Myotubular myopathy

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Classification according to ICD-10
G71.2 Congenital myopathies
myotubular (centronuclear) myopathy
ICD-10 online (WHO version 2019)

As centronuclear myopathy or centronuclear myopathy a family is rare muscular diseases from the group of congenital myopathies referred, which was first described in 1966.

clinic

Clinically, three types of disease can be distinguished, which also differ in terms of their inheritance :

  • The X-linked recessive form has the most severe course. The affected boys have generalized hypotonia of the muscles at birth (“ floppy infant ”); motor development is significantly delayed. Problems caused by weak respiratory muscles in particular lead to death in the first few months of life. Mothers who are heterozygous for the genetic defect can, as carriers, have a mild weakness of the facial muscles or a low level of myotonia .
  • The autosomal dominant form is characterized by slowly progressive muscle weakness that occurs during childhood or young adulthood. A proximal distribution pattern is typical, mainly affecting the muscles of the neck, shoulder girdle and trunk. Ocular muscle involvement with ptosis and external ophthalmoplegia is common .
  • The rare autosomal recessive form has a heterogeneous course. The onset of the disease lies between the two other forms.

histology

Typical histology with centralized nuclei.

In the muscle biopsy , immature muscle fibers with a large number of central nuclei are noticeable in all forms, the histological picture of which is reminiscent of the fetal myotubular development stage of the skeletal muscles.

genetics

In the case of the X-linked recessive form, mutations of the MTM1 gene coding for the phosphatase myotubularin have been described in the majority of families . While mutations of the DNM2 gene coding for the GTPase Dynamin-2 were detected in individual families in the autosomal dominant form, mutations in the BIN1 gene were found in the autosomal recessive form. Interestingly, this gene appears to play a key role in normal skeletal muscle development.

Individual evidence

  1. ^ Spiro et al: Myotubular myopathy. In: Arch Neurol 1966; 14, pp. 1-14. PMID 4954227
  2. ↑ De Angelis et al .: Centronuclear myopathy: clinical, morphological and genetic characters. A review of 288 cases. In: J Neurol Sci. 1991; 103 (1), pp. 2-9. PMID 1865227
  3. ↑ Heckmatt et al: Congenital centronuclear (myotubular) myopathy: a clinical, pathological and genetic study in eight children. In: Brain. 1985; 108, pp. 941-964 PMID 4075080
  4. ^ Wallgren-Pettersson et al.: The myotubular myopathies: differential diagnosis of the X linked recessive, autosomal dominant, and autosomal recessive forms and present state of DNA studies. In: J Med Genet. 1995; 32, pp. 673-679 PMID 8544184
  5. ↑ Laporte ua: A gene mutated in X-linked myotubular myopathy defines a new putative tyrosine phosphatase family conserved in yeast. In: Nat Genet . 1996; 13 (2), pp. 175-182. PMID 8640223
  6. ↑ Nicot et al .: Mutations in amphiphysin 2 (BIN1) disrupt interaction with dynamin 2 and cause autosomal recessive centronuclear myopathy. In: Nature Genet. 200; 39, pp. 1134-1139. PMID 17676042
  7. ↑ Wechsler-Reya et al .: A role for the putative tumor suppressor Bin1 in muscle cell differentiation. In: Mol Cell Biol. 1998; 18 (1), pp. 566-575. PMID 9418903

literature

  • H. Jungbluth, C. Wallgren-Pettersson, J. Laporte: Centronuclear (myotubular) myopathy. In: Orphanet J Rare Dis. 2008 Sep 25; 3, p. 26. PMID 18817572 , PMC 2572588 (free full text)

Web links

  • ZNM - Strong together! e. V .: This association, founded in 2015, represents those affected by myotubular and other centronuclear myopathies and their relatives. He organizes annual meetings in Germany for the families affected and the scientists researching a cure.
  • mtmx.de: This voluntary contact point and self-help group for families of children with myotubular myopathy, founded in 2008, publishes information and has been organizing annual meetings for families since 2009.
  • Bottom at orpha-selbsthilfe.de (support group for people with rare diseases)
  • Entry in the Orphanet