FAQ: Diagnosis, Prognosis, Progression, and Inheritance

Click on the questions below to see the answers.

How is LGMD2B/Miyoshi/dysferlinopathy diagnosed?

Diagnosis is generally made based on the following information:

 

  • A detailed patient and family history (a 3 generation pedigree)
  • The source of the muscle weakness (nerve or muscle)
  • A detailed examination to look for specific symptoms of LGMD2B or Miyoshi (jump to FAQ on LGMD2B/Miyoshi/Dysferlinopathy)
  • Muscle biopsy analysis to look for the presence of dysferlin protein
  • Blood (monocyte) testing to look for the presence of dysferlin protein
  • Genetic testing (sequencing of the dysferlin gene, also called mutational analysis) to identify disease-causing mutations in dysferlin (jump to FAQ on proteins, DNA, and mutations for more information on types of mutations and the benefits of gene mutation analysis)
If I have LGMD2B/Miyoshi, will my children inherit it?

All of the muscle diseases associated with dysferlin deficiency have an autosomal recessive inheritance, so a person will only have symptoms if he/she inherits a mutated version of the dysferlin gene from both parents. Children of someone with Dysferlinopathy/LGMD2B/Miyoshi will definitely be a carrier of one dysferlin mutation because each child inherits one of their dysferlin genes from the affected parent who carriers a dysferlin mutation on each of their copies of the dysferlin gene.  In the absence of a spontaneous mutation, the children of an affected individual will only develop symptoms if they inherit a second mutated dysferlin gene from the other unaffected parent. Based on the incidence of these conditions in the general population, there are probably only about 3-5 people out of every thousand who have one copy of a mutated dysferlin gene (carriers). So, the chance of children inheriting these conditions is quite small unless the other unaffected parent has a family history of these conditions or shares a common ancestry with the affected parent.

 

If both parents have one copy of a mutated dysferlin gene, each child has a 25% chance of getting both defective copies and thus the disease. However, for each child of this same couple there is also a 50% chance of being a carrier of the defective gene, meaning that he/she has a single mutated copy of the gene but does not show any symptoms. Genetic testing in families with recessive disorders is sometimes advisable in order to detect carriers. It might also be good to determine whether the potential spouses of carriers or affected individuals are also carriers. Determination of a person's carrier status requires testing his/her DNA (rather than antibody testing for the dysferlin protein), since a carrier still expresses dysferlin protein from their good copy of the dysferlin gene.

What is autosomal recessive inheritance?

A single defective dysferlin gene cannot cause LGMD2B/Miyoshi. For the disease to occur, both copies of the dysferlin gene must be defective. Dysferlin is autosomal. This means that it is not a sex-linked gene, and both males and females are affected with the same frequency. One copy of the gene is inherited from each parent. If one good copy and one defective copy are inherited, the single good copy is sufficient for normal muscle function and the individual is only a "carrier" of the disease. If both parents are carriers, each child has a one in four (25%) chance of inheriting two defective copies of dysferlin and developing LGMD2B/Miyoshi.

What is the prognosis and rate of progression for LGMD2B/Miyoshi?

The rate of progression of LGMD2B/Miyoshi is fairly slow compared to most other types of muscular dystrophy. Among the identified forms of LGMD, type 2B is one of the more slowly progressive forms. There have been some reports that Miyoshi has a slower progression than LGMD2B, while other reports indicate that the two are similar. This may reflect a difference in the initial muscles affected, since weakness in the calf muscles has less impact on a patient's function than weakness in the hip muscles. However, the reported rates of progression and symptoms do vary significantly, which may be due to differences in the type of mutation or other genetic differences between populations studied. There have not been any reports of cardiomyopathy (dystrophy of the heart muscle) in either LGMD2B or MM, nor have there been any reports that either condition significantly shortens life expectancy.

Does LGMD2B/Miyoshi have any impact on respiratory function?

Coming soon.

Is there an effect of exercise on the progression of LGMD2B/Miyoshi muscle weakness?

Coming soon.