Restrictive cardiomyopathy (RCM) is the rarest form of cardiomyopathy, characterized by dilated atria, increased ventricular stiffness with normal ventricular wall thickness and systolic function. The sudden cardiac death or a life-threatening cardiac event due to ventricular arrhythmias or heart block is common, as is heart failure; death occurs within a few years of diagnosis.
RCM usually has autosomal dominant inheritance, but in rare cases autosomal recessive, X-linked and mitochondrial-transmitted disease also occurs. Most identified genes encode sarcomere or Z-disk proteins, such as TNNI3, TNNT2, MYH7, ACTC1, TPM1, MYL3, and MYL2. Z-disk protein-encoding genes, including MYPN, TTN, BAG3 and FLNC have also been identified. Missense variants in DES have been identified in several families with desmin-related myopathy, which can present with RCM, with or without skeletal myopathy and/or atrioventricular block (PMID:25186923, PMID:26666891).