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Diagnostic Testing Resources for FSHD
Yes. There is a DNA test for FSHD. It is highly reliable for most cases . The test detects the 4q35 DNA deletion described in the Genetics section of this website. Although several factors may occasionally complicate the test, confirmation of the 4q35 deletion is 98% reliable as a presumptive diagnosis of FSHD. The test requires no more than a small amount of blood that one’s physician sends to a testing laboratory. The laboratory extracts sufficient DNA for the test from the cells present in the blood. The FSH Society can provide information regarding the test and laboratories that currently offer it. It does not, however, endorse any test or laboratory. An individual should consult his or her physician and the laboratories about the DNA diagnostic test. Currently, there is no DNA test available for those relatively few cases where there is no linkage between FSHD and chromosome 4. What causes FSHD? The cause of FSHD is not yet precisely known. Scientists do have some pieces of the puzzle and more knowledge is being gained each year. The most important discovery to date is that FSHD is usually associated with a small DNA deletion on chromosome 4. How is the FSHD DNA test performed? DNA is analyzed using a method called Southern blotting. DNA, which is a very long molecule, is cut into small, measurable fragments. The size of the DNA fragments in the region of chromosome 4 that is important for the diagnosis of FSHD is measured. Individuals who have FSHD almost always have a DNA fragment that is unusually small, due to the deletion on chromosome 4. Is there an association between the size of the deletion on chromosome 4 and the severity of FSHD in an individual? There does appear to be a relationship between the size of the deletion and the severity and age of onset of FSHD. Large deletions (resulting in very small fragments) appear to be associated with earlier onset and more severe symptoms. Also, large deletions are more likely to be sporadic rather than inherited. Small deletions tend to be associated with later onset and milder symptoms. Is FSHD always associated with a deletion on chromosome 4? No. In about 2% of individuals who have symptoms of FSHD, no deletion is detected on chromosome 4. It is probable that these individuals have a different, unknown gene mutation on the same or another chromosome, which results in similar symptoms. How accurate is DNA testing for FSHD? About 98% of individuals with FSHD can be accurately diagnosed by the DNA test due to the detection of a deletion. In comparison, individuals in the general population without FSHD are extremely unlikely to show a deletion in the same region of chromosome 4. However, within some FSHD families, some individuals may be found who appear to have a deletion, but do not show obvious symptoms of FSHD. This situation is more likely to occur when the deletion is small. How is DNA obtained from an individual who has FSHD? DNA is isolated from white blood cells. A single tube of blood (about a tablespoon) provides enough DNA to perform the test. I have symptoms of FSHD. How can I arrange for a DNA test to confirm FSHD? You can ask your doctor to refer you to your local genetics clinic. There, a detailed family history will be taken. The geneticist will be able to identify those individuals in your family who could most benefit from DNA testing. The geneticist will also be able to arrange for the blood sampling and shipment of the blood to a testing center. The DNA test results are reported to the referring physician (usually a geneticist). Since DNA test results can be difficult to interpret and understand, it is essential to have a skilled professional, such as a geneticist, explain the results of DNA testing. What is meant by sporadic FSHD and inherited FSHD? Sporadic FSHD means a single individual in a family has FSHD, but no one else in the family has symptoms. It also means that the FSHD deletion was identified in the affected individual but not in his/her parents. Once someone is diagnosed with sporadic FSHD, the risk of transmitting FSHD is the same as in the inherited form of FSHD. Inherited FSHD means that the disease is present in multiple members of the family, over two or more generations. I have FSHD. What is the risk that I could have a child with FSHD? Individuals with FSHD have a 50% chance of having a child with FSHD in each pregnancy. We have been told that our child has sporadic FSHD. Is there any risk FSHD could occur in our next child? Up to 20% of apparently sporadic cases of FSHD arise due to mosaicism for the FSHD deletion in one parent. This means that one parent has a mixture of cells: some with the deletion and some without the deletion. This mixture of cells may or may not be detectable by the DNA test, depending upon the extent of mosaicism in the individual. Therefore, there is a risk of having another child with FSHD, even if there is no detectable deletion in either parent. Is there a prenatal test for FSHD? Yes. Using the same technology of the DNA test described above, prenatal testing is possible. An individual who is interested in a prenatal test for FSHD should consult his or her physician and the genetic testing laboratories. In prenatal diagnosis, fetal cells are obtained primarily by one of two procedures. The earliest procedure is called chorionic villus sampling (CVS). This procedure is performed at about the 10th to 12th week of the pregnancy. The alternative procedure is called amniocentesis. This procedure is performed at about the 15th to 16th week of the pregnancy. Individuals at risk of having a child with FSHD should see a geneticist for counseling as early as possible in the pregnancy, or even before becoming pregnant since it is necessary for their DNA to be tested in order to obtain accurate results. Prenatal diagnosis must be arranged many weeks in advance, through a genetics clinic. Prenatal tests have risks associated with them, and therefore it is important to obtain genetic counseling, and consider all the information about prenatal testing carefully before deciding to proceed. In general, molecular diagnostic laboratories make a special effort to process prenatal DNA samples as rapidly as possible. Is pre-implantation genetic diagnosis (PGD) available for FSHD? Yes. An important aspect to know about PGD is that the statistic mapping techniques are used to infer if the actual deletion that causes FSHD itself is inherited. A study is done on the inheritance pattern of map markers on each allele to ascertain whether the disease-carrying allele has been inherited. There are documented cases where the disease allele is inherited but the deletion of D4Z4 is not inherited due to rearrangement (e.g. the D4Z4 region comes from the other chromosome). With FSHD a prenatal diagnosis usually follows the PGD to be sure the deletion was not passed on. -Adapted from Marsha Speevak, Ph.D., Molecular Diagnostic Laboratory, Genetics DepartmentChildren's Hospital of Eastern Ontario, Ontario, Canada FSH Watch, Vol. 5 No. 1, Spring 1998 [amended Fall 2007]
Diagnostic Testing Labs and GeneClinics / GeneTests In North America, the University of Iowa, Children’s Hospital of Eastern Ontario, and Athena Diagnostics offer genetic testing. More complex genetic testing cases may require more scrutiny at other academic testing labs such as Leiden University. Note that the University of Iowa does A/B allele testing. • Alberta Children’s Hospital, Molecular Diagnostic Laboratory, Calgary, Alberta, Canada These are the contacts for several of the North American testing sites. University of Iowa Hospitals and Clinics Athena Diagnostics Inc Children's Hospital of Eastern Ontario TEXT SIZE
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FSH Society, Inc. • 64 Grove Street • Watertown, MA 02472 • Tel: 617 658-7878 • Fax: 617 658-7879
Is there a DNA test for FSHD?