Garmany Ramin, Neves Raquel, Ali Ahmed Fatima, Tester David J, Cannon Bryan C, Giudicessi John R, Ackerman Michael J
Mayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic Alix School of Medicine and the Mayo Clinic Medical Scientist Training Program, Rochester, MN 55905, USA.
Department of Molecular Pharmacology & Experimental Therapeutics, Windland Smith Rice Sudden Death Genomics Laboratory, Mayo Clinic, Rochester, MN 55905, USA.
Eur Heart J Case Rep. 2022 Mar 17;6(5):ytac115. doi: 10.1093/ehjcr/ytac115. eCollection 2022 May.
Pathogenic variants in the lamin A/C gene (LMNA) can lead to a wide range of phenotypes from dilated and arrhythmogenic cardiomyopathies and conduction abnormalities to partial lipodystrophies. This case highlights a coincidental pathogenic LMNA variant identified in a patient with sudden cardiac arrest (SCA). We demonstrate the need for careful interpretation of pathogenic variants identified in cardiomyopathy genes by highlighting a case in which a coincidental pathogenic LMNA variant was found in a patient with premature ventricular complex (PVC)-induced ventricular fibrillation (VF).
We present the case of a 16-year-old male with SCA secondary to VF. Genetic testing identified a maternally inherited pathogenic variant in LMNA annotated c.1961dup; p.T655Nfs*49. The patient received an implantable cardiac defibrillator and was discharged on nadolol. The patient's two brothers were also variant-positive. However, the patient and both brothers had normal chamber dimensions on echocardiogram and no late gadolinium enhancement on cardiac magnetic resonance imaging. The family members with the variant were recommended to have prophylactic implantable cardiac defibrillators and thus sought a second opinion. The patient received an appropriate shock and device interrogation identified PVCs. Electrophysiology study identified PVC-induced VF which was ablated with no recurrent ventricular arrhythmias/implantable cardioverter defibrillator therapies over 8 months of follow-up. Although the variant in LMNA could lead to cardiac arrest, the clinical phenotype was consistent with a non-genetic aetiology. The family members were told to have periodic cardiac evaluation.
This case demonstrates the identification of a coincidental pathogenic variant in a cardiomyopathy gene in a patient with cardiac arrest. Although this variant could lead to cardiomyopathy, it appears the cardiac arrest was not due to the pathogenic variant. This highlights the need to consider the clinical phenotype when interpreting genetic test results for cardiomyopathies even in the presence of a positive genetic test result.
核纤层蛋白A/C基因（LMNA）的致病变异可导致多种表型，从扩张型和致心律失常性心肌病、传导异常到部分脂肪营养不良。本病例突出了在一名心脏骤停（SCA）患者中偶然发现的致病性LMNA变异。我们通过一个病例强调了对心肌病基因中鉴定出的致病变异进行仔细解读的必要性，该病例中在一名室性早搏（PVC）诱发心室颤动（VF）的患者中发现了偶然的致病性LMNA变异。
我们报告了一名16岁男性因VF继发SCA的病例。基因检测发现LMNA基因存在一个母系遗传的致病变异，注释为c.1961dup；p.T655Nfs*49。患者接受了植入式心脏除颤器，并服用纳多洛尔出院。患者的两个兄弟也是变异阳性。然而，患者及其两个兄弟的超声心动图显示心腔大小正常，心脏磁共振成像未显示晚期钆增强。建议携带该变异的家庭成员植入预防性植入式心脏除颤器，因此他们寻求了第二种意见。患者接受了适当的电击，设备检查发现了PVC。电生理研究确定为PVC诱发的VF，并进行了消融，随访8个月无复发性室性心律失常/植入式心律转复除颤器治疗。尽管LMNA基因变异可能导致心脏骤停，但临床表型与非遗传病因一致。告知家庭成员定期进行心脏评估。
本病例显示在一名心脏骤停患者的心肌病基因中发现了偶然的致病变异。尽管该变异可能导致心肌病，但心脏骤停似乎并非由该致病变异引起。这突出了在解读心肌病基因检测结果时，即使基因检测结果为阳性，也需要考虑临床表型。
