Download PDF
J Pediatr Genet 2022; 11(04): 304-308
DOI: 10.1055/s-0040-1718724
Case Report

Duchenne Muscular Dystrophy and Early Onset Hypertrophic Cardiomyopathy associated with Mutations in Dystrophin and Hypertrophic Cardiomyopathy-Associated Genes

Liam Aspit  ‡   *
1   The Shraga Segal Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel
2   The National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer Sheva, Israel
,
Noga Arwas  ‡   *
3   Department of Pediatric Cardiology, Soroka University Medical Center and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel
,
Hanna Krymko
3   Department of Pediatric Cardiology, Soroka University Medical Center and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel
,
Yoram Etzion 
4   Department of Physiology and Cell Biology, Faculty of Health Sciences and Regenerative Medicine and Stem Cell Research Center, Ben-Gurion University of the Negev, Beer Sheva, Israel
,
Ruti Parvari    *
1   The Shraga Segal Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel
2   The National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer Sheva, Israel
,
Aviva Levitas  ‡   *
3   Department of Pediatric Cardiology, Soroka University Medical Center and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel
› Author Affiliations Funding This study was supported by The Israeli Ministry of Science, Technology and Space (to R.P.) and Ben-Gurion University of the Negev, Faculty of Health Sciences (to A.L.).
› Further Information
    Permissions and Reprints

Abstract

Duchenne muscular dystrophy (DMD) is a progressive muscular damage disorder caused by mutations in dystrophin gene. Cardiomyopathy may first be evident after 10 years of age and increases in incidence with age. We present a boy diagnosed at 18 months with a rare phenotype of DMD in association with early-onset hypertrophic cardiomyopathy (HCM). The cause of DMD is a deletion of exons 51–54 of dystrophin gene. The cause of HCM was verified by whole exome sequencing. Novel missense variations in two genes: MAP2K5 inherited from the mother and ACTN2 inherited from the father, or de novo. The combination of MAP2K5, ACTN2, and dystrophin mutations, could be causing the HCM in our patient. This is the second patient diagnosed, at relatively young age, with DMD and HCM, with novel variations in genes known to cause HCM. This study demonstrates the need for genetic diagnosis to elucidate the underlying pathology of HCM.

Keywords

Duchenne muscular dystrophy - hypertrophic cardiomyopathy - MAP2K5 - ACTN2

* These authors contributed equally to this work.


