954 DILATED CARDIOMYOPATHY AND ATRIOVENTRICULAR BLOCK RELATED TO THE MUTATION IN THE LMNE GENE: DESCRIPTION OF A FAMILY

Abstract The proband was patient A2, suffering by severe left ventricular dysfunction (EF 20%) and II degree Mobitz type 1 atrioventricular block, requiring dual chamber ICD implantation, retinitis pigmentosa. He had three brothers A1, A4, A5 also dilated cardiomyopathy ICD/CRTD recipients. His sister A3, his daughter B1 the firstborn brother A1 were affected Genetic analysis performed in A2 NGS of a panel genes related to heart disease It documented presence missense pathogenetic variant (class 4) LMNA gene heterozygosis (c.949G>A). This has been described several scientific papers as associated with cardiac impairment patients from block cardiomyopathy. Laminin A/C is fundamental protein nuclear envelope cell. Germline mutations gene, present on chromosome 22 (1q22), encoding lamina, have causally linked four different diseases 42 reported mutations: Dilated (DCM) conduction system; Limb girdle muscular dystrophy (LGMD); Autosomal dominant Emery-Dreifuss (EDMD); partial lipodystrophy. LMNA-related characterized enlargement and/or reduced systolic function frequently preceded or accompanied significant system disease. Family studies suggest that commonly precedes development DCM few years decade more. Conduction involvement usually starts sinus node can manifest bradycardia, arrest junctional rhythms, (commonly first-degree progresses second- third-degree block). following are common: symptomatic bradyarrhythmias pacemakers, supraventricular arrhythmias including atrial flutter, fibrillation, tachycardia, sick syndrome (i.e., tachycardia-bradycardia syndrome), frequent premature contractions tachycardia Sudden death may occur progressive Although more malignant, life-threatening longstanding previously DCM, sudden be presenting manifestation minimal no dysfunction. In cardiological setting, AVB reliable marker for molecular screening. Regarding pigmentosa, c538C>G found RHO proband, classifiable pathogenetic. encodes necessary retinal photoreceptors pathogenic 30-40% hereditary forms conclusion, we believe tests carried out confirmed hypothesis form which seem segregate independently family. Both transmitted 50% cases, regardless sex. For this reason recommended extend genetic all relatives (siblings children).