A multicenter cross-sectional and longitudinal study of the Swiss cohort of Merosin-negative congenital muscular dystrophy

Dr. Andrea Klein, UKBB Basel

Abstract

 

Congenital muscular dystrophy (CMD) with merosin deficiency (MDC1A) is an autosomal recessive disorder due to mutations in the laminin alpha-2 gene (LAMA2). Recently published data from a UK cohort showed, that MDC1A is the most common CMD. (1) Affected children present soon after birth with hypotonia and severe muscle weakness. Most of the children do not achieve independent ambulation. Characteristic symptoms of MDC1A are contractures, often quite severe, respiratory insufficiency with need of ventilation, external ophthalmoplegia and feeding difficulties with failure to thrive. Some patients however show a milder and more variable course of the disease with later onset, which often correlates with partial Merosin-deficiency in muscle biopsy immunohistochemistry staining. No clear genotype-phenotype-correlation has been reported as yet. 

To date treatment consists in a multidisciplinary care according to international standards. Currently there is no pharmacological treatment available, but promising therapeutic interventions are studied in animal models and recently a first therapeutic trial in this disease group, a phase-I-trial with an anti-apoptotic medication was conducted (CALLISTO by Santhera). 

Little data exists about the phenotypic spectrum and natural history of MDC1A and data on prevalence differ. (2,3) In this project, we want to conduct a cross-sectional study of the Swiss patients with MDC1A, determine prevalence in Switzerland, describe this cohort with descriptive statistics and compare with previously published cohorts. With possible therapeutic trials on the horizon detailed knowledge about the natural history is very important. Therefore we aim to assess the disease progression with a dataset on respiratory function, nutrition, contractures and complications and evaluate motor function on the basis of yearly physiotherapeutic assessments over 3 years. The data will be collected prospectively within the existing Swiss NMD registry for which an ethics application has already been approved for to get a better understanding of the disease progression in this disease.