Brain Involvement in Dystrophinopathies Part 1

NHS Foundation Trust

Status: Completed

Conditions: Becker Muscular Dystrophy; Duchenne Muscular Dystrophy

Study type: Observational

Funder types: Other

Identifiers

NCT04583917

20NM34

Details and patient eligibility

About

The objective of this study is to collect data from a large cohort of individuals with DMD and BMD focusing on the neurobehavioural aspects of these conditions and their correlation to the location of the DMD gene mutation.

Full description

Intellectual disability and neurobehavioural comorbidities affect at least 50% of the individuals with Duchenne muscular dystrophy (DMD), which, although a rare genetic disease, is the most common form of muscular dystrophy in childhood. Several studies have documented that 25% of the DMD population has intellectual disability with recent studies suggesting that autism and clinically relevant hyperactivity affects 20% and 25% of DMD boys respectively. A milder allelic variant, named Becker muscular dystrophy (BMD), has similar prevalence in the population and is also associated with variable degrees of central nervous system (CNS) comorbidities, which however have been less well defined.

The investigators will address these deficiencies in a large multicentre study funded by the European Commission (EU H2020) involving 6 countries (Denmark; The Netherlands; France; Spain; Italy and UK) with the largest European neuromuscular centres and advocacy groups. The aim will be to study the neurobehavioural aspects of DMD and BMD as well as their correlation to the genotype. This study will involve male participants with DMD aged 5-17 years and with BMD aged 5-50 years. It will comprise of online questionnaires that will be completed either by a parent of a participant <17 years or an adult participant. The questionnaires take approximately 70 minutes to complete, however this can be done in multiple sittings. Currently there is a lack of information to assist the prognosis of CNS comorbidities, as existing databases and registries typically focus on the motor milestones and physical disability of these patients. There is therefore, an urgent need to present the course and outcomes in DMD and BMD patients with a wide range of DMD mutations, to provide information at the point of diagnosis and onwards for families, clinicians and service providers. It will also assist in paving the way to greater biological understanding and personalization of interventions.

Enrollment: 377 patients

Sex: Male

Ages: 5 to 50 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

For DMD patients:

• Male
• age 5-17 years
• genetically-proven diagnosis of DMD
• genetic mutation that abrogates expression of Dp427 alone (assigned in DMD Group 1: Dp427-/Dp140+) or both Dp427 and Dp140 (assigned to DMD Group 2: Dp427-/Dp140-); or all isoforms (assigned to DMD group 3)

For BMD patients:

• age 5-50 years
• genetically-proven diagnosis of BMD
• genetic mutation that decreases expression of Dp427 alone (assigned to BMD Group 1), of both Dp427 and Dp140 (assigned to BMD Group 2), or of all the isoforms (assigned to BMD group 3).

Exclusion criteria

• Lack of a molecular diagnosis of DMD or BMD
• Mutation falls outside the regions of interest
• A severe co-morbidity or planned surgical intervention within 6 months from the study which could interfere with the well-being of the participant