Cardiac and Neuromuscular Features of Patients With<i>LMNA</i>-Related Cardiomyopathy

Peretto, Giovanni; Resta, Chiara Di; Perversi, Jacopo; Forleo, Cinzia; Maggi, Lorenzo; Politano, Luisa; Barison, Andrea; Previtali, Stefano C.; Carboni, Nicola; Brun, Francesca; Pegoraro, Elena; D’Amico, Adele; Rodolico, Carmelo; Magri, Francesca; Manzi, Rosa C.; Palladino, Alberto; Isola, Franco; Gigli, Lorenzo; Mongini, Tiziana; Semplicini, Claudio; Calore, Chiara; Ricci, Giulia; Comi, Giacomo Pietro; Ruggiero, Lucia; Bertini, Enrico; Bonomo, Paolo; Nigro, Gerardo; Resta, Nicoletta; Emdin, Michele; Favale, Stefano; Siciliano, Gabriele; Santoro, Lucio; Sinagra, Gianfranco; Limongelli, Giuseppe; Ambrosi, Alessandro; Ferrari, Maurizio; Golzio, Pier Giorgio; Bella, Paolo Della; Benedetti, Sara; Sala, Simone

doi:10.7326/m18-2768

Cited by 36 publications

(52 citation statements)

References 19 publications

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“…Although the cardiac phenotype was atypical for LMNA cardiomyopathy, the neuromuscular manifestations were similar to those commonly observed in patients with LMNA variants 11 …”

Section: Discussionsupporting

confidence: 57%

“…Genotype-phenotype correlation of LMNA variants involving the Arg541 residue: a case report with multimodality imaging and literature review similar to those commonly observed in patients with LMNA variants. 11 Few case reports have described patients with LMNA cardiomyopathy and missense variants involving the Arg541 residue, and all of them displayed an atypical presentation with many similarities to our case. Kwon and colleagues reported the case of an adolescent girl with the same variant as our patient, who presented with recurrent VT and had severe wall thinning and transmural LGE in the LV apex and lateral wall.…”

Section: Discussionsupporting

confidence: 55%

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Genotype–phenotype correlation of LMNA variants involving the Arg541 residue: a case report with multimodality imaging and literature review

et al. 2020

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We present a case of atypical LMNA cardiomyopathy associated with the pathogenic variant p.Arg541Ser. The patient had early-onset severe ventricular arrhythmias but atrioventricular conduction was normal. Segmental motion abnormalities and a large transmural scar, mainly apical and lateral, were found at cardiac magnetic resonance, corresponding to areas of severe wall thinning at computed tomography and of low voltages at electroanatomic mapping. Ventricular tachycardia ablation was successful in controlling ventricular arrhythmias. Few other cases described patients with pathogenic variants in the Arg541 residue, and they displayed similar atypical features, suggesting a genotype-phenotype correlation which may have specific prognostic and therapeutic implications.

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“…Although the cardiac phenotype was atypical for LMNA cardiomyopathy, the neuromuscular manifestations were similar to those commonly observed in patients with LMNA variants 11 …”

Section: Discussionsupporting

confidence: 57%

Section: Discussionsupporting

confidence: 55%

Genotype–phenotype correlation of LMNA variants involving the Arg541 residue: a case report with multimodality imaging and literature review

et al. 2020

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“…This association has not been reported in previous cohorts. Recent multicentric study reviewed the cardiac and neurologic involvement of laminopathies, concluding that most patients show neurologic symptoms by their fourth decade and develop cardiac involvement at the following decade (29). Our cohort is a bit in contrast to these data.…”

Section: Discussionmentioning

confidence: 76%

Cardiovascular Involvement in Pediatric Laminopathies. Report of Six Patients and Literature Revision

Baban¹,

Cicenia²,

Magliozzi

et al. 2020

Front. Pediatr.

