Novel FKTN p. Gly424Asp variant associated with adult-onset dilated cardiomyopathy and seizures in a Chinese patient

Abstract

Fukuyama congenital muscular dystrophy (FCMD) is a rare autosomal recessive α-dystroglycanopathy typically presenting in infancy with severe hypotonia, intellectual disability, and cortical malformations. Adult-onset phenotypes are uncommon and usually dominated by isolated cardiomyopathy without neurological involvement. We report the first genetically confirmed case of adult-onset FKTN-related dilated cardiomyopathy (DCM) in a Chinese patient harboring a novel homozygous FKTN missense mutation. We present here a 31-year-old man presented with acute heart failure secondary to dilated cardiomyopathy and subsequently developed a generalized tonic–clonic seizure. Neurological examination revealed mild bilateral gastrocnemius atrophy without weakness, preserved cognition, and normal deep tendon reflexes. Serum creatine kinase was markedly elevated (>7,000 U/L). Echocardiography and cardiac MRI confirmed DCM with non-compaction features. Brain MRI was unremarkable. Genetic testing identified a novel homozygous FKTN mutation (c. 1271G>A, p. Gly424Asp). Following treatment with heart failure medication and prophylactic levetiracetam, cardiac function improved, and the patient remained seizure-free during a 12-month follow-up.

Conclusions: This case expands the phenotypic spectrum of FKTN-related disorders to include adult- onset DCM accompanied by seizures. While the exact mechanism remains to be fully elucidated, the presence of seizures in the absence of cortical malformations highlights a potential functional neurological involvement. Targeted FKTN screening is recommended for adults with unexplained cardiomyopathy and markedly elevated CK.