Lamin A/C Cardiomyopathy
Cutting Edge to Personalized Medicine
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Dilated cardiomyopathy (DCM) has a prevalence currently estimated as high as 1:250/1:500 and affects mostly young working-age people.1 Despite recent advances in medical and device therapies, the prognosis of DCM has been significantly improved in last decades,2 heart failure or sudden deaths, hospitalizations, need of heart transplantation, and morbidity rates remain relatively high and unpredictable.3 Consequently, more accurate risk stratification is still a critical and unmet issue.
See Article by Nishiuchi et al
Genetic characterization is gaining a prominent role in personalizing DCM prognostication. In the past, the proportion of patients with genetically determined DCM has been substantially underestimated because of variable clinical presentation, incomplete disease penetrance, and the lack of specific phenotypes. However, recent series using genetic screening suggest that ≤40% of DCM is genetically determined.4 To date, >50 genes have been implicated in DCM.5 Nevertheless, genotype–phenotype interactions still represent a challenge for translational research and cardiology. In fact, genotype information often does not have a known corresponding specific clinical phenotype. In particular, the clinical management of relatives carrying likely or possibly pathogenic mutations without overt phenotype remains currently uncertain in the specific setting of DCM.
In this field, LMNA had always represented the more investigated gene with several prospective and retrospective studies.6–8 Because of the association with a relatively high incidence of sudden cardiac death or major ventricular arrhythmias, even before development of systolic left ventricular dysfunction, LMNA mutations represent the only genetic background in DCM that change clinical choices such as the implantable cardioverter defibrillator therapy in …