Cardiac-Predominant Fukutinopathy Caused by Novel Compound Heterozygous FKTN Variants: A Diagnostic and Genetic Odyssey.

Background

Fukutinopathy is a rare autosomal recessive dystroglycanopathy caused by pathogenic FKTN variants. Cardiac-predominant presentations without overt neuromuscular manifestations are uncommon. CASE SUMMARY We report a 30-year-old Indian man with dilated cardiomyopathy, persistent QT prolongation, subepicardial late gadolinium enhancement on cardiac magnetic resonance imaging, and hyperCKemia. Whole-exome sequencing identified compound heterozygous FKTN variants: c.1112A > G (p.Tyr371Cys; likely pathogenic) and c.1224G > T (p.Lys408Asn; variant of uncertain significance). Parental Sanger sequencing confirmed trans inheritance. Genotype-directed evaluation subsequently revealed clinically silent skeletal myopathy. Guideline-directed medical therapy was initiated, and left ventricular systolic function remained stable at 6-month follow-up.

Conclusions

This case expands the cardiac spectrum of Fukutinopathy by demonstrating a cardiac-predominant phenotype with subclinical myopathy. Comprehensive genetic evaluation with segregation analysis should be considered in selected patients with unexplained nonischemic cardiomyopathy, even in the absence of overt neuromuscular features.