Limb girdle muscular dystrophies (LGMD) are inherited muscular dystrophies grouped under the label "limb girdle" because they generally affect the pelvic and shoulder girdles.
To date, over 30 types of LGMD are identified, each caused by mutations in a different gene. New subtypes continue to be discovered, so the current list is almost certainly incomplete. 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. Because a large number of genes cause LGMD and variable clinical presentation, determining the specific type of LGMD of a particular patient is challenging.
It is vital for appropriate subtype specific monitoring (for example, cardiac or respiratory involvement in some subtypes) and any available therapy. Enrollment in clinical trials also requires information of the patientís specific type of LGMD.
The tool predicts the most likely type(s) of LGMD a patient may have, based on clinical presentation and laboratory findings.
This subtype prediction tool was 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.
ALDA assumes that the patient has one of the diseases included in the tool and will give a predicted percentage even if the patient has none of the listed diseases. Therefore, if the concordance score is medium-low or low, the patient may not have one of the listed diseases. In addition the tool assumes that neurogenic causes of muscular weakness (Spinal Muscular Atrophy, Charcot-Marie-Tooth, etc.) and autoimmune causes of muscle weakness have already been considered and excluded.
Some types of LGMD present as distal muscular dystrophies. Although, this tool considers one of the more common forms of distal muscular dystrophy, GNE Myopathy (aka Nonaka Distal Myopathy or 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
ALDA only evaluates for 27 LGMD subtypes, plus other muscular dystrophies which have overlapping clinical presentations such as Becker/DMD manifesting carriers, FSHD, Pompe, X-linked EDMD, and GNE myopathy. New genetic types of LGMD continue to be identified but aren’t included or evaluated by ALDA. It is estimated that with current knowledge, about 75% of LGMD patients are able to be diagnosed with a specific type. 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.
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.
This tool is intended for use by trained clinicians. Its output is based on the typical clinical and laboratory findings for different genetic types of Limb-Girdle Muscular Dystrophy as described in the medical literature. The output is limited by the current state of knowledge, and no guarantees are made for its accuracy. The output of this tool is not a substitute for the physicianís medical judgment, or appropriate clinical evaluation and diagnostic tests.
For technical issues please email lgmdtool@jain-foundation.org