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  • Genetics of Myotonic Dystrophy and FSHD
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Genetics of Myotonic Dystrophy and FSHD

The myotonic dystrophies (type I and type 2) and FSHD are autosomal dominant genetic disorders. If one parent has the affected gene, each child has 50% chance of inheriting the disorder. The gender of the child does not change the likelihood of inheriting the condition. If a child does not receive the abnormal gene, they will not develop or pass on the disease.

There are genetic tests available for DM1, DM2, and FSHD for adults as well as prenatal and preimplantation diagnosis.

Genetic Testing for FSHD

Facioscapulohumeral muscular dystrophy (FSHD) is a genetic condition that results from a DNA mutation. The mutation is a DNA deletion or a decrease in the amount of DNA that is normally present on a chromosome. There is a genetic test available for FSHD, although it is still unknown how the mutation results in FSHD or which genes are affected.

The genetic test for FSHD locates and measures the size of DNA deletion on chromosome 4. DNA is extracted from the blood sample and a chemical is used to break the DNA into smaller sections. The sections are placed into a gel with an electrical current that causes the pieces of DNA to move through the gel based upon their size. The size of the sections of DNA are compared to pieces of a known size. The test has a 95% rate of accuracy in detecting a genetic mutation. It should be noted that approximately 5% of individuals that have the clinical symptoms of FSHD do not have the DNA deletion on chromosome 4.

Condition	Size of DNA Deletion (in kilobase pairs)
Normal	Greater than 51 base pairs
Borderline	Between 36 and 50 base pairs
Affected	Less than 35 base pairs

 

There are three possible outcomes for this test. The presence of the DNA deletion indicates that the person will likely develop some symptoms of FSHD during their life; although approximately 5% of individuals with the deletion do not develop symptoms. Research has shown an association between the size of the DNA deletion and the severity of FSHD symptoms.

If the deletion is not detected, it indicates that the individual has not inherited the condition. They will not develop symptoms of FSHD nor will they pass the gene onto their children. It is important to note that 5% of individuals diagnosed with FSHD, do not have a deletion on chromosome 4. There is also the possibility of receiving inconclusive results if the size of the DNA deletion is between the normal and abnormal ranges. In general, this person will not develop FSHD although there is a possibility that their children may develop the disease.

Genetic Testing for Myotonic Dystrophy Type 1

Myotonic Dystrophy is a genetic condition that results from a DNA mutation. The mutation is a DNA expansion or an increase in the amount of DNA that is normally located on a chromosome. The additional DNA is located on chromosome 19. The mutation affects the gene for dystrophia myotonica protein kinase (DMPK) that results in abnormal clumps inside individual cells, which prevents cells in muscles and other tissues from functioning normally. Within the DMPK gene there is a section of DNA that contains a repeated sequence of three DNA nucleotide bases, CTG. It is not uncommon to have a small number of CTG repeats within the DMPK gene; too many repeats will result in a disruption of cellular functioning.

The genetic test for DM locates the specific area on chromosome 19 and measures the size of the DNA expansion. This test has nearly a 100% rate of accuracy in detecting the genetic mutation.

Condition	Size of DNA Deletion (in CTG repeats)
Normal	Less than 38 repeats
Borderline	Between 39 and 49 repeats
Affected	Mild 50 to approximately 150 Classic approximately 100 to 1000 Congenital greater than 2000

 

There are three possible outcomes for this DNA test. A positive result confirms the presence of the inherited DNA expansion. Positive test results indicate that a person will develop some symptoms of DM during their life. There is a relationship between the size of the expansion and the age of onset and severity of Myotonic dystrophy.

A negative test result indicates that a person has not inherited the DNA expansion. They will not develop symptoms of DM nor will they pass the gene onto their children. There is also the possibility of receiving inconclusive results if the size of the DNA expansion is between the normal and abnormal ranges. In general, the person will not develop DM but still has the chance of passing the mutation to their children.

Genetic Testing for Myotonic Dystrophy Type 2

Myotonic Dystrophy type II is a genetic condition that results from a mutation in your DNA. The mutation referred to as a DNA expansion is an increase in the amount of DNA that is normally located on a chromosome. The additional DNA is located on chromosome 3. The mutation affects the gene for zinc finger protein 9 (ZnF9) which prevents cells in muscles and other tissues from functioning normally. Within the ZnF9 gene there is a section of DNA that contains a repeated sequence of four DNA nucleotide bases, CCTG. It is normal to have a small number of CCTG repeats within gene. If there are too many repeats it will affect various cell functions.

The genetic test for DM II is designed to isolate and measure the size of the DNA expansion on chromosome 3. This test has nearly a 100% rate of accuracy in detecting the genetic mutation.

Condition	Size of DNA Deletion (in kilobase pairs)
Normal	Less than 175 base pairs
Borderline	Between 177-372 base pairs
Affected	Greater than 372 base pairs

*The number of CCTG base pairs in affected individuals averages approximately 20,000. There are three possible outcomes for this DNA test. A positive result confirms the presence of the inherited DNA expansion. Positive test results indicate that a person will develop symptoms of DM type II during their life. A negative test results indicates that a person has not inherited the DNA expansion. They will not develop symptoms of DM nor will they pass the gene on to their children. There is also the possibility of receiving inconclusive results if the size of the DNA expansion is between the normal and abnormal ranges. In general, the person will not develop DM but may still have the chance of passing the mutation to their children.

 

Last Reviewed and Updated 05/29/2009