Endocardial thickening in dilated cardiomyopathy associated with FHL2 variant: a case report

FHL2 is critical for cardiac development, and its variants are associated with early-onset severe dilated cardiomyopathy (DCM), though such reports remain rare.

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.

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.