G.P.145

Muscular dystrophy related to lamin A/C gene (LMNA/C) mutations is characterized by muscle weakness, joint contractures, dilated cardiomyopathy, and arrhythmias. It includes autosomal dominant and rare recessive forms of Emery-Dreifuss (EDMD) as well as limb-girdle muscular dystrophy (LGMD1B), dilated cardiomyopathy with conduction system disease and congenital muscular dystrophy (CMD). We describe the clinical and pathological spectrum of 13 patients with an LMNA/C gene mutation. Results: 13 patients (6 females/7 males) were studied. Eight patients with EDMD had progressive weakness with proximal hypotrophy in the upper limbs and distal hypotrophy of the lower limbs with neck, elbow, and Achilles heel contractures, and conduction-system cardiac involvement. Three patients with a CMD form, presented dropped-head syndrome with clinical onset in the first years of life. They had weakness and proximal hypotrophy of the upper limbs and distal hypotrophy of the lower limbs. One patient never walked and another lost ambulation afterwards. None of our patients showed cardiac involvement or elbow contractures. Two of our patients assumed as LGMD1B had proximal weakness without contractures. In one of them, the first sign was a dilated cardiomypathy that required transplantation. Four patients had a family history of heart disease or weakness. Muscle biopsy showed a variable degree of inflammatory and/or dystrophic changes, with lobulated fibers or type 1 atrophy and variable oxidative defects or increase in central oxidative activity. Ultrastructural study showed nuclear changes and focal sarcomeric disorganization. All patients had mutations of the LMNA/C gene. Conclusion: There is a broad clinical spectrum of laminopathies, including a congenital form. Even when muscle biopsy shows inflammation or features suggestive of congenital myopathy, the clinical phenotype should prompt molecular testing for lamin A/C mutations to prevent cardiac complications.