Abstract 16713: Desmin-Related Myopathy: A Meta-analysis Of All Reported Heterozygous DES Mutation Carriers
Desmin-related myopathy is an inherited skeletal and cardiac myopathy mainly caused by desmin gene (DES) mutations. Interpretation of DES related phenotype is hampered by many publications on small numbers of patients and by the fact that several patients have repeatedly been described. In order to put DESrelated phenotype into perspective, we performed a meta-analysis of all reported DESmutation carriers.
Methods: We performed a PubMed search for publications on heterozygous DES mutation carriers published from 1998 to April 2010. Patients described in different studies were included only once.
Results: In total, 197 DES mutation carriers were identified. Of these, 36 patients were described more than once. We therefore included 161 patients (41 different mutations). Both neurological and cardiological signs were present in 48% of carriers, whereas isolated neurological and isolated cardiological signs were present in 22% and 23%, respectively. More than 70% of carriers exhibited myopathy or muscular weakness. Up to 50% had cardiomyopathy of which dilated cardiomyopathy was most prevalent (18%). In 62% cardiac conduction disease (CCD) and/or arrhythmias were reported of which atrioventricular block was most prevalent (36%). Two-thirds of the cases with CCD and/or arrhythmias also had cardiomyopathy. Symptoms started at a mean age of 35 yrs (11-72). A quarter of carriers had died at a mean age of 49 yrs (28-62). Sudden cardiac death occurred in two patients with a pacemaker, suggesting a ventricular tachyarrhythmia as cause of death. More than half of the mutations were located in the 2B domain. Mutations in the 2B domain were predominant in patients with an isolated neurological phenotype (28/31; 90%), whereas head and tail domain mutations were predominant in patients with an isolated cardiological phenotype (24/36; 67%).
Conclusions: The majority of DES mutation carriers demonstrate cardiological signs (75%) particularly CCD and (dilated) cardiomyopathy; nearly a quarter of carriers exhibit an isolated cardiological phenotype. Although recognition of DES related phenotype can be difficult due to clinical variability, it is important to recognize it because early detection of the cardiac phenotype and subsequent treatment can be life-saving.
- © 2010 by American Heart Association, Inc.