VP.70 OPALE: a patient registry for laminopathies and emerinopathies in France

Abstract

Laminopathies and emerinopathies are rare disorders due to mutations in A-type lamins (<i>LMNA</i>) and emerin (<i>EMD</i>) genes. Among them, disorders affecting striated muscle and fat tissues are the most frequent, with cardiac disease being a major cause of death. Clinico-genetic spectrum of these diseases have been extensively described since the 1990's. Precise phenotype/genotype relations remain elusive but several clues have been identified. Apart from symptomatic treatments, first specific treatments to prevent or slow down disease progression are undergoing therapeutic trials. Since 2013, we developed opale, an approved multicenter web-based registry dedicated to laminopathies and emerinopathies French patients. The main inclusion criterion is the presence of a proven pathogenic (or likely pathogenic=ACMG class 4) <i>LMNA</i> or <i>EMD</i> gene mutation. OPALE's objectives are to provide detailed capture of patient genetic data, neuro-cardio-endocrinological and respiratory assessments, in order to allow <i>i)</i> precise characterization of disease natural history, <i>ii)</i> estimation of the prevalence of various complications and <i>iii)</i> identification of prognostic factors. Currently, opale gathers 28 centers including neurological and/or cardiological and/or endocrinological departments. A total of 766 patients (749 <i>LMNA</i> and 17 <i>EMD</i> mutated) have been already included and 230 additional patients (141 <i>LMNA</i>, 89 <i>EMD</i>) are currently screened for a future inclusion. The clinical spectrum of the included patients comprises 108 asymptomatic mutation carriers (102 <i>LMNA</i>, 6 <i>EMD</i> mutated), 232 with isolated cardiac disease (228 <i>LMNA</i>, 4 <i>EMD</i> mutated), 267 with myopathy with or without cardiac disease (260 <i>LMNA</i>, 7 <i>EMD</i> mutated), 88 <i>LMNA</i> mutated with lipodystrophy, 7 <i>LMNA</i> mutated with peripheral nerve disease, 16 <i>LMNA</i> mutated with progeria or progeroid phenotypes and 42 <i>LMNA</i> mutated with diverse muscle-heart-fat-nerve-progeroid overlapping features. The remaining patients are undergoing clinical characterization. We also set up a prospective quantitative muscle evaluation study to follow muscle involvement natural history and a serum biobanking to explore blood biomarkers. OPALE registry is currently the largest registry dedicated to laminopathies and emerinopathies. It allows a better understanding of the clinico-genetic spectrum.