P.1.15 Clinical heterogeneity of myopathy related to partial merosin deficiency

Mutations in the LAMA2 gene underlie a severe congenital type of muscular dystrophy (MDC1A). We report the clinical, histological and genotypic features of 2 patients aged respectively 35 and 31 years-old, presenting unusual phenotypes. The first patient, aged 36, exhibit a late-onset muscle weakness predominantly in the limb girdle. Contractures of the elbow, wriest, fingers and Achilles tendons were the first symptoms with an onset at 15 years of age. Pelvic muscle weakness was observed at 25 years of age. The CK was elevated (2000 UI/L). In addition, he presented at age 30 a dilated cardiomyopathy with ventricular arrhythmias, requiring the implantation of a cardioverter-defibrillator. The second patient, aged 31 years, presented axial weakness at age 1, followed by the occurrence of rigid spine around 10 years of age associated to contractures at elbow, fingers, hips and Achilles tendons. At age 30, he had predominantly axial and limb girdle muscle weakness associated with upward gaze deficit. He has also generalized and partial complex seizures, beginning at age 6. The brain MRI disclosed bilateral occipital polymicrogyria and lissencephaly. Muscle histology showed dystrophic features, rimmed vacuoles, and partial loss of laminin a immunoreactivity. Nerve conduction study was normal in both patients. High-throughput analyses using “NMD-Chips” DNA capture and next generation sequencing identified novel nonsense mutations of LAMA2 gene at homozygous stage in the two patients. Previous sequencing of LMNA, EMD, DES, FHL1, MYH7, FKRP, FKTN, COL6A1,2,3, SEPN1 genes disclosed no mutation. In summary, these 2 patients disclosed a mild limb-girdle-type pattern of weakness and contractures associated respectively in each patient with dilated cardiomyopathy and cortical dysplasia. Work partly supported by the NMD-CHIP Consortium, an European Commission FP7 HEALTH project (HEALTH-F5-2008-223026).