Congenital Muscular Dystrophy Treatment & Management

  • Author: Glenn Lopate, MD; Chief Editor: Amy Kao, MD   more...
 
Updated: Aug 17, 2011
 

Medical Care

  • No specific treatment is available for any of the congenital muscular dystrophies.
  • Aggressive supportive care is essential to preserve muscle activity, to allow for maximal functional ability, and to prolong the patient's life expectancy.
    • The primary neuromuscular concerns include prevention and correction of skeletal abnormalities, such as scoliosis, foot deformities, and contractures, to maintain ambulation.
    • Aggressive use of passive stretching, bracing, and orthopedic procedures, such as spinal fusion, allows the patient to remain independent for as long as possible.
  • Pulmonary complications are the other main concern.
    • Early monitoring and intervention to treat respiratory insufficiency is important because effective therapies can help to improve function and prolong life expectancy.
    • Such therapies include noninvasive bilevel positive airway pressure and/or continuous positive airway pressure or permanent ventilation via a tracheostomy.
  • Cardiac complications are especially common in patients with a mutation in FKRP and occasionally in patients with laminin-α2 deficiency. Treatment of dilated cardiomyopathy with ACE inhibitors and beta-blockers may be necessary.
  • Children with congenital muscular dystrophy may have other neurologic treatment issues, including seizure management, need for supplementary gastric tube feedings, ophthalmologic care, and general medical concerns that occur in profoundly retarded children.
  • As with other hereditary myopathies, a team approach, including a neurologist, pulmonologist, ophthalmologist, cardiologist, orthopedic surgeon, physical medicine specialist, orthotist, and counselors, is required to ensure the best possible care.
  • In patients with CMD with familial junctional epidermolysis bullosa besides the above standard measures, management must include supportive care to protect the skin from blistering, appropriate dressings, and prevention of secondary infections. Activities should minimize skin trauma.
Next

Surgical Care

Orthopedic surgery is often necessary in patients who live several years with their disease to prevent contractures and scoliosis.

Previous
Next

Consultations

  • Ophthalmologist
  • Pulmonologist
  • Cardiologist
  • Orthopedic surgeon
  • Epileptologist
  • Physical medicine specialist
  • Dermatologist (patients with CMD with familial junctional epidermolyis bullosa)
Previous
Proceed to Follow-up
 
 
Contributor Information and Disclosures
Author

Glenn Lopate, MD  Associate Professor, Department of Neurology, Division of Neuromuscular Diseases, Washington University School of Medicine; Director of Neurology Clinic, St Louis ConnectCare; Consulting Staff, Department of Neurology, Barnes-Jewish Hospital

Glenn Lopate, MD is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, and Phi Beta Kappa

Disclosure: Baxter Grant/research funds Other; Amgen Grant/research funds None

Specialty Editor Board

Robert Stanley Rust Jr, MD, MA  Thomas E Worrell Jr Professor of Epileptology and Neurology, Co-Director of FE Dreifuss Child Neurology and Epilepsy Clinics, Director, Child Neurology, University of Virginia School of Medicine; Chair-Elect, Child Neurology Section, American Academy of Neurology

Robert Stanley Rust Jr, MD, MA is a member of the following medical societies: American Academy of Neurology, American Epilepsy Society, American Headache Society, American Neurological Association, Child Neurology Society, International Child Neurology Association, and Society for Pediatric Research

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Kenneth J Mack, MD, PhD  Senior Associate Consultant, Department of Child and Adolescent Neurology, Mayo Clinic

Kenneth J Mack, MD, PhD is a member of the following medical societies: American Academy of Neurology, Child Neurology Society, Phi Beta Kappa, and Society for Neuroscience

Disclosure: Nothing to disclose.

Chief Editor

Amy Kao, MD  Attending Neurologist, Children's National Medical Center

Amy Kao, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Pediatrics, American Epilepsy Society, and Child Neurology Society

Disclosure: Nothing to disclose.

References

  1. Fukuyama Y, Kwazura M, Haruna H. A peculiar form of congenital muscular dystrophy. Paediatr Univ Tokyo. 1960;4:5-8.

  2. Sparks SE, Escolar DM. Congenital muscular dystrophies. Handb Clin Neurol. 2011;101:47-79. [Medline].

  3. Geranmayeh F, Clement E, Feng LH, et al. Genotype-phenotype correlation in a large population of muscular dystrophy patients with LAMA2 mutations. Neuromuscul Disord. Apr 2010;20(4):241-50. [Medline].

