Idiopathic Restrictive Cardiomyopathy in Children and Young Adults

Anderson, Heather N.; Cetta, Frank; Driscoll, David J.; Olson, Timothy M.; Ackerman, Michael J.; Johnson, Jonathan N.

doi:10.1016/j.amjcard.2018.01.045

Cited by 35 publications

(23 citation statements)

References 12 publications

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“…Individuals with a P/LP variant associated with RCM were more likely to have a de novo variant (80%) compared to those with HCM or DCM (9 and 20% of those with a P/LP variant, respectively). This is not unexpected given historically poor survival associated with pediatric RCM, effectively reducing the childbearing population (Anderson et al, ). The high rate of de novo variants in this group is in line with rates observed in other genetic conditions with reduced reproductive fitness.…”

Section: Discussionmentioning

confidence: 90%

“…Outcomes in pediatric cardiomyopathy are extremely variable and differ between cardiomyopathy phenotype and underlying etiology (Lee et al, ). Historically, RCM has been associated with poor survival in pediatric patients (Anderson et al, ). It is unclear if de novo variation in pediatric cardiomyopathy may be associated with worse clinical outcomes.…”

Section: Introductionmentioning

confidence: 99%

“…These variants are typically inherited in an autosomal dominant manner and are observed with significant clinical variability and reduced penetrance. De novo variants have been reported in individuals with cardiomyopathy, largely as single case reports (Anderson et al, 2018;Kaski et al, 2008;Mogensen, Hey, & Lambrecht, 2015;Mouton et al, 2015;Okada et al, 2014;Olson et al, 2000). A few studies have reported frequencies of de novo variation in separate cohorts.…”

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confidence: 99%

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Investigation of de novo variation in pediatric cardiomyopathy

Parrott

Khoury

Shikany

et al. 2020

American J of Med Genetics Pt C

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Pediatric cardiomyopathies can be caused by variants in genes encoding the sarcomere and cytoskeleton in cardiomyocytes. Variants are typically inherited in an autosomal dominant manner with variable expressivity. De novo variants have been reported, however their overall frequency is largely unknown. We sought to determine the rate of de novo, pathogenic and likely pathogenic (P/LP) variants in children with a diagnosis of hypertrophic, dilated, or restrictive cardiomyopathy (HCM, DCM, or RCM), and to compare disease outcomes between individuals with and without a de novo variant. A retrospective record review identified 126 individuals with HCM (55%), DCM (37%), or RCM (8%) ≤18 years of age who had genetic testing. Overall, 50 (40%) had positive genetic testing and 18% of P/LP variants occurred de novo. The rate of de novo variation in those with RCM (80%) was higher than in those with HCM (9%) or DCM (20%). There was evidence of germline mosaicism in one family with RCM. Individuals with de novo variants were more likely than those without to have a history of arrhythmia (p = .049), sudden cardiac arrest (p = .024), hospitalization (p = .041), and cardiac transplantation (p = .030). The likelihood of de novo variation and impact on family risk and screening should be integrated into genetic counseling.

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Section: Discussionmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 99%

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confidence: 99%

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Investigation of de novo variation in pediatric cardiomyopathy

Parrott

Khoury

Shikany

et al. 2020

American J of Med Genetics Pt C

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“…The prognosis of young children with RCM is terribly poor, and heart transplantation is the only method for treatment. 1,2 The pathogenesis of cardiomyopathy varies, and to date, numerous causes of RCM have been investigated. The histology of the myocardium in RCM patients is usually non-specific, with mild myocyte hypertrophy and disarray, as well as slight interstitial fibrosis.…”

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confidence: 99%

Cardiac Fibroblasts Play Pathogenic Roles in Idiopathic Restrictive Cardiomyopathy

Tsuru

Ishida

Narita

et al. 2021

Circ J

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Background: Restrictive cardiomyopathy (RCM) is characterized by impaired ventricular relaxation. Although several mutations were reported in some patients, no mutations were identified in cardiomyocyte expressing genes of other patients, indicating that pathological mechanisms underlying RCM could not be determined by cardiomyocytes only. Cardiac fibroblasts (CFs) are a major cell population in the heart; however, the pathological roles of CFs in cardiomyopathy are not fully understood. Methods and Results: This study established 4 primary culture lines of CFs from RCM patients and analyzed their cellular physiology, the effects on the contraction and relaxation ability of healthy cardiomyocytes under co-culture with CFs, and RNA sequencing. Three of four patients had TNNI3 mutations. There were no significant alterations in cell proliferation, apoptosis, migration, activation, and attachment. However, when CFs from RCM patients were co-cultured with healthy cardiomyocytes, the relaxation velocity of cardiomyocytes was significantly impaired both under direct and indirect co-culture conditions. RNA sequencing revealed that gene expression profiles of CFs in RCM were clearly distinct from healthy CFs. The differential expression gene analysis identified that several extracellular matrix components and cytokine expressions were dysregulated in CFs from RCM patients. Conclusions: The comprehensive gene expression patterns were altered in RCM-derived CFs, which deteriorated the relaxation ability of cardiomyocytes. The specific changes in extracellular matrix composition and cytokine secretion from CFs might affect pathological behavior of cardiomyocytes in RCM.

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“…Elevated RA pressures and PH are usually present [8]. In idiopathic RCM, as demonstrated in our case, myocardial biopsy typically demonstrates patchy endocardial and interstitial fibrosis with compensatory myofibril hypertrophy without myofiber disarray, or findings suggestive of a specific infiltrative heart muscle disease [9][10].…”

Section: Discussionmentioning

confidence: 53%

A Novel Case of Idiopathic Restrictive Cardiomyopathy

Ahmed¹,

Safdar²,

Ramani³

2020

Cureus

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Restrictive cardiomyopathy (CM) usually develops and progresses slowly, over a course of years. The rapid development of idiopathic restrictive CM immediately following a liver transplant is unusual. We describe the case of a patient who developed idiopathic restrictive CM fairly rapidly following a liver transplant. It progressed within a few months to the point where the patient required scheduled paracenteses and dialysis. The morphological definition of restrictive CM consists of bi-atrial dilation with non-dilated and non-hypertrophic ventricles. A cardiac biopsy may be needed when the underlying cause is not evident. When a cardiac biopsy is not able to identify a specific cause, then the word "idiopathic" is used to describe the CM.

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Idiopathic Restrictive Cardiomyopathy in Children and Young Adults

Cited by 35 publications

References 12 publications

Investigation of de novo variation in pediatric cardiomyopathy

Investigation of de novo variation in pediatric cardiomyopathy

Cardiac Fibroblasts Play Pathogenic Roles in Idiopathic Restrictive Cardiomyopathy

A Novel Case of Idiopathic Restrictive Cardiomyopathy

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