An overview of myotubular and centronuclear myopathy, by Dr Meriel McEntergert:

The myotubular and centronuclear myopathies belong to a group of conditions known as the Congenital Myopathies. These are inherited muscle disorders distinguished by specific structural changes seen within the muscle on histopathological (microscopic) examination. The characteristic feature in the case of the myotubular/centronculear myopathies is the presence of the nucleus in the centre of the muscle fibre instead of the usual position at the edge. In the first description of a family with this condition by Spiro and colleagues in 1966 the term myotubular myopathy was proposed. They considered that the disease resulted from maturational arrest in the fetal stage of muscle development as the histological findings were thought to resemble developing fetal muscle when fetal myotubes are present. Sher and colleagues described a further family with the condition the following year but preferred the term centronculear myopathy. With further clinical descriptions it has become clear that there are 3 forms of the condition distinguished by inheritance pattern and variation in the severity of symptons. They are

1) Congenital X-linked Recessive (OMIM 310400)
2) Congenital Autosomal Recessive (OMIM 255200)
3) Autosomal Dominant (OMIM 160150)

The term Myotubular Myopathy has been retained for the x linked recessive form while centronuclear myopathy is generally used to refer to the autosomal forms. The genes causing all three forms have now been identified following genetic linkage analysis studies in affected families. The gene for the x linked recessive form, which is the most common form, was identified first (1996) and the genes for the autosomal forms which are rarer, were identified approximately 10 years later. The function of these genes is currently unclear. Early research findings suggest they may play a role in the normal folding of membranes that form various components of the muscle cell. One or more further genes that cause centronuclear myopathy have yet to be identified as not everyone affected by the condition has a change in one of these 3 genes.

1) X linked - Myotubularin (MTM1) OMIM 300415
2) Autosomal Recessive - Amphysin II (BIN) OMIM 601248
3) Autosomal Dominant - Dynamin 2 (DNM2) OMIM 602378

References: Spiro AJ, Shy GM, Gonatas NK Myotubular myopathy Archives of Neurology 1966 14:1-14
Sher JH, Rimalovski AB , Athanassiades TJ, Aronson SM Familial centronuclear myopathy: a clinical and pathological study Neurology 1967 ( Minneapolis ) 17: 727-742
Laporte J, Hu LJ, Kretz C, Mandel J, Kiochis P, Coy JF, Klauck SM, Poustka A, Dahl N. 1996 A gene mutated in X-linked myotubular myopathy defines a new putative tyrosine phosphatase family conserved in yeast Nat Genet. 1996 13: 175-182

Recent publications in the field of myotubular myopathy and centronuclear myopathy:

Nicot AS, Toussaint A, Tosch V, Kretz C, Wallgren-Pettersson C, Iwarsson E, Kingston H, Garnier JM, Biancalana V, Oldfors A, Mandel JL,
Laporte J.
Mutations in amphiphysin 2 (BIN1) disrupt interaction with dynamin 2 and cause autosomal recessive centronuclear myopathy.
Nat Genet. 2007 Sep;39(9):1134-9 . Epub 2007 Aug 5

Bitoun M, Maugenre S, Jeannet PY, Lacène E, Ferrer X, Laforêt P, Martin JJ, Laporte J, Lochmüller H, Beggs AH, Fardeau M, Eymard B,
Romero NB, Guicheney P.
Mutations in dynamin 2 cause dominant centronuclear myopathy.
Nat Genet. 2005 Nov;37(11):1207-9 . Epub 2005 Oct 16.

Jungbluth H, Zhou H, Sewry CA, Robb S, Treves S,Bitoun M, Guicheney Pf, Buj-Bello A, Bönnemann C, Muntoni F.
Centronuclear myopathy due to a de novo dominant mutation
in the skeletal muscle ryanodine receptor (RYR1) gene
Elsevier Publishing 2007. (Courtesy of Elsevier Publishing and Science Direct)

Buj-Bello A, Fougerousse F, Schwab Y, Messaddeq N, Spehner D, Pierson C R, Durand M, Kretz C, Danos O, Douar AM, Beggs A,Schultz P,
Montus M, Denèfle P, Mandel JL
AAV-mediated intramuscular delivery of myotubularin corrects the myotubular myopathy phenotype in targeted murine muscle and suggests a function in plasma membrane homeostasis.
Journal: Human molecular genetics, 2008 Apr 22; [Epub ahead of print]