  4. Bonnemann CG. The collagen VI-related myopathies: muscle meets its matrix. Nat Rev Neurol. Jun 21 2011;7(7):379-90. [Medline].

  5. Scacheri PC, Gillanders EM, Subramony SH, et al. Novel mutations in collagen VI genes: expansion of the Bethlem myopathy phenotype. Neurology. Feb 26 2002;58(4):593-602. [Medline].

  6. Merlini L, Martoni E, Grumati P, et al. Autosomal recessive myosclerosis myopathy is a collagen VI disorder. Neurology. Oct 14 2008;71(16):1245-53. [Medline].

  7. Nakashima H, Kibe T, Yokochi K. 'Congenital muscular dystrophy caused by integrin alpha7 deficiency'. Dev Med Child Neurol. Mar 2009;51(3):245. [Medline].

  8. Forrest K, Mellerio JE, Robb S, et al. Congenital muscular dystrophy, myasthenic symptoms and epidermolysis bullosa simplex (EBS) associated with mutations in the PLEC1 gene encoding plectin. Neuromuscul Disord. Nov 2010;20(11):709-11. [Medline].

  9. Yiu EM, Klausegger A, Waddell LB, et al. Epidermolysis bullosa with late-onset muscular dystrophy and plectin deficiency. Muscle Nerve. Jul 2011;44(1):135-41. [Medline].

  10. Gundesli H, Talim B, Korkusuz P, et al. Mutation in exon 1f of PLEC, leading to disruption of plectin isoform 1f, causes autosomal-recessive limb-girdle muscular dystrophy. Am J Hum Genet. Dec 10 2010;87(6):834-41. [Medline].

  11. Schara U, Kress W, Bonnemann CG, Breitbach-Faller N, Korenke CG, Schreiber G, et al. The phenotype and long-term follow-up in 11 patients with juvenile selenoprotein N1-related myopathy. Eur J Paediatr Neurol. May 2008;12(3):224-30. [Medline].

  12. Akiyama T, Ohtsuka Y, Takata T, Hattori J, Kawakita Y, Saito K. The mildest known case of Fukuyama-type congenital muscular dystrophy. Brain Dev. Sep 2006;28(8):537-40. [Medline].

  13. Godfrey C, Escolar D, Brockington M, Clement EM, Mein R, Jimenez-Mallebrera C, et al. Fukutin gene mutations in steroid-responsive limb girdle muscular dystrophy. Ann Neurol. Nov 2006;60(5):603-10. [Medline].

  14. Murakami T, Hayashi YK, Noguchi S, Ogawa M, Nonaka I, Tanabe Y. Fukutin gene mutations cause dilated cardiomyopathy with minimal muscle weakness. Ann Neurol. Nov 2006;60(5):597-602. [Medline].

  15. Godfrey C, Clement E, Mein R, Brockington M, Smith J, Talim B. Refining genotype phenotype correlations in muscular dystrophies with defective glycosylation of dystroglycan. Brain. Oct 2007;130(Pt 10):2725-35. [Medline].

  16. Messina S, Tortorella G, Concolino D, et al. Congenital muscular dystrophy with defective alpha-dystroglycan, cerebellar hypoplasia, and epilepsy. Neurology. Nov 10 2009;73(19):1599-601. [Medline].

  17. Balci B, Uyanik G, Dincer P, Gross C, Willer T, Talim B. An autosomal recessive limb girdle muscular dystrophy (LGMD2) with mild mental retardation is allelic to Walker-Warburg syndrome (WWS) caused by a mutation in the POMT1 gene. Neuromuscul Disord. Apr 2005;15(4):271-5. [Medline].

  18. Biancheri R, Falace A, Tessa A, et al. POMT2 gene mutation in limb-girdle muscular dystrophy with inflammatory changes. Biochem Biophys Res Commun. Nov 30 2007;363(4):1033-7. [Medline].

  19. Mercuri E, Messina S, Bruno C, et al. Congenital muscular dystrophies with defective glycosylation of dystroglycan: a population study. Neurology. May 26 2009;72(21):1802-9. [Medline].

  20. Clarke NF, Maugenre S, Vandebrouck A, et al. Congenital muscular dystrophy type 1D (MDC1D) due to a large intragenic insertion/deletion, involving intron 10 of the LARGE gene. Eur J Hum Genet. Apr 2011;19(4):452-7. [Medline].

