Introduction

Limb girdle muscular dystrophy (LGMD) includes inherited muscular dystrophies grouped under the label "limb girdle" because they generally affect the pelvic and shoulder girdles. To date, over 20 types of LGMD have been identified, each caused by mutations in a different gene. Each subtype has specific features, such as age of onset of symptoms, rate of progression, particular muscles involved, and whether there is heart and respiratory involvement.
 
It is vital to go beyond the general diagnosis of LGMD and diagnose the patient’s particular LGMD subtype so that appropriate monitoring and therapy is conducted. Enrollment in most clinical trials will also require information of the patient’s specific type of LGMD.
 
Because a large number of genes cause LGMD and variable clinical presentation, determining the specific type of LGMD of a particular patient is challenging. We have therefore developed this online tool, which predicts the most likely type(s) of LGMD a patient may have, based on clinical presentation and laboratory findings. With current technology, complete sequencing of every LGMD gene is impractical; however, narrowing the number of types under consideration increases the likelihood of arriving at a specific molecular diagnosis. This tool helps the clinician determine which molecular diagnostic tests (protein or genetic sequencing) are most likely to be informative to reach the final diagnosis for a particular patient.
 
This subtype prediction tool is developed using a variety of data sources, including a thorough review of the medical literature on clinical presentations and diagnostic findings for various forms of LGMD, and consultation with diagnostic pathologists and clinical neurologists who specialize in research and diagnosis of muscular dystrophy.

Caveats

1. A diagnosis of LGMD is arrived at by a process of elimination. This tool assumes that the diagnostic exclusion of other, more common types of MD (Duchenne, Becker, Myotonic, FSH, etc.) was performed. In addition the tool assumes that neurogenic causes of muscular weakness (Spinal Muscular Atrophy, Charcot-Marie-Tooth, etc.), metabolic myopathies (Pompe, McArdle, etc.), and autoimmune causes of muscle weakness have already been considered and excluded.

2. Some types of LGMD present as distal muscular dystrophies.  Although, this tool considers one of the more common forms of distal muscular dystrophy, Nonaka Distal Myopathy (aka HIBM2), it does not consider all of the currently-identified types of distal MD.  A listing of currently-identified types of distal MD is given at http://neuromuscular.wustl.edu/musdist/distal.html.

3. New genetic types of LGMD continue to be identified.  It is estimated that with current knowledge, about 75% of LGMD patients are able to be diagnosed with a specific type. 

4. Even for currently-identified types of LGMD, a number of case reports in the medical literature describe patients whose phenotypes are atypical, or outside the previously-reported spectrum of their particular form of LGMD.  The tool may not be able to correctly diagnose patients whose symptoms are unusual or unreported for their type of LGMD.

5. The “gold standard” for diagnosis of a specific type of LGMD is identification of pathological mutations by genetic sequencing (on one allele for a dominant inheritance, on both alleles for a recessive inheritance).  In some cases, testing at the protein level is desirable before proceeding to genetic sequencing.  Thus, this tool’s output should be considered a recommendation for which genes or proteins to consider in further testing, and not a diagnosis in itself.

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