Emerging Genotype–Phenotype Associations in Dilated Cardiomyopathy

Njoroge, Joyce N.; Mangena, Jennifer C.; Aribeana, Chiaka; Parikh, Victoria N.

doi:10.1007/s11886-022-01727-z

Cited by 11 publications

(10 citation statements)

References 64 publications

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“…Recently, extensive investigations into genotype–phenotype correlations in adult dilated cardiomyopathy have been conducted. 18 Adult dilated cardiomyopathy patients with LMNA variants experienced earlier onsets and worse prognoses compared with other variant types. 19,20 In this study, we demonstrated that pathogenic variants in pediatric RCM patients correlated with worse prognoses.…”

Section: Discussionmentioning

confidence: 99%

Clinical Outcomes and Genetic Analyses of Restrictive Cardiomyopathy in Children

Ishida

Hirose

Ishii

et al. 2023

Circ: Genomic and Precision Medicine

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BACKGROUND: Restrictive cardiomyopathy in children is rare and outcomes are very poor. However, little information is available concerning genotype-outcome correlations. METHODS: We analyzed the clinical characteristics and genetic testing, including whole exome sequencing, of 28 pediatric restrictive cardiomyopathy patients who were diagnosed from 1998 to 2021 at Osaka University Hospital in Japan. RESULTS: The median age at diagnosis (interquartile range) was 6 (2.25–8.5) years. Eighteen patients received heart transplantations and 5 patients were on the waiting list. One patient died while waiting for transplantation. Pathologic or likely-pathogenic variants were identified in 14 of the 28 (50%) patients, including heterozygous TNNI3 missense variants in 8 patients. TNNT2 , MYL2 , and FLNC missense variants were also identified. No significant differences in clinical manifestations and hemodynamic parameters between positive and negative pathogenic variants were detected. However, 2- and 5-year survival rates were significantly lower in patients with pathogenic variants (50% and 22%) compared with survival in patients without pathogenic variants (62% and 54%; P =0.0496, log-rank test). No significant differences were detected in the ratio of patients diagnosed at nationwide school heart disease screening program between positive and negative pathogenic variants. Patients diagnosed by school screening showed better transplant-free survival compared with patients diagnosed by heart failure symptoms ( P =0.0027 in log-rank test). CONCLUSIONS: In this study, 50% of pediatric restrictive cardiomyopathy patients had pathogenic or likely-pathogenic gene variants, and TNNI3 missense variants were the most frequent. Patients with pathogenic variants showed significantly lower transplant-free survival compared with patients without pathogenic variants.

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Section: Discussionmentioning

confidence: 99%

Clinical Outcomes and Genetic Analyses of Restrictive Cardiomyopathy in Children

Ishida

Hirose

Ishii

et al. 2023

Circ: Genomic and Precision Medicine

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“…Heart failure is a clinical syndrome with a high mortality and increased prevalence in populations with cardiovascular risk factors, which are classi ed as acquired pathology and hereditary predisposition. 22 The continual rapid progress of molecular biological techniques over the past two decades and the related increases in choices of different genetic testing methods have led to a dramatic increase in our understanding of the genetic architecture of heart failure. To date, many candidate genes have been attributed to important factors related to the occurrence and development of heart failure, including encoding sarcomeric and cytoskeleton proteins (e.g., TTN, MYH7, and MYBPC3), calcium-handled proteins (e.g., PLN and RYR2), and metabolic enzymes (e.g., GLA and PRKAG2), transmembrane proteins (e.g., LAMP2 and SCN5A), 23 but there are few reports about the relationship between genes involved in immune regulation and cardiomyopathy.…”

Section: Relationship Xiap and Heart Failurementioning

confidence: 99%

Novel XIAP mutation in early-onset Crohn’s disease complicated with Acute Heart Failure: a case report

