This lay summary has been extracted from the peer reviewed publication, “229th ENMC international workshop: Limb girdle muscular dystrophies – Nomenclature and reformed classification Naarden, the Netherlands, 17–19 March 2017”
Historically, the nomenclature, or system of naming of diseases has not been consistent. Some diseases have been named by cause or presenting symptoms, some have been named by pathological features and organs involved, and still others were named after the experts that first described them (for example, Ullrich CMD). Yet as science improves and we learn more about a condition, we often need to revisit and update nomenclature in order to maintain accuracy and appropriately categorize conditions for the benefit of all.
The limb girdle muscular dystrophies (LGMD) form a group of diseases for which the current classification systems have reached their usefulness. At the 229th ENMC workshop in March 2017, many of the world’s top experts — including many familiar to the CMD community, including Dr. Carsten Bönnemann, Dr. Anna Sarkozy, Dr. Volker Straub, and Dr. Bjarne Udd — met to address this dilemma and identify an improved classification system for this heterogeneous group of conditions.
How Was LGMD Originally Named?
The term “limb girdle muscular dystrophy” was first introduced in 1954 in a paper by Walton and Natrass, clinically separating these conditions from other forms of muscular dystrophy such as Duchenne. In 1995, researchers developed the first LGMD classification nomenclature — an alphanumeric system that avoided imprecise and often lengthy condition names. In the original system, the number “one” or “two” was assigned depending on the mode of inheritance: dominant or recessive, and a letter was assigned based on the order of discovery. Today, more than 30 types of LGMD have been characterized using this system.
Why Must the Name be Updated?
As with many conditions that have a wide spectrum of symptoms, the existing system has become a significant problem as improvements in science and technology have led to more frequent and speedier discoveries. With exome and genome sequencing, it is likely that numerous new types of LGMD will be identified in the coming years. Yet once classifications exceed LGMD 2Z, no agreed-upon LGMD names will remain. Additionally, with the exception of autosomal inheritance, the 30+ LGMD subtypes that exist have very little in common with one another. Thus, new nomenclature is necessary.
A condition’s name is vital to its classification and the community’s overall understanding of it. From the research publication: “Because [the pharmaceutical] industry is starting to show increased interest in LGMD, it will be important to have clarity about the classification of diseases caused by mutations in the same gene, as this will affect feasibility studies, inclusion criteria for clinical trials and recruitment strategies.”
The 229th ENMC Meeting: March 2017
Aims of the second ENMC meeting to discuss LGMD nomenclature included:
Reach consensus on an updated definition of LGMD and to evaluate current subtypes of LGMD by application of the updated definition.
Review and evaluate suggestions of potential new classifications of LGMD subtypes.
Reach consensus on the most useful nomenclature and classification of LGMD subtypes that is accurate, scientific and with capacity to accommodate further discoveries of LGMDs.
Evaluate and discuss potential implications of a new definition or classification of LGMD for patients.
Over three days, the committee discussed common terms among genetic resources and rare disease organizations, common clinical denominators of pediatric and adult onset LGMDs, common denominators defined by investigations, and results from large-scale sequencing projects. Patient input was included in the discussion via patient advocacy organization representatives and social media. Some patients felt that changing the name or classification system could lead to confusion and fragmentation of their existing communities; others wanted the condition names to include as much detail as possible to allow for broad explanation.
And the Nomenclature Is…
After much discussion, the ENMC meeting attendees concluded that with the new nomenclature, some conditions formerly known as LGMDs no longer fit the definition, such as LGMD1B (now Emery-Dreifuss muscular dystrophy, or EDMD) and LGMD1E (now Myofibrillar Myopathy). For other LGMDs that still meet the requisite criteria, the consortium designated a new naming system as follows:
LGMD + inheritance pattern R(ecessive) or D(ominant) + order of discovery, affected protein. Examples: “LGMDR9” = FKRP-related LGMD or “LGMDR22” = Collagen VI-related LGMD (recessive Bethlem Myopathy).
Note that if the commonly used “LGMD” name has been changed, this does not mean a change in your diagnosis or treatment. It simply denotes a new way of classifying what experts have learned about your and related conditions. Affected individuals will continue to belong to a specific community and care standards will still apply.
Ultimately, this workshop achieved a much-needed update of the definition for LGMD and a new system for defining these conditions. The system ensures that LGMD is defined as a clear, distinct entity with several common denominators among subtypes, and also allows for future discoveries to be logically added.
What do you think? Cure CMD is happy to answer any questions you may have about the new LGMD nomenclature system and what your LGMD diagnosis is now called. And, we’d love to hear your thoughts about these changes. Please share in the comments section below.