Type 2B ovelap: Characterization of the muscle involvement in dynamin 2-related

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Brain. 2006 Apr 3

Characterization of the muscle involvement in dynamin 2-related

centronuclear myopathy.

Fischer D, Herasse M, Bitoun M, Barragan-Campos HM, Chiras J, Laforet

P, Fardeau M, Eymard B, Guicheney P, Romero NB.

Institut National de la Sante et de la Recherche Medicale U582,

Institut de Myologie, IFR14, Groupe Hospitalier Pitie-Salpetriere,

Paris, France; Muskellabor, Department of Neurology, University of

Bonn, Germany.

Centronuclear myopathy (CNM) is a slowly progressive congenital

myopathy characterized by abnormal centrally located nuclei in a

large number of muscle fibres. Recently, different missense mutations

affecting the middle domain of the dynamin 2 (DNM2) have been shown

to cause autosomal dominant CNM. In order to better define the

phenotype of DNM2-related CNM, we report here on the clinical and

muscle imaging findings of 10 patients harbouring DNM2 mutations.

DNM2-CNM is characterized by slowly progressive muscular weakness

usually beginning in adolescence or early adulthood. In addition to

bilateral ptosis, our data show that distal muscle weakness often

exceeds proximal involvement. Furthermore, electrophysiological

investigations frequently demonstrated signs of mild axonal

peripheral nerve involvement, and electromyographical examination may

show neuropathic changes in addition to the predominant myopathic

changes.

These features overlap with findings seen in the phenotype of DNM2-

related autosomal dominant Charcot-Marie-Tooth disease type 2B. In

all 10 DNM2-CNM patients, muscle computer tomography assessment

showed a consistent pattern of muscular involvement and a

characteristic temporal course with early and predominant distal

muscle involvement, and later affection of the posterior thigh

compartment and gluteus minimus muscles. The recognition of this

specific imaging pattern of muscle involvement--distinct to the

reported patterns in other congenital myopathies--may enable a better

selection for direct genetic testing.