Inclusion Body Myopathy 2

Inclusion body myopathy 2 (IBM2) is an inherited disorder that is caused by lack of a bifunctional enzyme UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase. This disorder primarily affects skeletal muscles, which are necessary for body movement. Affected individuals begin to have muscle weakness in the lower legs in the late teens or early adult years. The weakness continues to deteriorate over time and eventually spreads to the hands, thighs, hips, and shoulders. Muscle weakness makes walking increasingly difficult, and affected people usually lose the ability to walk within 20 years after symptoms appear. Intellect is unaffected by IBM2 but effect on life expectancy is unknown. There is no cure for IBM2; however medical surveillance and care may help to improve some symptoms and overall condition of life. IBM2 is caused by pathogenic variants in the GNE gene.

IBM2 is inherited in an autosomal recessive manner. This type of inheritance requires the presence of two copies of a pathogenic variant in the gene for a person to have the genetic disease. Both parents must be carriers of a pathogenic variant in the gene in order to be at risk to have an affected child. The child must inherit a pathogenic variant from each carrier parent in order to be affected. There is a 1 in 4 chance that a baby will inherit two mutated copies of the gene and be affected when both parents are carriers.

There are generally no signs or symptoms associated with being a carrier for IBM2. However, the risk to have a child affected with IBM2 is increased. Testing of reproductive partners is recommended for carriers of IBM2.

IBM2 affects people worldwide. It is most frequent in Iranian Jewish decent estimated to affect 1 in 500 to 1,000 newborns. Individuals affected with this condition have also been reported in Japan, Italy and other ethnic groups.

Genetics Home Reference: Inclusion body myopathy 2 (http://ghr.nlm.nih.gov/)
Genetic Alliance: Inclusion body myopathy 2 (http://www.diseaseinfosearch.org/)

OMIM [IBM2: 600737, 605820, 269921, 603824] (http://www.ncbi.nlm.nih.gov/omim)
Gene Reviews: GNE-related myopathy (http://www.ncbi.nlm.nih.gov/books/NBK1262/)

• Full gene sequencing