Trial Readiness and Endpoint Assessment in Congenital and Childhood Myotonic Dystrophy

Children with congenital myotonic dystrophy (CDM) present at birth with respiratory insufficiency, talipes equinovarus, feeding difficulties and hypotonia. There is a 30% mortality rate in the first year of life. Children with childhood onset myotonic dystrophy present with symptoms later on but soon develop behavioural difficulties and learning difficulties and are at risk for autistic features and gastrointestinal symptoms. The ability to conduct a therapeutic trial in children with CDM or ChDM is directly limited by the lack of available data regarding appropriate clinical endpoints and biomarkers. Whereas there is an active Italian collaboration recruiting adults with DM1 to study muscle and multisystem aspects in this population, there is no active network in Italy involved in the pediatric population with DM1. Though the underlying mechanism is the same in adult DM1, in CDM and ChDM there are specific challenges to the pediatric population. The aim of this project is to coordinate the Italian Child Neurologist actively involved with CDM and ChDM in a common effort of standardizing protocols and procedures to be applied in the care of these patients. Specific aims are to collect functional measures and clinical information over time to define clinically meaningful endpoints and outcome measures in preparation for international therapeutic clinical trials. This project will contribute to the ongoing international study in CDM by recruiting additional patients from all over Italy and will extend the investigations to the childhood onset forms as an additional add-on pilot study in view of potential treatment options. The investigators expect that the Italian network, with Telethon support, will provide the necessary backbone for trial readiness in the pediatric population both at the national and international levels.