[Clinical analysis of pediatric restrictive cardiomyopathy associated with FLNC gene variants in 5 children].

Objective: To summarize the clinical phenotypes, genotypes, and treatment outcomes of restrictive cardiomyopathy (RCM) associated with FLNC gene variants in children. Methods: Case series study. The clinical data of 5 pediatric patients with FLNC gene variant-associated RCM who were admitted to the Department of Pediatrics, Peking University First Hospital, from January 2008 to October 2023, including clinical manifestations, laboratory examinations, echocardiographic findings, genetic testing results, as well as treatment and follow-up outcomes was retrospectively analyzed. Results: Among the 5 patients, there were 4 females and 1 male, with the age of onset ranging from 3 to 5 years. Three patients presented with heart failure symptoms as the initial manifestation, 1 patient with recurrent syncope, and 1 patient was diagnosed asymptomatically via family screening. At initial presentation, 4 patients were graded as class Ⅱ and 1 patient as class Ⅰ according to the modified Ross classification for pediatric heart failure. Three patients had concomitant myopathy, manifesting as decreased muscle strength, spinal deformity and other abnormalities. All 5 patients had electrocardiographic manifestations of conduction block to varying degrees, and 1 patient developed atrial flutter during follow-up. Echocardiography revealed an overlapping phenotype of RCM and hypertrophic cardiomyopathy in 2 patients. All genetic variants were located in the rod domain (ROD) of the FLNC gene. In terms of variant types, 4 patients were missense variants and 1 patient was deletion-insertion variant. The primary treatments included diuretics, β-blockers, and angiotensin-converting enzyme inhibitors. One patient underwent heart transplantation, 3 patients remained clinically stable, and 1 patient was lost to follow-up. Conclusions: FLNC-related RCM typically has an early age of onset, is frequently accompanied by myopathy, and may show conduction block on electrocardiography. Missense variants in the ROD are the predominant type of FLNC gene variant in this disease. Thus, early genetic screening and long-term multidisciplinary follow-up are warranted for affected patients.