Key result
Novel de novo FHL2 variant linked to refractory infantile dilated cardiomyopathy with persistent ~16% LVEF.
Why the study?
FHL2 variants are associated with early-onset severe dilated cardiomyopathy, but such reports remain rare and clinical differentiation from primary endocardial fibroelastosis is important.
Case Report (n=1)
No
This case highlights a rare FHL2 genetic variant associated with severe early-onset infantile dilated cardiomyopathy, suggesting that concurrent endocardial thickening may be a secondary hemodynamic change rather than primary endocardial fibroelastosis.
Background FHL2 is critical for cardiac development, and its variants are associated with early-onset severe dilated cardiomyopathy (DCM), though such reports remain rare. Case presentation The patient was a 30-day-old male infant admitted with a 3-day history of cough, a 2-day history of poor feeding, and lethargy lasting half a day. Echocardiography revealed left ventricular enlargement, with a minimum left ventricular ejection fraction (LVEF) of only 13%, and endocardial thickening. Genetic testing identified a heterozygous missense variant c.391C>T (p.Arg131Cys) in FHL2 . This variant was confirmed to be de novo . According to the American College of Medical Genetics and Genomics (ACMG) guidelines, it was classified as likely pathogenic, suggestive of DCM. After heart failure management and other symptomatic treatments, the patient’s clinical symptoms improved. However, LVEF remained low at 15.5% during the 6-month follow-up. Conclusion The heterozygous missense variant c.391C>T (p.Arg131Cys) in FHL2 is associated with DCM in this patient, and the endocardial thickening may represent a secondary change. However, we acknowledge that without pathological examination of the explanted heart or endomyocardial biopsy, the possibility of primary endocardial fibroelastosis (EFE) cannot be completely excluded. This study emphasizes the clinical importance of distinguishing true primary EFE from secondary EFE-like endocardial changes associated with severe DCM, and genetic testing is valuable for their differential diagnosis.
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Wang et al. (2026) conducted a case report in Dilated cardiomyopathy (DCM) (n=1). Heterozygous missense variant c.391C>T (p.Arg131Cys) in FHL2 was evaluated on Left ventricular ejection fraction (LVEF) and clinical improvement at 6 months. A de novo heterozygous missense variant c.391C>T in FHL2 was identified in an infant with severe dilated cardiomyopathy, with LVEF remaining severely impaired at 15.5% despite 6 months of medical therapy.
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