High yield of LMNA mutations in patients with dilated cardiomyopathy and/or conduction disease referred to cardiogenetics outpatient clinics

Cardiolaminopathies from bench to bedside: challenges in clinical decision-making with focus on arrhythmia-related outcomes

“…In this series of patients, who were implanted with a defibrillator in 59% of cases, male sex, non-missense mutations, and left ventricular dysfunction were associated with development of sustained ventricular tachyarrhythmias, while no relationship was found with the mode of presentation (with isolated or combination of clinical features) [24]. These findings are in line with a previous multicentre study, where a series of risk factors emerged as predictors of the occurrence of ventricular tachyarrhythmias (male gender, non- sustained ventricular tachycardia, left ventricular ejection fraction <45% and non-missense mutation), thus providing an important clinical guide for the decision to implant an ICD [53] (Table 2) [4,6,23,24,27,43,44,47,51–62]…”

“…The same study [42] found a higher thrombin generation in lamin A/C carriers and an altered platelet function suggesting an associated prothrombotic state that may explain the previous findings, as well as the observations of van Tintelen et al [43] of a high risk of thromboembolism in specific families, regardless of identifiable risk factors for thromboembolism and of atrial tachyarrhythmias. Further research is needed in this field.…”

“…A detailed review of all the literature published on the risk of ventricular tachyarrhythmias, and on device activations in carriers of an implantable cardioverter defibrillators (ICDs) are shown in Table 2, in relationship to the series of patients with laminopathies reported in Table 1 [4,6,23,24,27,43,44,47,51–62]. In the largest observational study, reported by Kumar et al [24], the cumulative occurrence of sustained ventricular tachyarrhythmias was 34% at 7 years, and among patients with no history of ventricular tachyarrhythmias the incidence was 22% during a 7-year follow-up.…”

Phenotypic diversity in patients with lipodystrophy associated with LMNA mutations

“…Previous reports show that men with FPLD have lower prevalence of metabolic complications of insulin resistance than women (24,27). He was found to carry a heterozygous substitution in a highly conserved residue localized in exon 6 (p.R349W), which affects the a-helical rod domain of both lamin A and lamin C. This variant was previously reported in a patient with partial lipodystrophy, mild myopathy, and dilated cardiomyopathy (28). There are other previous reports of LMNA amino-terminal head and a-helical rod domain mutations causing overlapping phenotype of partial lipodystrophy and cardiomyopathy or cardiac conduction defects (29,30).…”

Clinical utility gene card for: Dilated Cardiomyopathy (CMD)

“…8 LMNA mutations are also frequently detected in up to 6% of cases and in particular in the subgroup of idiopathic DCM associated with conduction disease (30-33%). 9,10 In certain populations, specific mutations may be overrepresented due to a common founder mutation, for example, the LMNA p.Ser143Pro in 7% of the Finnish idiopathic DCM population or the PLN p.Arg14del in up to 15% of Dutch idiopathic DCM patients. 11,12 Several studies have reported that DCM patients carrying more than one disease-associated mutation have an early onset, severe disease expression and a bad prognosis, which is most likely due to a gene-dosage effect.…”