Sudden death in a 15-year-old with diffuse cardiac rhabdomyomatosis: an autopsy case report

Fuller, Maren Y.; Wolf, Dwayne A.; Buja, L. Maximilian

doi:10.1016/j.carpath.2014.07.004

Cited by 6 publications

(5 citation statements)

References 8 publications

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“…Cardiac rhabdomyomas occur in approximately 60% of the TSC cases, and therefore, in the presence of rhabdomyoma in echocardiography, the patient should be evaluated in terms of TSC. 11 Rhabdomyomas, which are generally detected in the foetal or neonatal period, tend to regress spontaneously in the first few years after birth. 12 Therefore, these masses in the heart do not require medical or surgical treatment, unless they have severe valve regurgitation, life-threatening dysrhythmia, or severe stenosis of the ventricular outflow tract in the early postnatal period.…”

Section: Discussionmentioning

confidence: 99%

“…As a result of haemodynamic instability due to the tumour's location, the risk of sudden death increase in such patients. 11 Surgical intervention is recommended only in the presence of life-threatening refractory dysrhythmia or severe haemodynamic disorder. 13 Therefore, in such cases, no delay must be caused in terms of medical or surgical intervention.…”

Section: Discussionmentioning

confidence: 99%

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Everolimus treatment in a 3-month-old infant with tuberous sclerosis complex cardiac rhabdomyoma, severe left ventricular outflow tract obstruction, and hearing loss

2021

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Tuberous sclerosis complex is a rare multisystem genetic disorder characterised by the growth of numerous tumour-like malformations in many parts of the body including skin, kidneys, brain, lung, eyes, liver, and heart. Mutations in the TSC1 or TSC2 genes have been reported to cause disruption in the TSC1–TSC2 intracellular protein complex, causing over-activation of the mammalian target of rapamycin protein complex. In this study, we present a 3-month-old male infant diagnosed with tuberous sclerosis, bilateral neurosensorial hearing loss, Wolff–Parkinson–White syndrome on electrocardiography, multiple cardiac rhabdomyomas with severe stenosis in the left ventricular outflow tract, who responded well to the Everolimus therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Everolimus treatment in a 3-month-old infant with tuberous sclerosis complex cardiac rhabdomyoma, severe left ventricular outflow tract obstruction, and hearing loss

2021

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“…It can consist of numerous military nodules measuring less than 1 mm. In this instance the term "rhabdomyomatosis" has been used [14,15] Tumor cells do not express cell proliferation markers such as Ki-67 and PCNA, indicating that the lesions are more likely to be hamartomas than neoplasms [13].…”

Section: Discussionmentioning

confidence: 99%

“…In one study, of 103 primary cardiac tumors causing sudden death, 9 cases (8.7%) were rhabdomyoma [27]. Diffuse cardiac rhabdomyomatosis with or without compensatory hypertrophy was reported in some other sudden death cases [14,15]. Nonobstructive cardiac rhabdomyoma can also progress to cause right ventricular outflow tract obstruction [28].…”

Section: Discussionmentioning

confidence: 99%

Autopsy case of right ventricular rhabdomyoma in tuberous sclerosis complex

et al. 2019

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Tuberous sclerosis complex (TSC) is a genetic multisystem disorder characterized by widespread hamartomas in several organs, including the brain, heart, skin, eyes, kidney, lung, and liver. Rhabdomyoma is the most common cardiac tumor diagnosed in fetuses, neonates and infants, and is closely linked to TSC. Here we describe an autopsy case of right ventricular rhabdomyoma in TSC. The deceased was a 3-month-old male infant, and TSC with a cardiac tumor had been diagnosed before his death. Since the cardiac tumor had not been physically blocking the blood flow, he had not undergone surgical intervention. At autopsy, the patient's height was 62 cm and his body weight was 6 kg. The heart weighed 37.3 g and the right ventricle was filled with the tumor. The tumor measured 2.1cm × 1.6cm, being a fusion of multiple tumors with several attachment sites to the myocardium. Histologically, the tumor was diagnosed as a rhabdomyoma, and was positive for mammalian target of rapamycin (mTOR). The brain weighed 795.0 g, without hydrocephalus. The cut surface of the brain revealed multiple cortical tubers and subependymal nodules. Through screening for the TSC1 (hamartin) and TSC2 (tuberin) genes, a nonsense mutation, c.1108C>T:p.Gln370*, was detected in the TSC2 gene. Immediate cause of death was determined to be ventricular obstruction by a cardiac rhabdomyoma with insidious growth. This case highlights the need for forensic pathologists to perform a complete autopsy to determine the cause of sudden death with cardiac tumor, including genetic examination.

