The Myotubular and Centronuclear Myopathy (MTM and CNM) Patient Registry is an international, patient-reported database created to capture clinical and genetic data from patients who have been diagnosed with these ultra-rare genetic conditions and on female carriers of x-linked myotubular myopathy. The registry was established in March 2013 by the Myotubular Trust in collaboration with TREAT-NMD (an international neuromuscular network of clinicians and specialist centres) and other key opinion leaders, and was transferred to the John Walton Muscular Dystrophy Research Centre at Newcastle University in 2015. Below Lindsay Murphy provides a Patient Registry update.
Information in the registry is collected through a secure online portal, directly from the participants (or from a parent or guardian if the patient is under 18). We also welcome registration of deceased patients, if their family wishes to contribute their data. Online registration is available to all of these groups and can be done in English, German, Spanish, Polish, Italian or French. The main purpose of the registry is to aid the rapid identification of eligible patients for clinical studies when approached by researchers and pharmaceutical companies. The registry also disseminates disease-relevant information to participants; provides a source of information to academics, industry and healthcare professionals to support research and the development of standards of care; and seeks to provide support to the MTM and CNM community. To give a snapshot of some of the information held within the registry, a few current data items are presented below.
To date, a total of 249 participants are registered with the MTM and CNM Patient Registry. Participants have registered from across Africa, Europe, Asia, the Americas and Oceania, reflecting the registry’s truly global nature (see Figure 1).
Figure 1: Number of consented registrations by country
The age range of registry participants is from 0 to 74 years, and of those registered, 71.1% are patients, 11.9% are deceased patients and 10.9% are female carriers of the XLMTM gene.
The registry captures both the patient-reported medical diagnosis and the genetic diagnosis. A doctor will review a patient’s symptoms and perform tests to reach a medical diagnosis. Among the muscular dystrophies, symptoms may be very similar, therefore, to be certain of the cause of illness, it is important to have a genetic test. This will identify if a change or mutation in a specific gene is present and will provide a genetic diagnosis of a patient’s condition. If a patient wishes to participate in clinical trials it is of great importance to obtain a genetic diagnosis as this if often a specific requirement of trial coordinators.
Information captured by the registry on medical diagnosis illustrates that most living registry participants have MTM (65.3%), with the remaining participants having CNM (28.6%) or either an unconfirmed or ‘other’ diagnosis (6.2%, see Figure 2).
Figure 2: Medical diagnoses of living registry patients
The genes associated with the conditions MTM and CNM in living patients are presented in Figure 3. Mutations within the X-linked MTM gene are most commonly associated with a medical diagnosis of MTM. In comparison, the genetic causes of CNM are attributed to a wider number of genes, most notably dynamin 2 (DNM2) and skeletal muscular ryanodine receptor (RYR1).
Figure 3: Living registry patients by gene mutation, stratified by diagnosis
Recruitment to clinical trials and research studies is one of the main purposes of the registry, and has proven to be highly successful. Participants have been informed of, and recruited to, a number of such studies, including:
- Natural History Study of MTM patients at the Institute of Myology
- ‘INCEPTUS: A Clinical Assessment Study in X-Linked Myotubular Myopathy’, carried out by Audentes Therapeutics
- Genetic Alliance Survey about preimplantation genetic diagnosis for CNM patients with a variant in the DNM2 gene
- ‘Journeying: a research project exploring the experiences of power wheelchair users in the built environment and on public transport’.
The registry has also helped support the promotion of surveys and studies, including a long-term ventilation survey for patients and their carers and an academic research study investigating physical activity in patients with various neuromuscular conditions.
The MTM and CNM Patient Registry is a highly successful venture for participants, clinicians and academics alike, however, there is always room for improvement. With that in mind, we are hoping to add the ability for doctors to contribute clinical data from their consenting patients, which may help to address the patient language barrier and issues related to internet access. Also, clinician verification of patient-entered data will help to assure data quality.
For further information about the MTM and CNM Patient Registry, please visit the registry website.