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7. How is FSHD Diagnosed?
The diagnosis of FSHD is made by a Neurologist based on the pattern of muscle weakness that is seen on bedside examination. An EMG (electromyography) may be helpful in certain cases but it only confirms the presence of a muscular dystrophy and cannot differentiate between the different muscular dystrophies. The diagnosis can then be confirmed on blood DNA test, a test which has an accuracy of about 95 %. Genetic testing for FSHD using a blood sample is commercially available only for FSHD1.
The genetic test consists of measuring the size of the DNA segment containing multiple copies of identical DNA sequences called repeats (Blue triangles in figure below). In the genetic testing process, molecular scissors (restriction enzymes) are used to cut the DNA on either side of the repeats. In healthy individuals both copies of chromosome 4 will have more than 10 copies of this repetitive sequence of DNA whereas in individuals with FSHD, one chromosome 4 will have only 1 and 9 copies. The readout from the genetic test gives two numbers, one from each copy of chromosome 4 (seen in red below) and corresponds to the size of the DNA segment, containing the repetitive sequences. An allele size of greater than 50 Kb represents a normal allele whereas an allele from someone with FSHD will be between 10 and 38 Kb.
As discussed previously patients with very large deletions, resulting in a small residual piece of DNA tend to have more severe disease. So typically, patients whose contracted segment of the repeats measures between 10-17Kb will predictably have more severe muscle weakness and are more likely to have hearing and retinal vascular complications. On the other hand, having a contracted repeat segment between 20-38 Kb does not tell you much about prognosis since such patient vary from very mild to severe regardless of the size of the segment within that range.
If the DNA is negative for the FSHD defect, there could be one of two possibilities. The first is that the person may look like they have FSHD but, in fact, have another muscular dystrophy. It is not an uncommon for one form of dystrophy to look like another in its clinical presentation. In such a case, further blood testing in addition to a muscle biopsy may be needed to arrive at the proper diagnosis. The second possibility is that the person does have FSHD but fall in the 5% of individuals with FSHD2. At present, commercial genetic testing for FSHD2 is not yet available to confirm this diagnosis in the United States.
For more information, please contact the Fields Center FieldsCenter@urmc.rochester.edu