  21. van Reeuwijk J, Grewal PK, Salih MA, Beltran-Valero de Bernabe D, McLaughlan JM, Michielse CB, et al. Intragenic deletion in the LARGE gene causes Walker-Warburg syndrome. Hum Genet. Jul 2007;121(6):685-90. [Medline].

  22. Zou Y, Zhang RZ, Sabatelli P, Chu ML, Bönnemann CG. Muscle interstitial fibroblasts are the main source of collagen VI synthesis in skeletal muscle: implications for congenital muscular dystrophy types Ullrich and Bethlem. J Neuropathol Exp Neurol. Feb 2008;67(2):144-54. [Medline].

  23. Brinas L, Richard P, Quijano-Roy S, et al. Early onset collagen VI myopathies: Genetic and clinical correlations. Ann Neurol. Oct 2010;68(4):511-20. [Medline].

  24. Lampe AK, Zou Y, Sudano D, O'Brien KK, Hicks D, Laval SH, et al. Exon skipping mutations in collagen VI are common and are predictive for severity and inheritance. Hum Mutat. Jun 2008;29(6):809-22. [Medline].

  25. Chavanas S, Pulkkinen L, Gache Y, et al. A homozygous nonsense mutation in the PLEC1 gene in patients with epidermolysis bullosa simplex with muscular dystrophy. J Clin Invest. Nov 15 1996;98(10):2196-200. [Medline]. [Full Text].

  26. Pulkkinen L, Smith FJ, Shimizu H, et al. Homozygous deletion mutations in the plectin gene (PLEC1) in patients with epidermolysis bullosa simplex associated with late-onset muscular dystrophy. Hum Mol Genet. Oct 1996;5(10):1539-46. [Medline].

  27. Rezniczek GA, Walko G, Wiche G. Plectin gene defects lead to various forms of epidermolysis bullosa simplex. Dermatol Clin. Jan 2010;28(1):33-41. [Medline].

  28. Schoenmakers E, Agostini M, Mitchell C, et al. Mutations in the selenocysteine insertion sequence-binding protein 2 gene lead to a multisystem selenoprotein deficiency disorder in humans. J Clin Invest. Dec 1 2010;120(12):4220-35. [Medline]. [Full Text].

  29. Jimenez-Mallebrera C, Torelli S, Feng L, et al. A comparative study of alpha-dystroglycan glycosylation in dystroglycanopathies suggests that the hypoglycosylation of alpha-dystroglycan does not consistently correlate with clinical severity. Brain Pathol. Oct 2009;19(4):596-611. [Medline]. [Full Text].

  30. Clement EM, Godfrey C, Tan J, et al. Mild POMGnT1 mutations underlie a novel limb-girdle muscular dystrophy variant. Arch Neurol. Jan 2008;65(1):137-41. [Medline].

  31. Keramaris-Vrantsis E, Lu PJ, Doran T, Zillmer A, Ashar J, Esapa CT. Fukutin-related protein localizes to the Golgi apparatus and mutations lead to mislocalization in muscle in vivo. Muscle Nerve. Oct 2007;36(4):455-65. [Medline].

  32. Mercuri E, Clements E, Offiah A, et al. Muscle magnetic resonance imaging involvement in muscular dystrophies with rigidity of the spine. Ann Neurol. Feb 2010;67(2):201-8. [Medline].

  33. Baker NL, Morgelin M, Peat R, et al. Dominant collagen VI mutations are a common cause of Ullrich congenital muscular dystrophy. Hum Mol Genet. Jan 15 2005;14(2):279-93. [Medline].

  34. Barresi R, Michele DE, Kanagawa M. LARGE can functionally bypass alpha-dystroglycan glycosylation defects in distinct congenital muscular dystrophies. Nat Med. Jul 2004;10(7):696-703. [Medline].

  35. Batten FE. Three cases of myopathy, infantile type. Brain. 1903;26:147-8.

  36. Beltran-Valero de Bernabe D, Currier S, Steinbrecher A, et al. Mutations in the O-mannosyltransferase gene POMT1 give rise to the severe neuronal migration disorder Walker-Warburg syndrome. Am J Hum Genet. Nov 2002;71(5):1033-43. [Medline].

  37. Brockington M, Torelli S, Prandini P, et al. Localization and functional analysis of the LARGE family of glycosyltransferases: significance for muscular dystrophy. Hum Mol Genet. Mar 1 2005;14(5):657-65. [Medline].

