Clinical Outcome in KLHL24 Cardiomyopathy

Pathogenic variants in Kelch-like family member 24 ( as a new cause for skin fragility KLHL24; NM_017644.3) were recently identified and cardiomyopathy. KLHL24 is part of a ubiquitin-ligase complex and mediates substrate recognition of intermediate filaments for proteasomal degradation (ie, keratins,1,2 vimentin,2 and desmin3,4). Several studies have shown that patients with heterozygous gain-of-function variants (HET-GOF), typically born with epidermolysis bullosa simplex,1,2 can develop dilated cardiomyopathy (DCM) with desmin-deficiency.3 Meanwhile, hypertrophic cardiomyopathy (HCM) with desmin-overload has been determined in patients with homozygous loss-of-function variants (HOM-LOF).4 This meta-analysis aims to summarize the findings of previous patient studies to determine the clinical outcome in KLHL24 cardiomyopathy.