Neuropediatrics 2013; 44 - PS17_1265
DOI: 10.1055/s-0033-1337830

Divergence in clinical presentation of Dynamin2-caused centronuclear myopathy is associated with mutations in distinct parts of the DNM2 gene

E Hobbiebrunken 1, C Bönnemann 2, C Müller-Reible 3, E Wilichowski 1
  • 1Abteilung Neuropädiatrie, Klinik für Kinder- und Jugendmedizin, Göttingen, Germany
  • 2Porter Neuroscience Research Center, Bethesda, United States
  • 3Institut für Humangenetik, Biozentrum Am Hubland, Würzburg, Germany

Centronuclear myopathy (CM) is a heterogeneous group of congenital myopathies with onset from birth to adult ages. Autosomal recessive CM is caused by RYR1 and BIN1 (Amphiphysin) gene mutations, whereas Dynamin2 (DNM2) mutations cause dominant CM.

We present the two patients with different clinical courses who carry DNM2 mutations in different parts of the gene.

Case report 1: A 6-year-old boy was born to healthy nonconsanguine parents. He showed marked generalized muscular hypotonia and muscle weakness after birth resulting in feeding difficulties. Motor development was severely retarded with unsupported siting since the age of 2 years and walking since the age of 3 years. Muscle strength is still continuously improving. Muscle biopsy showed centralized nuclei with type 1 fiber predominance. DNM2 gene analysis revealed de novo heterozygous mutation in exon 17: c.1856 C>T, p.Ser619Leu.

Case report 2: A 20-year-old boy was born to healthy nonconsanguine parents. Motor development was normal until the age of 2 years when muscle weakness became increasingly evident. The clinical course was slowly progressive with scoliosis since the age of 12 years and loss of ambulation at the age of 17 years. At the age of 20 years, the wheelchair bound patient suffered from acute cardiopulmonary arrest and died in a persistent vegetative state. Muscle biopsy showed centralized nuclei, atrophy of type 1 fibers predominance. DNM2 gene analysis revealed de novo heterozygous mutation in exon 8: c.1102G>A, p.Glu368Lys.

Both case reports demonstrate the broad range of clinical manifestation of CM. Although case 1 shows the distinct features of the neonatal onset of a DNM2-related CM with continuously improving of muscle strength, the clinical course of the second case is rather classical. Exploration of gene databases resulted in a clear association between clinical courses and localization of the mutation within the DNM2 gene.