International Journal of Cardiology 181 (2015) 48–49

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Letter to the Editor

Lamin A/C mutation: An easily missed opportunity Susie Parnham a,b,⁎, Joseph B. Selvanayagam a,b, Eric Haan c,d, William Heddle a,b, Carmine G. De Pasquale a,b a

Department of Cardiovascular Medicine, Flinders Medical Centre, Australia School of Medicine, Flinders University, Australia South Australian Clinical Genetics Service, SA Pathology (at Women's and Children's Hospital), North Adelaide, Australia d School of Paediatrics and Reproductive Health, The University of Adelaide, Adelaide, Australia b c

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Article history: Received 27 November 2014 Accepted 1 December 2014 Available online 3 December 2014 Keywords: A/C lamin mutation LMNA Laminopathy Cardiomyopathy

To the Editor: Conduction disorders in the setting of cardiomyopathy impose significant management challenges. We present a case of incidental early dilated cardiomyopathy (DCM) with significant first degree heart block due to lamin A/C (LMNA) gene mutation, a diagnosis not to be missed given the severity of the disease and the possibility of early interventions to prevent progression to overt heart failure and premature sudden cardiac death. A 50-year-old man presented with atypical chest discomfort. Cardiac risk factors were hypertension, diabetes mellitus type 2, and hypercholesterolemia; his brother had sudden cardiac death at 51. His medications were amlodipine 5 mg, atorvastatin 40 mg, candesartan 16 mg, hydrochlorothiazide 12.5 mg, and aspirin 100 mg daily. The electrocardiograph showed significant first degree heart block with PR interval 400 ms (Fig. 1A). Holter monitor showed chronotropic abnormalities (minimum rate 30 bpm, maximum 115 bpm), a longest pause of 2.4 s and ventricular complexes, including triplets (Fig. 1B). Transthoracic echocardiography showed a dilated left ventricle with an ejection fraction of 55% and a dilated left atrium. Exercise stress test showed frequent ventricular complexes with triplets and bigeminy. Peak heart rate after 13 min of exercise (Bruce protocol) was 83% maximum predicted. Cardiac magnetic resonance imaging showed increased ⁎ Corresponding author at: School of Medicine, Flinders University, Australia. E-mail address: [email protected] (S. Parnham). 0167-5273/© 2014 Elsevier Ireland Ltd. All rights reserved.

biventricular volumes with late gadolinium hyperenhancement in mid wall septal region (Fig. 1C). Full blood count, thyroid function, electrolytes, renal function, C-reactive protein, iron studies, and NT-pro brain natriuretic peptide were normal, however creatine kinase (CK) was elevated at 585 units/L (normal: 20–180 units/L). DCM with associated conduction abnormalities, family history of sudden cardiac death, and elevated CK are suggestive of laminopathy. Genetic testing identified the LMNA mutation c.80C N G (p.Thr27Ser). This mutation has not previously been described in mutation databases, however is likely pathogenic given that another amino acid substitution at the same position (p.Thr27lle) and amino acid substitutions at surrounding amino acids are known to cause laminopathies associated with DCM ( This case illustrates how a thorough clinical history, examination and investigations have led to a diagnosis of laminopathy with potential major implications for the patient and family. In LMNA mutation carriers, arrhythmia was reported in 92% after age 30, heart failure in 64% after age 50, with frequent sudden cardiac death (46%) [1]. LMNA mutation was detected in 8% of families with DCM [2], and carriers have poor eventfree survival of only 31% versus 75% in non-carrier DCM patients [3]. Implantable cardioverter-defibrillator (ICD) has been shown to be effective in primary prevention of sudden cardiac death in patients with LMNA mutation [4]. This patient was referred for implantable cardioverter defibrillator with pacing capability (CRT-D), due to the pacing indication in the setting DCM and the need for primary prevention ICD. Conflict of interest The authors report no relationships that could be construed as a conflict of interest. References [1] J.H. van Berlo, W.G. de Voogt, A.J. van der Kooi, et al., Meta-analysis of clinical characteristics of 299 carriers of LMNA gene mutations: do lamin A/C mutations portend a high risk of sudden death? J. Mol. Med. (Berl.) 83 (1) (2005) 79–83. [2] M. Pasotti, C. Klersy, A. Pilotto, et al., Long-term outcome and risk stratification in dilated cardiolaminopathies, J. Am. Coll. Cardiol. 52 (15) (2008) 1250–1260. [3] M.R. Taylor, P.R. Fain, G. Sinagra, et al., Natural history of dilated cardiomyopathy due to lamin A/C gene mutations, J. Am. Coll. Cardiol. 41 (5) (2003) 771–780. [4] C. Meune, J.H. Van Berlo, F. Anselme, et al., Primary prevention of sudden death in patients with lamin A/C gene mutations, N. Engl. J. Med. 354 (2) (2006) 209–210.

S. Parnham et al. / International Journal of Cardiology 181 (2015) 48–49


Fig. 1. Cardiomyopathy due to LMNA mutation. Panel A shows a markedly prolonged PR interval on ECG. Panel B showed pauses and ventricular triplet. Panel C showed dilated cardiomyopathy with subtle mid septal wall fibrosis (arrow).

C mutation: An easily missed opportunity.

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