Presentation Information
[II-TKIS-P-9]Severe Fetal-Onset Biventricular Non-Compaction Cardiomyopathy caused by a De Novo Heterozygous ACTN2 Variant
○Hiroshi Yamanaka, Ayako Nagai, Hirokuni Yamazawa, Daisuke Sasaki, Yuto Suzuki, Atsuhito Takeda (Pediatric Department, Hokkaido University, Hokkaido, Japan)
Keywords:
non-compaction of the ventricular myocardium,α-actinin 2 protein,prenatal diagnosis
Background Non-compaction cardiomyopathy (NCCM) has variable clinical severity. While several causative genes for left ventricular NCCM are known, the genetic etiology of biventricular NCCM remains poorly understood. We report a case of severe, fetal-onset biventricular NCCM caused by a de novo heterozygous variant in the ACTN2 gene. Case Presentation A 1-year-old female was suspected of biventricular NCCM with reduced systolic function of GA 38 weeks. From birth, she required mechanical ventilation and continuous intravenous inotropic support for severe heart failure. Enteral feeding intolerance and vomiting initially suggested metabolic or mitochondrial disorders. However, whole exome sequencing identified a de novo heterozygous ACTN2 variant (c.119A>T:p.Gln40Leu), classified as Likely Pathogenic per ACMG criteria. The genetic diagnosis established sarcomeric cardiomyopathy etiology, enabling de-escalation of metabolic differentials. Optimized enteral with ongoing intensive heart failure therapy stabilized her cardiac status, facilitating progression toward heart transplantation candidacy. Conclusion The ACTN2 gene encodes α-actinin, essential for sarcomere stability; mutations cause various cardiomyopathies. The fetal-onset and extreme biventricular severity in this case appear to be unprecedented. This case demonstrates that genetic testing in NCCM can significantly impact clinical management and decision-making. Further research is needed to elucidate how ACTN2 variants lead to such severe biventricular phenotypes.