Skeletal muscle channelopathies: severe infantile phenotypes and sudden infant death syndrome (360G-Wellcome-209583_Z_17_Z)

Skeletal muscle channelopathies are mainly autosomal dominant disorders that typically cause muscle symptoms of myotonia, periodic paralysis or progressive myopathy. Until now the muscle channelopathy phenotypes described are disabling but not fatal. Pilot data implicates ion channel dysfunction in severe infantile phenotypes with respiratory compromise and some cases of sudden infant death syndrome (SIDS). Aims: Investigate ion channel genetic architecture in new cohorts of infants with life-threatening apnoeas and 300 SIDS cases. Determine if age related differences in ion channel expression and muscle fibre type contribute to disease severity. Build a national SIDS registry with experts and charities to enhance clinical correlation and interpretation of genetic/ in vitro findings. Methods: Whole exome, NGS sequencing and MLPA. Immunohistochemistry, western blotting and RNA analysis of control respiratory, skeletal and cardiac muscle at 0 to 24 months. Questionnaire covering pregnancy and post-natal period for affected patients. Web-based database collecting detailed clinical and genetic data of SIDS, tissue samples collected in biobank. Opportunities: proposes a totally novel mechanism of pathogenesis in SIDS. Inform understanding of normal developmental changes of skeletal and cardiac muscles. A national SIDS registry and biobank will be an invaluable research resource. Key words: ion channelopathies, respiratory, sudden infant death