P431 Steroid treatment may change natural history in congenital laminopathies

Mutations in LMNA gene lead to a broad spectrum of muscle disorders from congenital (L-CMD) to later onset muscular dystrophies (Emery Dreifuss type, EDMD). Patients with congenital laminopathies start before the age of 2 years and show a poor motor development or a rapidly progressive course after initial sitting or walking acquisition. A recognizable cervico-axial weakness (Dropped Head Syndrome, DHS) is observed, followed by constant loss of function of the extremities and respiratory muscles. Lordo-scoliosis and cardiac involvement (arrhythmias, heart failure) are later complications. Treatment with corticosteroids has been suggested as a potential therapy because of inflammatory changes observed on muscle biopsy. We describe the experience treating with corticosteroids children with L-CMD in three French Neuromuscular Paediatric Centers (FILNEMUS). A retrospective study was performed in all the children with genetically confirmed skeletal muscle laminopathies with onset at the paediatric age and treated by oral corticosteroids, at least during one year, in three paediatric neuromuscular centers. Collected data included molecular, clinical features and respiratory, motor, and heart functions, and ancillary tests (biopsy, muscle imaging, spinal X -rays, CK and Pro-BNP levels). Seven children (6 DHS, 1 EDMD), all carrying de novo LMNA mutations, were treated with prednisone (0.75 mg/Kg/day) at a mean age of 4 years (2-8) during an average of 3 years (1-7). Six of the patients were males. Inflammatory signs were observed in all, either on biopsy (2) or in the whole body muscle MRI pre-therapeutic examinations (5). Three boys younger than 2 years, who had never walked unsupported and were losing head, trunk and limb function, improved significantly after prednisone and were able to walk several weeks or months after treatment onset (2 weeks-1 year). A 4-year-old boy who lost walking, recovered this ability 2 years after starting prednisone. Both ambulant patients with DHS phenotype (a boy and a girl) remained ambulant (1-3 years). The girl showed a decrease of leg pain, significant decrease of CK levels and normalisation of Pro-BNP and Troponin blood results after treatment. Joint contractures were milder than expected in follow-up, except for the ankles. Spine did not show the typical stiffness but rather a hyperlordotic deformity, leading to an unexpected new phenotype. Corticosteroid treatment was discontinued in the only EDMD patient, a 12-year-old boy after 3 years of treatment, due to worsening of motor and cardiac status. Treatment with corticosteroids seems to stop progression of muscle weakness and contractures in congenital skeletal laminopathies when inflammation is present on muscle biopsy or imaging. Moreover, acquisition of new motor functions and striking improvement of axial and head support is observed in the weeks or months after onset of treatment. We observed only a clear beneficial effect in young children with de novo LMNA mutations treated before the age of 4 years. Muscle MRI may be useful to assess the presence of inflammation before treatment and as a potential biomarker during follow-up of the patients