Familial cardiolaminopathy due to a previously undescribed LMNA gene mutation

Abstract

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Cardiolaminopathies are rare genetic alterations, which present diverse mechanical and electrical alterations. OBJECTIVE To present a family carrying an LMNA gene mutation that although not described manifest clinical and electrocardiographic characteristics of the disease. Methods We present the case of two sisters and one brother, aged 65, 57 and 51 years, respectively. At the beginning of their fourth decade, all of them debuted with atrial flutter associated with second and third degree atrioventricular block. Two of them (one or the sisters and the brother) underwent ablation of isthmus-dependent atrial flutter. However, in both, the flutter recurred and no new interventional treatment was further offered. The male subject received a pacemaker implant for treatment of AV block; some years later, he presented a cerebrovascular event and subsequently a recurrence, both while in oral anticoagulation and, actually remains with moderate motor deficit and dysarthria. The youngest woman suffered an embolic cerebrovascular event when she was 50 y/o; she remained asymptomatic in relation to the rhythm disorder and refused a pacemaker. The oldest sister who is asymptomatic, received a pacemaker when she was 45 y/o and now is anticoagulated. By echocardiography, all siblings presented left ejection fraction in between 40 and 50% with decreased strain values and normal left ventricular geometry. Results Recently in our country it is possible to carry out a genetic test, for which the three were subjected to it. In this family, the genetic testing was done using a comercial kit for 172 genes. The result was a Frameshift Indels (non misense) mutation NM_170707.3 c.1526del p.(Pro509LeufsTer39) Exon:9/12, in all three. The caveat is that this LMNA gene mutation has not been previously described. In light of these results, the youngest woman with total AV block and sequelae of cerebrovascular disease and mild left ventricular dysfunction, received an implantable cardiac defibrillator (ICD) implant for primary prevention of sudden death and her siblings are undergoing an upgrade to ICD. Conclusion The mutation found in this family is unique and for the first time reported in the LMNA gene in the world. Genetic diagnosis is limited in our country, which makes it difficult to determine this type of pathology. However, given the clinical presentation of an electrical disorder in all the siblings of a family, in this particular case, it was mandatory to perform this test. These results allow us to better understand the prognosis and intervene appropriately to prevent sudden death, even though there is no treatment to avoid the progression of the disease.