  38. Camacho Vanegas O, Bertini E, Zhang RZ, et al. Ullrich scleroatonic muscular dystrophy is caused by recessive mutations in collagen type VI. Proc Natl Acad Sci U S A. Jun 19 2001;98(13):7516-21. [Medline].

  39. Center for Human and Clinical Genetics. Leiden University Medical Center. Leiden Muscular Dystrophy Pages: Duchenne and Duchenne-like muscular dystrophies. Available at: http://www.dmd.nl. [Full Text].

  40. Cohn RD. Dystroglycan: important player in skeletal muscle and beyond. Neuromuscul Disord. Mar 2005;15(3):207-17. [Medline].

  41. Currier SC, Lee CK, Chang BS, et al. Mutations in POMT1 are found in a minority of patients with Walker-Warburg syndrome. Am J Med Genet A. Feb 15 2005;133(1):53-7. [Medline].

  42. DAmico A, Haliloglu G, Richard P, et al. Two patients with Dropped head syndrome due to mutations in LMNA or SEPN1 genes. Neuromuscul Disord. Aug 2005;15(8):521-4. [Medline].

  43. DAmico A, Tessa A, Bruno C, et al. Expanding the clinical spectrum of POMT1 phenotype. Neurology. May 23 2006;66(10):1564-7; discussion 1461. [Medline].

  44. Di Blasi C, Piga D, Brioschi P, et al. LAMA2 gene analysis in congenital muscular dystrophy: new mutations, prenatal diagnosis, and founder effect. Arch Neurol. Oct 2005;62(10):1582-6. [Medline].

  45. Dubowitz V. Rigid spine syndrome: a muscle syndrome in search of a name. Proc R Soc Med. Mar 1973;66(3):219-20. [Medline].

  46. Esapa CT, McIlhinney RA, Blake DJ. Fukutin-related protein mutations that cause congenital muscular dystrophy result in ER-retention of the mutant protein in cultured cells. Hum Mol Genet. Jan 15 2005;14(2):295-305. [Medline].

  47. Giusti B, Lucarini L, Pietroni V, et al. Dominant and recessive COL6A1 mutations in Ullrich scleroatonic muscular dystrophy. Ann Neurol. Sep 2005;58(3):400-10. [Medline].

  48. Grewal PK, Holzfeind PJ, Bittner RE, Hewitt JE. Mutant glycosyltransferase and altered glycosylation of alpha-dystroglycan in the myodystrophy mouse. Nat Genet. Jun 2001;28(2):151-4. [Medline].

  49. Grewal PK, McLaughlan JM, Moore CJ, et al. Characterization of the LARGE family of putative glycosyltransferases associated with dystroglycanopathies. Glycobiology. Oct 2005;15(10):912-23. [Medline].

  50. Guglieri M, Magri F, Comi GP. Molecular etiopathogenesis of limb girdle muscular and congenital muscular dystrophies: boundaries and contiguities. Clin Chim Acta. Nov 2005;361(1-2):54-79. [Medline].

  51. Haliloglu G, Gross C, Senbil N. Clinical spectrum of muscle-eyebraindisease: From the typical presentation to severe autistic features. Acta Myol. 2004;23:137-139.

  52. Hayashi YK, Chou FL, Engvall E, et al. Mutations in the integrin alpha7 gene cause congenital myopathy. Nat Genet. May 1998;19(1):94-7. [Medline].

  53. Helbling-Leclerc A, Zhang X, Topaloglu H, et al. Mutations in the laminin alpha 2-chain gene (LAMA2) cause merosin-deficient congenital muscular dystrophy. Nat Genet. Oct 1995;11(2):216-8. [Medline].

  54. Henion TR, Qu Q, Smith FI. Expression of dystroglycan, fukutin and POMGnT1 during mouse cerebellar development. Brain Res Mol Brain Res. Apr 10 2003;112(1-2):177-81. [Medline].

  55. Howard RA. A case of congenital defect of the muscular system (dystrophia muscularis congenita) and its association with congenital talipes equino-varus. Proc R Soc Med. 1908;1:157-66.

  56. Jimenez-Mallebrera C, Brown SC, Sewry CA, et al. Congenital muscular dystrophy: molecular and cellular aspects. Cell Mol Life Sci. Apr 2005;62(7-8):809-23. [Medline].

  57. Kobayashi K, Nakahori Y, Miyake M, et al. An ancient retrotransposal insertion causes Fukuyama-type congenital muscular dystrophy. Nature. Jul 23 1998;394(6691):388-92. [Medline].

