About Centronuclear Myopathy

            MTM1         DNM2    RYR1    BIN  TTN (&RYR1)

General

Centronuclear myopathies belong to the congenital (genetic) muscle conditions. They have in common that the cell nuclei are not located at the edge but in the center of the muscle fibers.

What Muscle conditions belong to the centronuclear myopathies?

  • the x-chromosomal recessive type localized in the MTM1 gene (myotubular myopathy)
  • the autosomal dominant type localized in the DNM2 gene; and
  • die autosomal recessive types localized in the Titin, BIN1 oder RYR1 genes

IMG_0936Other even more rare gene mutations exist that are  also linked with centronuclear myopathies (MYF6, MTMr14, CCDC78). All these conditions have in common a general non advancing muscle weakness, albeit with highly variable characteristics even with one mutation type.

Due to the mutation, the enzyme, the is encoded by the gene, is built inaccurately or even not at all (e. g. for MTM1 myotubularine). The lacking of the enzyme leads to construction failures in the muscle and thus to a muscle weakness (e.g. myotubular myopathy).

How common is which of the centronuclear myopathies?

This is a tough question. At the IGBMC, where Jocelyn Laporte and Johann Böhm work, about  700 patients were examined  during the years 2000 – 2015. For most, mutations were found in the following genes:
400 in MTM1, 100 in DNM2, 20 in RYR1, 10 in BIN1, 10 in TTN
For 160 patients no mutation in any of these genes could be found.

What is the difference between central nuclear Myopathy and central core Myopathy?

CCM2
Source: J. Böhm

very short:
In the muscle biopsy of a centronuclear myopathy (left) centralized nuclei are visible. Normally they should be at the edge of the muscle fibers.
With a certain selective staining, in the muscle biopsy of a central core myopathy (right) a with stain (core) in the center of the muscle fiber becomes visible. This is because of the lacking of mitochondria (the power plants of the cell).

Certain mutations (e. g. in RYR1) can cause both pictures!

For more detailed and more exact information please read  the small essay of Johann Böhm.

More Information:

Sources:

-Facts about Genetics and Neuromuscular Diseases – 2011 MDA

-Pathogenic mechanisms in centronuclear myopathies – 2014 Heinz Jungbluth and Mathias Gautel

-personal communication Johann Böhm, IGBMC, 2015