Why is a genetic diagnosis important?
Limb girdle muscular dystrophy (LGMD) and Miyoshi Myopathy encompasses a number of different inherited muscular dystrophies that are grouped under the label of either "limb girdle" because they generally affect the pelvic and shoulder girdles or “miyoshi” because they generally affect the lower part of the limbs, particularly the leg. To date, over 25 different types of LGMD and 3 different types of Miyoshi have been identified, each one caused by mutations in a different gene. Each subtype has some specific features, such as age of onset of symptoms, rate of progression, particular muscles involved, and whether there is heart and respiratory involvement. These differences should be used to define the most appropriate standard of care and disease management among the different subtypes of LGMDs. It is therefore vital to go beyond the general diagnosis of LGMD or Miyoshi and determine the specific type involved in order to determine the best way to manage your disease. Subtyping LGMD and Miyoshi is done by gathering information such as family history, clinical presentation including CK levels, immunostaining of muscle biopsy and most importantly, genetic testing.
The Jain Foundation has partnered with several other LGMD family foundations to offer free genetic testing for patients suffering from muscular dystrophy to obtain a definitive and specific genetic diagnosis. Currently we are only able to offer the free genetic testing to those living in the US, but we hope to eventaully expand internationally. If you live within the US, please visit lgmd-diagnosis.org for more information. If you live in India, please contact in individuals listed here. For patients in other countries, we encourage you to take the eligibility quiz at lgmd-diagnosis.org, so that we can contact you quickly if we are able to expand internationally and offer free genetic sequencing in your country. In addition, please refer to our lists of diagnostic resources and physician referrals as these may be useful for those diagnosed with LGMD/Miyoshi or other forms of muscular dystrophy.
Below are specific reasons why determining the specific sub-type of LGMD or Miyoshi through the use of genetic analysis is important:
Differences in disease management
Among the different types of LGMD and Miyoshi, there are different types of disease presentation, with important implications for management. Prognosis for LGMD/Miyoshi is not uniform and therefore timely intervention through early identification of potential complications may improve survival. For example, the risks of cardiomyopathy and pulmonary problem varies greatly among the different forms of LGMD, with these issues being frequent in LGMD 2I patients, while very uncommon in LGMD2A or 2B patients. Also, anecdotal reports of prednisone use in LGMD/Miyoshi show striking differences among subtypes with prednisone seemly beneficial for LGMD2I patients, while negative effects have been reported when this treatment was offered to LGMD2B/Miyoshi patients.
Some potential treatments are mutation-specific
There are some new treatments currently under trials that would benefit patients only with some specific types of mutations (i.e. stop-codon read-through approaches that would only benefit patients with a non-sense mutation). It is thus important to know your specific type of mutation in order to assess whether or not these treatments could be beneficial to you.
Participation in clinical trials
At least half of ongoing clinical trials for these diseases are sub-type specific. Moreover, clinical trials often need the mutation information as a pre-requisite for enrollment.
Collection of disease specific information
In order to obtain a greater understanding of how each disease progresses, it is important to gather specific information on each individual sub-type. One such example is the International Clinical Outcome Study for Dysferlinopathy (LGMD2B/Miyoshi).