Supplementary Material



Publication History

Received: 24 June 2020

Accepted: 12 September 2020

Article published online:
19 November 2020

© 2020. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Bushby K, Finkel R, Birnkrant DJ. et al. DMD Care Considerations Working Group. Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and pharmacological and psychosocial management. Lancet Neurol 2010; 9 (01) 77-93
    CrossrefPubMedGoogle Scholar
  • 2 Ryder S, Leadley RM, Armstrong N. et al. The burden, epidemiology, costs and treatment for Duchenne muscular dystrophy: an evidence review. Orphanet J Rare Dis 2017; 12 (01) 79
    CrossrefPubMedGoogle Scholar
  • 3 Nigro G, Comi LI, Politano L, Bain RJ. The incidence and evolution of cardiomyopathy in Duchenne muscular dystrophy. Int J Cardiol 1990; 26 (03) 271-277
    CrossrefPubMedGoogle Scholar
  • 4 Maron BJ, Maron MS. Hypertrophic cardiomyopathy. Lancet 2013; 381 (9862): 242-255
    CrossrefPubMedGoogle Scholar
  • 5 Cirino AL, Seidman CE, Ho CY. Genetic testing and counseling for hypertrophic cardiomyopathy. Cardiol Clin 2019; 37 (01) 35-43
    CrossrefPubMedGoogle Scholar
  • 6 Sulem P, Helgason H, Oddson A. et al. Identification of a large set of rare complete human knockouts. Nat Genet 2015; 47 (05) 448-452
    CrossrefPubMedGoogle Scholar
  • 7 Chiu C, Bagnall RD, Ingles J. et al. Mutations in alpha-actinin-2 cause hypertrophic cardiomyopathy: a genome-wide analysis. J Am Coll Cardiol 2010; 55 (11) 1127-1135
    CrossrefPubMedGoogle Scholar
  • 8 Theis JL, Bos JM, Bartleson VB. et al. Echocardiographic-determined septal morphology in Z-disc hypertrophic cardiomyopathy. Biochem Biophys Res Commun 2006; 351 (04) 896-902
    CrossrefPubMedGoogle Scholar
  • 9 Nicol RL, Frey N, Pearson G, Cobb M, Richardson J, Olson EN. Activated MEK5 induces serial assembly of sarcomeres and eccentric cardiac hypertrophy. EMBO J 2001; 20 (11) 2757-2767
    CrossrefPubMedGoogle Scholar
  • 10 Kostareva A, Sejersen T, Sjoberg G. Genetic spectrum of cardiomyopathies with neuromuscular phenotype. Front Biosci (Schol Ed) 2013; 5: 325-340
    CrossrefPubMedGoogle Scholar
  • 11 Tandon A, Taylor MD, Cripe LH. Co-occurring Duchenne muscular dystrophy and hypertrophic cardiomyopathy in an adult with atypical cardiac phenotype. Cardiol Young 2015; 25 (02) 355-357
    CrossrefPubMedGoogle Scholar
  • 12 Beggs AH, Neumann PE, Arahata K. et al. Possible influences on the expression of X chromosome-linked dystrophin abnormalities by heterozygosity for autosomal recessive Fukuyama congenital muscular dystrophy. Proc Natl Acad Sci USA 1992; 89 (02) 623-627
    CrossrefPubMedGoogle Scholar
  • 13 Todorova A, Constantinova D, Kremensky I. Dilated cardiomyopathy and new 16 bp deletion in exon 44 of the dystrophin gene: the possible role of repeated motifs in mutation generation. Am J Med Genet A 2003; 120A (01) 5-7
    CrossrefPubMedGoogle Scholar
  • 14 Nigro G, Politano L, Nigro V, Petretta VR, Comi LI. Mutation of dystrophin gene and cardiomyopathy. Neuromuscul Disord 1994; 4 (04) 371-379
    CrossrefPubMedGoogle Scholar
  • 15 Gold R, Kress W, Meurers B, Meng G, Reichmann H, Müller CR. Becker muscular dystrophy: detection of unusual disease courses by combined approach to dystrophin analysis. Muscle Nerve 1992; 15 (02) 214-218
    CrossrefPubMedGoogle Scholar
  • 16 Beggs AH, Hoffman EP, Snyder JR. et al. Exploring the molecular basis for variability among patients with Becker muscular dystrophy: dystrophin gene and protein studies. Am J Hum Genet 1991; 49 (01) 54-67
    PubMedGoogle Scholar
  • 17 Muntoni F, Cau M, Ganau A. et al. Brief report: deletion of the dystrophin muscle-promoter region associated with X-linked dilated cardiomyopathy. N Engl J Med 1993; 329 (13) 921-925
    CrossrefPubMedGoogle Scholar
  • 18 Ribeiro Jr EdeA, Pinotsis N, Ghisleni A. et al. The structure and regulation of human muscle α-actinin. Cell 2014; 159 (06) 1447-1460
    CrossrefPubMedGoogle Scholar
  • 19 Hance JE, Fu SY, Watkins SC, Beggs AH, Michalak M. Alpha-actinin-2 is a new component of the dystrophin-glycoprotein complex. Arch Biochem Biophys 1999; 365 (02) 216-222
    CrossrefPubMedGoogle Scholar
  • 20 Gifford CA, Ranade SS, Samarakoon R. et al. Oligogenic inheritance of a human heart disease involving a genetic modifier. Science 2019; 364 (6443): 865-870
    CrossrefPubMedGoogle Scholar
  • 21 Kircher M, Witten DM, Jain P, O’Roak BJ, Cooper GM, Shendure J. A general framework for estimating the relative pathogenicity of human genetic variants. Nat Genet 2014; 46 (03) 310-315
    CrossrefPubMedGoogle Scholar