominant transmission that, in most cases, results from the presence of pathogenic variants of the TSC1 or TSC2 genes, encoding hamartin and tuberin, respectively. It is a multisystemic disease, affecting most frequently the brain, skin, kidney, and heart. The wide variety of possible clinical manifestations, given this multisystem dimension, makes the follow-up of patients with TSC an exercise of multidisciplinarity. In fact, these patients may require the intervention of various medical specialties, which thus have to combine their efforts to practice a medicine that is truly holistic. The past few years have witnessed a dramatic leap not only in the diagnosis and management of TSC patients, with standard monitoring recommendations, but also in the therapeutic field, with the use of mTORC1 inhibitors. In this article, we review the clinical manifestations associated with TSC, as well as the treatment and follow-up strategies that should be implemented, from a multidisciplinary perspective.

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“…The effectiveness of oral mTOR inhibitors for the treatment of TSC-related manifestations is established for subependymal giant cell astrocytoma (SEGA), renal angiomyolipoma, lymphangioleiomyomatosis (LAM), epilepsy, cardiac rhabdomyoma, and skin lesions [10][11][12][13][14][15]. However, oral mTOR inhibitors are not approved by regulators for treatment of facial angiofibroma as there could be increased risk of systemic side effects associated with an immunosuppressive effect of these drugs.…”

Section: Introductionmentioning

confidence: 99%

Characterization and management of facial angiofibroma related to tuberous sclerosis complex in the United States: retrospective analysis of the natural history database

Boggarapu¹,

Roberds

Nakagawa

et al. 2022

Orphanet J Rare Dis

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Background Facial angiofibroma is the most predominant cutaneous manifestation of tuberous sclerosis complex (TSC), a rare autosomal dominant genetic disorder impacting the mechanistic target of rapamycin (mTOR). Facial angiofibroma can bleed spontaneously, impair eyesight, and cause aesthetic disfiguration causing psychological and social stress. To date, there is little or no evidence on the demographics, and other TSC features associated with facial angiofibroma or the use of mTOR inhibitor for the management of facial angiofibroma. This is a retrospective study of TSC Alliance’s Natural History Database aimed to characterize facial angiofibroma and to evaluate features associated with a higher risk of facial angiofibroma or the use of topical mTOR inhibitors for the management of facial angiofibroma. Data in the NHD was obtained from 18 clinical sites in the US since 2006. Results Of the 2240 patients, 2088 patients were enrolled in the US and data from 2057 patients were included in this analysis. The mean (median) age of overall TSC patients was 22.4 (19.0) years. A total of 69 patients were ≤ 5 years of age. Facial angiofibroma was noted in 1329 (64.6%) patients with TSC. Patients with facial angiofibroma were older on average (Mean: 25.9 [median, 23.0] vs. 16.0 [12.4 years] years, p < 0.0001). In patients with vs. without facial angiofibroma, TSC2 mutation (38.9% vs. 34.8%) was more common than TSC1 mutation (12.3% vs. 18.1%), and the incidence rate of most of the other TSC-related manifestations was significantly higher in patients with facial angiofibroma. Majority of patients had focal seizures (72.8% vs. 60.7%), followed by angiomyolipoma (63.7% vs. 21.8%) and renal cysts (59.4% vs. 33.5%). The age groups, 11–17 (odds ratio [OR], 2.53) and 18–45 years (5.98), TSC2 mutation (1.31), focal seizures (1.50), ADHD (1.47) angiomyolipoma (2.79), and renal cysts (2.63) were significantly associated with a higher risk of facial angiofibroma based on multivariate logistic regression. Abrasive or laser therapy was used by 17.1% and 2.6% patients, respectively. Topical mTOR inhibitor use was noted for 329 (24.8%) patients with facial angiofibroma. Overall systemic mTOR inhibitor use was observed in 399 (30.0%) patients for management of one or more TSC manifestations. Use of systemic mTOR inhibitor for facial angiofibroma was noted for 163 (12.3%) patients, among whom only 9 (0.7%) patients used exclusively for the management of facial angiofibroma. Of the patients with facial angiofibroma, 44.6% did not receive any treatment. Significantly higher use of topical mTOR inhibitor was associated with the 11–17 years age group (OR, 1.67), anxiety (1.57), angiomyolipoma (1.51), and renal cysts (1.33). Conclusions The presence of TSC2 mutations and most other TSC-related manifestations was significantly higher in patients with facial angiofibroma. About one-fourth of patients with facial angiofibroma used a topical mTOR inhibitor and use of systemic mTOR inhibitor for the management of facial angiofibroma or for the other manifestations was noted for 30.0%. About 44.6% of patients did not receive any treatment for the management of facial angiofibroma.

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Treatment of Cardiac Rhabdomyomas with mTOR Inhibitors in Children with Tuberous Sclerosis Complex—A Systematic Review

Cited by 31 publications

References 58 publications

Perfect match: mTOR inhibitors and tuberous sclerosis complex

Perfect match: mTOR inhibitors and tuberous sclerosis complex

Monitoring and Managing Patients with Tuberous Sclerosis Complex: Current State of Knowledge

Characterization and management of facial angiofibroma related to tuberous sclerosis complex in the United States: retrospective analysis of the natural history database

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