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“…New techniques allow the discovery of mitochondrial networks, whose function is maintained by three processes, including 1) mitochondrial biogenesis (increase in mitochondrial number); 2) mitophagy; and 3) continuous mitochondrial fission (division) and fusion 2, 3 . Impaired mitochondrial biogenesis is a feature of myocardial hypertrophy and end-stage ischemic heart failure in humans 4 , while autophagy has been central to defects in human heart failure 5, 6 . Evidence of altered mitochondrial dynamics (fission and fusion) in human heart failure, specifically in idiopathic dilated cardiomyopathy, has recently been reported 7 .…”

Section: Introductionmentioning

confidence: 99%

BRG1 and BRM SWI/SNF ATPases redundantly maintain cardiomyocyte homeostasis by regulating cardiomyocyte mitophagy and mitochondrial dynamics in vivo

Bultman

Holley

Ridder

et al. 2016

Cardiovascular Pathology

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There has been an increasing recognition that mitochondrial perturbations play a central role in human heart failure. Discovery of mitochondrial networks, whose function is to maintain the regulation of mitochondrial biogenesis, autophagy (‘mitophagy’) and mitochondrial fusion/fission, are new potential therapeutic targets. Yet our understanding of how the molecular underpinning of these processes is just emerging. We recently identified a role of the SWI/SNF ATP-dependent chromatin remodeling complexes in the metabolic homeostasis of the adult cardiomyocyte using cardiomyocyte-specific and inducible deletion of the SWI/SNF ATPases BRG1 and BRM in adult mice (Brg1/Brm double mutant mice). To build upon these observations in early alterated metabolism, the present study looks at the subsequent alterations in mitochondrial quality control mechanisms in the impaired adult cardiomyocyte. We identified that Brg1/Brm double-mutant mice exhibited an increased mitochondrial biogenesis, increases in ‘mitophagy’, and alterations in mitochondrial fission and fusion that led to small, fragmented mitochondria. Mechanistically, increases in the autophagy and mitophagy-regulated proteins Beclin1 and Bnip3 were identified, paralleling changes seen in human heart failure. Cardiac mitochondrial dynamics were perturbed including decreased mitochondria size, reduced number, and altered expression of genes regulating fusion (Mfn1, Opa1) and fission (Drp1). We also identified cardiac protein amyloid accumulation (aggregated fibrils) during disease progression along with an increase in pre-amyloid oligomers and an upregulated unfolded protein response including increased GRP78, CHOP, and IRE-1 signaling. Together, these findings described a role for BRG1 and BRM in mitochondrial quality control, by regulating mitochondrial number, mitophagy, and mitochondrial dynamics not previously recognized in the adult cardiomyocyte. As epigenetic mechanisms are critical to the pathogenesis of heart failure, these novel pathways identified indicate that SWI/SNF chromatin remodeling functions are closely linked to mitochondrial quality control mechanisms.

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Sudden death in a 15-year-old with diffuse cardiac rhabdomyomatosis: an autopsy case report

Cited by 6 publications

References 8 publications

Everolimus treatment in a 3-month-old infant with tuberous sclerosis complex cardiac rhabdomyoma, severe left ventricular outflow tract obstruction, and hearing loss

Everolimus treatment in a 3-month-old infant with tuberous sclerosis complex cardiac rhabdomyoma, severe left ventricular outflow tract obstruction, and hearing loss

Autopsy case of right ventricular rhabdomyoma in tuberous sclerosis complex

BRG1 and BRM SWI/SNF ATPases redundantly maintain cardiomyocyte homeostasis by regulating cardiomyocyte mitophagy and mitochondrial dynamics in vivo

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