A Natural History Study of Congenital Myasthenic Syndromes (CMS)
Research type
Research Study
Full title
A Natural History Study of Congenital Myasthenic Syndromes, to establish reliable outcome measures suitable for clinical and research assessment
IRAS ID
289835
Contact name
Hayley Ramjattan
Contact email
Sponsor organisation
Oxford University Hospitals
Duration of Study in the UK
2 years, 0 months, 0 days
Research summary
Congenital Myasthenic Syndromes (CMS) are a group of rare genetic disorders affecting the neuromuscular junction structure and function (Finlayson, et al. 2013). They are characterised by the presence of fatigable muscle weakness, but age at onset, presenting symptoms, distribution of weakness, and response to treatment differ depending on the molecular mechanism that results from the genetic defect (Rodriguez Cruz et al. 2014). The severity of CMS is highly variable amongst individuals and can fluctuate and worsen with physical effort, which makes assessing this population a challenge. (Angelini. 2014).
The main types of CMS include DOK7 CMS, epsilon (ε) sub-unit of the acetylcholine receptor (AChR) mutations causing AChR deficiency, Rapsyn CMS, slow channel CMS, fast channel CMS, COLQ CMS and glycosylation mutation CMS. The first three make up approximately 60% of the total in the UK.
There are currently no validated outcome measures for use in CMS and the heterogeneity of these syndromes causing different distributions of weakness means a generic outcome could be less sensitive than a more focused genetic sub type approach. Additionally, many patients present in childhood where the age of the patient will affect the outcome measures used. Currently the HSS Oxford CMS Service, utilise outcome measures validated in Myasthenia Gravis and other neuromuscular conditions, to assess and monitor this patient cohort. This study looks to analyse this clinical data and compare it to other suitable outcome measures to identify which assessments are most suitable and sensitive to change in the CMS cohort.
Summary of results
Congenital Myasthenic Syndromes (CMS) are a group of rare genetic disorders affecting the neuromuscular junction function. They are characterised by fatigable muscle weakness with onset in most cases in infancy or early childhood. The severity of CMS is variable amongst individuals, fluctuating with physical effort, which can make objective assessments challenging. Currently, there are no validated outcome measures for use in CMS, and most clinicians use outcome measures validated in Myasthenia Gravis and other neuromuscular disorders. There is a need to establish validated outcome measures in CMS with the emerging novel treatments in the pipeline.
Forty patients with a range of genetically confirmed CMS subtypes were assessed for community physical activity analysis, with 37 conducting a corresponding clinic-based six-minute walking test.
This first-of-a-kind study highlights the variability in activity levels across the different CMS subtypes, describing the relationship between community physical activity and a standardised walking measurement in this CMS population. There was negligible correlation between distance walked in a six-minute walking test and community physical activity levels, with physical activity levels reflective of lifestyle choices. In addition, we have described the features of walking fatigue in this population in greater detail. Both may have implications in future CMS research and clinical management. Further analysis is planned.REC name
London - Bromley Research Ethics Committee
REC reference
21/LO/0480
Date of REC Opinion
4 Aug 2021
REC opinion
Further Information Favourable Opinion