P.256Steroid treatment may change natural history in young children with LMNA mutations and dropped head syndrome

Abstract

LMNA congenital muscular dystrophy (L-CMD) is a rare devastating disease with severe and progressive course during childhood. Most patients achieve walking but they rapidly lose head and trunk support and are mechanically ventilated in the first decade of life. Inflammatory changes in the muscle biopsy may be observed and response to steroids has been reported occasionally. Describe the experience of treatment by corticosteroids in children with L-CMD followed in four Neuromuscular Pediatric Centers from different countries. A retrospective study was performed in 11 children (7 males) with genetically confirmed L-CMD treated by oral corticosteroids for more than one year. Data collection was reviewed including, steroid dose, histological findings, motor and respiratory function and cardiac tests at the time of treatment and during follow-up. All patients had a de novo mutation in LMNA gene and started with symptoms before 2 years of age. 72% acquired walking before treatment and most presented with dropped head phenotype (8 vs 3 Emery-Dreifuss). Mean age at treatment was 4 years (range 2-8). Dose range was 0.75-1 mg/Kg/day. Children were treated between 1 and 7 years. Steroids were stopped in two teenagers with EDMD owing to metabolic syndrome and cardiac worsening after 1 and 4 years respectively. Three children with dropped head syndrome treated before 3 years of age walked independently and developed a particular phenotype not observed in untreated children, with marked dorsal hyperlordosis but no major joint contractures. To date, 8 patients are still on treatment with maintained motor function and no major respiratory insufficiency. Treatment with oral steroids should be used with caution but might be beneficial in young LMNA mutated children presenting with a dropped head syndrome, in particular those treated before three years of age. Further studies with larger number of patients are required to confirm our results.