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Lamin A/C (LMNA) encodes for two nuclear intermediate filament proteins. Mutations in LMNA cause a highly heterogeneous group of diseases predominantly leading to muscular or cardiac disease, lipodystrophy syndromes, peripheral neuropathy, and accelerated aging disorders. Cardiac involvement includes progressive arrhythmias (brady/tachyarrhythmias, sudden cardiac death). Furthermore, cardiomyocyte damage often progresses into dilated cardiomyopathy (DCM), rarely described in the pediatric age group. Neuromuscular manifestations are even rarer in children. We report on six pediatric patients with LMNA mutations: patient 1 was operated on for aortic coarctation, non-compact left ventricle, atrial fibrillation (AF) preceding the diagnosis of DCM; patient 2 was operated on for ventricular septal defect (VSD), developed after years malignant arrhythmias preceding the progression to DCM (left ventricular non-compaction with LV dysfunction); patient 3 had ectopic atrial tachycardia as first manifestation of a DCM; patients 4 and 5 had no major arrhythmic events but only dilated ascending aorta, mildly dilated LV with mild hypertrabeculation of the lateral wall and a normally functioning but dilated left ventricle, respectively; patient 6 showed aortic coarctation, supraventricular tachycardia. Paroxysmal AF occurred in patients 1, 2, and 3 (50% of cases). Our series highlight the coexistence of congenital heart defects (CHDs) and aortic involvement with laminopathies in four of our patients: consisting of aortic coarctation (two patients), aortic root dilatation (one patient), and VSD (one patient). Aortic changes in laminopathies have been reported only once in an adult patient. This is the first report in the pediatric setting, and no associations with CHD have been previously described.

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“…Patients who have both cardiac and neuromuscular manifestations more commonly experience bradyarrhythmias and atrial fibrillation compared to patients with solely cardiac phenotypes, despite having no differences in structural heart disease. In this group of patients cardiac abnormalities do not strictly correlate with the severity of the neuromuscular involvement, which may suggest distinct pathogenetic mechanisms (Benedetti et al, 2007;Hasselberg et al, 2018;Peretto et al, 2019). However, a recent study on a small cohort of patients showed that the neuromuscular presentation was associated with earlier cardiac involvement, characterized by a linear and progressive evolution from rhythm disorders to cardiomyopathy (Ditaranto et al, 2019).…”

Section: Clinical Presentationmentioning

confidence: 78%

The Broad Spectrum of LMNA Cardiac Diseases: From Molecular Mechanisms to Clinical Phenotype

Crasto

Pasquale

2020

Front. Physiol.

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Mutations of Lamin A/C gene (LMNA) cause laminopathies, a group of disorders associated with a wide spectrum of clinically distinct phenotypes, affecting different tissues and organs. Heart involvement is frequent and leads to cardiolaminopathy LMNA-dependent cardiomyopathy (LMNA-CMP), a form of dilated cardiomyopathy (DCM) typically associated with conduction disorders and arrhythmias, that can manifest either as an isolated event or as part of a multisystem phenotype. Despite the recent clinical and molecular developments in the field, there is still lack of knowledge linking specific LMNA gene mutations to the distinct clinical manifestations. Indeed, the severity and progression of the disease have marked interindividual variability, even amongst members of the same family. Studies conducted so far have described Lamin A/C proteins involved in diverse biological processes, that span from a structural role in the nucleus to the regulation of response to mechanical stress and gene expression, proposing various mechanistic hypotheses. However, none of those is per se able to fully justify functional and clinical phenotypes of LMNA-CMP; therefore, the role of Lamin A/C in cardiac pathophysiology still represents an open question. In this review we provide an update on the state-of-the-art studies on cardiolaminopathy, in the attempt to draw a line connecting molecular mechanisms to clinical manifestations. While investigators in this field still wonder about a clear genotype/phenotype correlation in LMNA-CMP, our intent here is to recapitulate common mechanistic hypotheses that link different mutations to similar clinical presentations.

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Cardiac and Neuromuscular Features of Patients WithLMNA-Related Cardiomyopathy

Cited by 36 publications

References 19 publications

Genotype–phenotype correlation of LMNA variants involving the Arg541 residue: a case report with multimodality imaging and literature review

Genotype–phenotype correlation of LMNA variants involving the Arg541 residue: a case report with multimodality imaging and literature review

Cardiovascular Involvement in Pediatric Laminopathies. Report of Six Patients and Literature Revision

The Broad Spectrum of LMNA Cardiac Diseases: From Molecular Mechanisms to Clinical Phenotype

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