Congenital Myasthenic Syndromes

260^th ENMC International Workshop:

Location: Hoofddorp, The Netherlands

Title:  Congenital Myasthenic Syndromes

Date: 11 -13 March 2022

Organisers:

Dr Pedro Rodriguez-Cruz (SEN)
Dr Lorenzo Maggi (IT)
Prof. Hanns Lochmüller (UK)
Prof. David Beeson (UK)

Translations of this report by:

Turkish: Dr Duygu Selcen
Italian: Dr Lorenzo Maggi
German: Dr Andreas Roos

Participants:

Dr Patricio Sepulveda (Australia), Mr. Roeland van Hauwaert (Belgium), Dr Sally Spendiff (Canada), Mrs. Marguerite Friconneau (France), Dr Andreas Roos (Germany), Prof. Hanns Lochmüller (Canada), Prof. Ulrike Schara (Germany), Dr Lorenzo Maggi (Italy), Dr Pedro Rodriguez-Cruz (Senegal), Dr Daniel Natera-de Benito (Spain), Mr Ignacio Escuder (Spain), Dr Andres Nascimento (Spain), Dr Duygu Selcen (USA), Dr Margherita Milone (USA), Prof. Steve Burden (USA), Dr Carsten Bönnemann (USA), Dr Yin Dong (UK), Prof. David Beeson (UK), Prof. Francesco Muntoni (UK), Dr Jackie Palace (UK), Dr Sithara Ramdas (UK)

The ENMC hosted a group of experts on Congenital Myasthenic Syndromes (CMS) from March 11-13, 2022 in Hoofddorp, The Netherlands. CMS are inherited disorders in which the safety margin of the neuromuscular transmission is compromised by one or more specific mechanisms. CMS are caused by various genetic defects of neuromuscular junction proteins and in some instances more widely expressed glycosylation genes. Since the last ENMC workshop on CMS in 2011 (186th workshop), additional CMS genes have been identified through next-generation sequencing. Better understanding of the molecular mechanisms and progress in biotechnology has led to the development of new therapeutic approaches such as AAV gene therapy and MuSK agonist antibody therapy showing promising results in animal models. However, the scarcity and diversity of this rare condition poses challenges for clinical trial design, planning and recruitment, as a more detailed understanding of progression, measurement of outcomes, sharing of clinical data and samples and development of biomarkers is required. The workshop discussed the underlying pathophysiology, animal models, current and future approaches to diagnosis and therapies of CMS. Furthermore, the group identified gaps in current knowledge and made plans for future collaborative efforts such as comparison of laboratory and clinical protocols, sharing of preclinical and clinical data, utilization of European data infrastructures such as the EURO-NMD registry and joined efforts towards clinical trial readiness. The workshop was attended by 21 participants from 10 countries (Australia, Belgium, Canada, France, Germany, Italy, Senegal, Spain, United Kingdom, U.S.A.), 6 of them remotely due to pandemic travel restrictions. Participants included scientists, clinicians, industry and two patient representatives. CMS patients are often responsive to treatment with different, already available medications, but early and correct diagnosis remains challenging. The awareness and understanding for CMS among health care professionals and the lay public requires further attention.

A full report will be published in Neuromuscular Disorders (full report 260)