Peng

Jiang

et al. 2023

Preprint

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Background The X-linked inhibitor of apoptosis (XIAP) protein is encoded by the XIAP gene and is critical for multiple cell responses. XIAP plays a role in preventing cell death.We report the clinical features and results of hemizygous mutation of the XIAP gene in a young male died due to Crohn’s disease complicated with Acute Heart Failure.A young male of 16 years of age died due to no available therapy. Case presentation A young male of 16 years of age was initially diagnosed with Crohn's disease based on evidence from endoscopic and histological findings. Although supporting care, anti-infective drugs and biologics were applied consecutively for 11 months, his clinical manifestations and laboratory indices (patient’s condition) were not improved. This was followed by poor a nutritional status and sustained weight loss. Subsequently, acute heart failure ledto exacerbation of the patient’s condition. Therefore, he was diagnosed with wet beriberi according to thiamine deficiency, but standard medical therapy for heart failure and thiamine supplementation did notreverse the adverse outcomes. Finally, comprehensive genetic analysis of peripheral blood-derived DNA revealed a novel hemizygous mutation of the XIAP gene (c.1259_1262 delACAG), which was inherited from his mother. Conclusion The novel XIAP mutation (c.1259_1262 delACAG) was identified in this study. It may be an important cause of Crohn's disease and plays an important role in the progression of heart failure. Additionally,thiamine deficiency triggers avicious cycle.

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“…In about 66% of the cases, the cause is idiopathic. At times, the disease is an accidental finding and is severely underdiagnosed [4][5][6][7][8][9][10][11][12]. A considerable number of cases happen to be present in children younger than one year of age: 3.8 points per 1 lakh cases every year [13,14].…”

Section: Review Epidemiologymentioning

confidence: 99%

Dilated Cardiomyopathy in Children: Early Detection and Treatment

Mallavarapu¹,

Taksande²

2022

Cureus

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Cardiomyopathy is segregated into primary and secondary categories, leading to different phenotypes, including dilated, hypertrophic, and restrictive patterns. Dilated cardiomyopathy (DCM) is a mixed bag of heart diseases with the unique features of cardiac dilatation and subnormal to poor myocardial contractility. Dilated cardiomyopathy in the pediatric age group is generally characterized by unobstructed, dilated, and contracting left ventricular chamber defects and is associated with heart failure. Other causes include genetic juvenile-onset cardiomyopathy, drug-induced cardiomyopathy, stress-induced cardiomyopathy, hemochromatosis, endocrine causes (thyroid disorder and pheochromocytoma), autoimmune diseases, and nutritional deficiencies (selenium and thiamine). It is characterized by thinning of the left ventricle, a dilated left ventricle or biventricular dilatation, left ventricular systolic dysfunction, left ventricular diastolic dysfunction, global hypokinesia, and cardiomegaly (seen on a chest X-ray). Decreased cardiac output leads to fatigue, cachexia, narrow pulse pressure, dicrotic pulse/hypokinetic pulse, dyspnea, cool extremities, decreased blood supply to the brain (cognitive dysfunction), and reduced blood supply to the kidney (renal failure). Left ventricular diastolic dysfunction can result in dyspnea, orthopnea, and paroxysmal nocturnal dyspnea. Cardiomyopathy can also occur with or without left ventricular dysfunction, as in left ventricular non-compaction cardiomyopathy (LVNC), which is a rare heart disease occurring due to two (likely) pathogenic nonsense mutations: DSG2-p.S363X and TBX20-p.D278X. The study of familial forms of LVNC is helpful for risk prediction and genetic counseling of relatives. Right ventricular chamber failure can be identified on the electrocardiogram as sinus tachycardia and non-specific ST/T changes. The complications include arrhythmia (atrial fibrillation) and thromboembolism (left ventricular mural thrombosis). It is of utmost importance in the field of heart transplantation as the definitive treatment of the disease. Heart transplantation is now an acceptable treatment option for patients with dilated cardiomyopathy. This short review highlights different methods for the detection and diagnosis of dilated cardiomyopathy and the treatment modalities available for the same.

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Emerging Genotype–Phenotype Associations in Dilated Cardiomyopathy

Cited by 11 publications

References 64 publications

Clinical Outcomes and Genetic Analyses of Restrictive Cardiomyopathy in Children

Clinical Outcomes and Genetic Analyses of Restrictive Cardiomyopathy in Children

Novel XIAP mutation in early-onset Crohn’s disease complicated with Acute Heart Failure: a case report

Dilated Cardiomyopathy in Children: Early Detection and Treatment

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