Autopsy and Case Reports
Autopsy and Case Reports
Article / Clinical Case Report

A rare case of centronuclear myopathy with DNM2 mutation: genotype–phenotype correlation

Amir Ghorbani Aghbolaghi; Mirna Lechpammer

Downloads: 1
Views: 1461


Centronuclear myopathy (CNM) is a group of rare genetic muscle disorders characterized by muscle fibers with centrally located nuclei. The most common forms of CNM have been attributed to X-linked recessive mutations in the MTM1 gene; autosomal-dominant mutations in the DNM2 gene-encoding dynamin-2, the BIN1 gene; and autosomal-recessive mutations in BIN1, RYR1, and TTN genes. Dominant CNM due to DNM2 mutations usually follows a mild clinical course with the onset in adolescence. Currently, around 35 mutations of the DNM2 gene have been identified in CNM; however, the underlying molecular mechanism of DNM2 mutation in the pathology of CNM remains elusive, and the standard clinical characteristics have not yet been defined. Here, we describe the case of a 17-year-old female who presented with proximal muscle weakness along with congenital anomalous pulmonary venous connection (which has not been described in previous cases of CNM), scoliosis, and lung disease without a significant family history. Her creatine kinase level was normal. Histology, special stains, and electron microscope findings on her skeletal muscle biopsy showed CNM with the characteristic features of a DNM2 mutation, which was later confirmed by next-generation sequencing. This case expands the known clinical and pathological findings of CNM with DNM2 gene mutation.


University of California, Davis Medical Center, Department of Pathology and Laboratory Medicine. Sacramento, CA, USA.


1. Spiro AJ, Shy GM, Gonatas NK. Myotubular myopathy: persistence of fetal muscle in an adolescent boy. Arch Neurol. 1966;14(1):1-14. PMid:4954227.

2. Fardeau M. Skeletal muscle pathology. In: Mastaglia FL, Walton Sir JN, editors. Congenital myopathies. London: Churchill Livingston; 1982. p. 161-203.

3. Fardeau M, Tome F. Congenital myopathies. In: Engel AG, Franzini-Armstrong C, editors. Myology. 2nd ed. New York: McGraw Hill; 1994. p. 1500-25.

4. North KN. Congenital myopathies. In: Engel A, Franzini-Armstrong C, editors. Myology. 3rd ed. New York: McGraw Hill; 2004. p. 1473-533.

5. Toussaint A, Cowling BS, Hnia K, et al. Defects in amphiphysin 2 (BIN1) and triads in several forms of centronuclear myopathies. Acta Neuropathol. 2011;121(2):253-66. PMid:20927630.

6. Bohm J, Biancalana V, DeChene ET, et al. Mutation spectrum in the large GTPase dynamin 2, and genotype–phenotype correlation in autosomal dominant centronuclear myopathy. Hum Mutat. 2012;33(6):949-59. PMid:22396310.

7. Zanoteli E, Oliveira AS, Schmidt B, Gabbai AA. Centronuclear myopathy: clinical aspects of ten Brazilian patients with childhood onset. J Neurol Sci. 1998;158(1):76-82. PMid:9667782.

8. Laporte J, Hu LJ, Kretz C, et al. A gene mutated in X-linked myotubular myopathy defines a new putative tyrosine phosphatase family conserved in yeast. Nat Genet. 1996;13(2):175-82. PMid:8640223.

9. Bartsch O, Kress W, Wagner A, Seemanova E. The novel contiguous gene syndrome of myotubular myopathy (MTM1), male hypogenitalism and deletion in Xq28: report of the first familial case. Cytogenet Cell Genet. 1999;85(3-4):310-4. PMid:10449925.

10. Sutton IJ, Winer JB, Norman AN, Liechti-Gallati S, MacDonald F. Limb girdle and facial weakness in female carriers of X-linked myotubular myopathy mutations. Neurology. 2001;57(5):900-2. PMid:11552027.

11. Bevilacqua JA, Bitoun M, Biancalana V, et al. “Necklace” fibers, a new histological marker of late-onset MTM1-related centronuclear myopathy. Acta Neuropathol. 2009;117(3):283-91. PMid:19084976.

12. Romero NB. Centronuclear myopathies: a widening concept. Neuromuscul Disord. 2010;20(4):223-8. PMid:20181480.

13. Pierson CR, Tomczak K, Agrawal P, Moghadaszadeh B, Beggs AH. X-linked myotubular and centronuclear myopathies. J Neuropathol Exp Neurol. 2005;64(7):555-64. PMid:16042307.

14. Nicot AS, Toussaint A, Tosch V, et al. Mutations in amphiphysin 2 (BIN1) disrupt interaction with dynamin 2 and cause autosomal recessive centronuclear myopathy. Nat Genet. 2007;39(9):1134-9. PMid:17676042.

15. Claeys KG, Maisonobe T, Böhm J, et al. Phenotype of a patient with recessive centronuclear myopathy and a novel BIN1 mutation. Neurology. 2010;74(6):519-21. PMid:20142620.

16. Jungbluth H, Zhou H, Sewry CA, et al. Centronuclear myopathy due to a de novo dominant mutation in the skeletal muscle ryanodine receptor (RYR1) gene. Neuromuscul Disord. 2007;17(4):338-45. PMid:17376685.

17. Bevilacqua JA, Monnier N, Bitoun M, et al. Recessive RYR1 mutations cause unusual congenital myopathy with prominent nuclear internalisation and large areas of myofibrillar disorganisation. Neuropathol Appl Neurobiol. 2011;37(3):271-84. PMid:21062345.

18. Ceyhan-Birsoy O, Agrawal PB, Hidalgo C, et al. Recessive truncating titin gene, TTN, mutations presenting as centronuclear myopathy. Neurology. 2013;81(14):1205-14. PMid:23975875.

19. Jeannet PY, Bassez G, Eymard B, et al. Clinical and histologic findings in autosomal centronuclear myopathy. Neurology. 2004;62(9):1484-90. PMid:15136669.

20. Bitoun M, Maugenre S, Jeannet P-Y, et al. Mutations in dynamin 2 cause dominant centronuclear myopathy. Nat Genet. 2005;37(11):1207-9. PMid:16227997.

21.National Center for Biotechnology Information – NCBI [cited 2016 Sept 26]. Available from:

Publication date:

59550d870e88256f5224dc1f autopsy Articles
Links & Downloads

Autops Case Rep

Share this page
Page Sections