  58. Lampe AK, Bushby KM. Collagen VI related muscle disorders. J Med Genet. Sep 2005;42(9):673-85. [Medline].

  59. Liu J, Ball SL, Yang Y, et al. A genetic model for muscle-eye-brain disease in mice lacking protein O-mannose 1,2-N-acetylglucosaminyltransferase (POMGnT1). Mech Dev. Mar 2006;123(3):228-40. [Medline].

  60. Longman C, Brockington M, Torelli S, et al. Mutations in the human LARGE gene cause MDC1D, a novel form of congenital muscular dystrophy with severe mental retardation and abnormal glycosylation of alpha-dystroglycan. Hum Mol Genet. Nov 1 2003;12(21):2853-61. [Medline].

  61. Martin PT. The dystroglycanopathies: the new disorders of O-linked glycosylation. Semin Pediatr Neurol. Sep 2005;12(3):152-8. [Medline].

  62. Matsumoto H, Hayashi YK, Kim DS, et al. Congenital muscular dystrophy with glycosylation defects of alpha-dystroglycan in Japan. Neuromuscul Disord. May 2005;15(5):342-8. [Medline].

  63. Mayer U, Saher G, Fassler R, et al. Absence of integrin alpha 7 causes a novel form of muscular dystrophy. Nat Genet. Nov 1997;17(3):318-23. [Medline].

  64. Mercuri E, Topaloglu H, Brockington M, et al. Spectrum of brain changes in patients with congenital muscular dystrophy and FKRP gene mutations. Arch Neurol. Feb 2006;63(2):251-7. [Medline].

  65. Moghadaszadeh B, Petit N, Jaillard C, et al. Mutations in SEPN1 cause congenital muscular dystrophy with spinal rigidity and restrictive respiratory syndrome. Nat Genet. Sep 2001;29(1):17-8. [Medline].

  66. Moore SA, Saito F, Chen J, et al. Deletion of brain dystroglycan recapitulates aspects of congenital muscular dystrophy. Nature. Jul 25 2002;418(6896):422-5. [Medline].

  67. Pestronk A. Washington University Neuromuscular Disease Center Web page. 1999. Available at: http://www.neuro.wustl.edu/neuromuscular. [Full Text].

  68. Raitta C, Lamminen M, Santavuori P, Leisti J. Ophthalmological findings in a new syndrome with muscle, eye and brain involvement. Acta Ophthalmol (Copenh). Jun 1978;56(3):465-72. [Medline].

  69. Rederstorff M, Krol A, Lescure A, et al. Understanding the importance of selenium and selenoproteins in muscle function. Cell Mol Life Sci. Jan 2006;63(1):52-9. [Medline].

  70. Santavuori P, Leisti J, Kruus S. Muscle-eye-brain disease: a new syndrome. Neuropadiatrie. 1977;8(suppl):550.

  71. Taniguchi K, Kobayashi K, Saito K, et al. Worldwide distribution and broader clinical spectrum of muscle-eye-brain disease. Hum Mol Genet. Mar 1 2003;12(5):527-34. [Medline].

  72. Tome FM, Evangelista T, Leclerc A, et al. Congenital muscular dystrophy with merosin deficiency. C R Acad Sci III. Apr 1994;317(4):351-7. [Medline].

  73. Tsao CY, Mendell JR. The childhood muscular dystrophies: making order out of chaos. Semin Neurol. 1999;19(1):9-23. [Medline].

  74. Vainzof M, Richard P, Herrmann R, et al. Prenatal diagnosis in laminin alpha2 chain (merosin)-deficient congenital muscular dystrophy: a collective experience of five international centers. Neuromuscul Disord. Oct 2005;15(9-10):588-94. [Medline].

  75. van Reeuwijk J, Janssen M, van den Elzen C, et al. POMT2 mutations cause alpha-dystroglycan hypoglycosylation and Walker-Warburg syndrome. J Med Genet. Dec 2005;42(12):907-12. [Medline].

  76. van Reeuwijk J, Maugenre S, van den Elzen C, et al. The expanding phenotype of POMT1 mutations: from Walker-Warburg syndrome to congenital muscular dystrophy, microcephaly, and mental retardation. Hum Mutat. May 2006;27(5):453-9. [Medline].

  77. Voit T, Tome FS. The congenital muscular dystrophies. In: Engel AG, Franzini-Armstrong C, eds. Myology. New York: McGraw-Hill. 2004: 1203-38.

  78. Walker AE. Lissencephaly. Arch Neurol Psychiat. 1942;48:13-29.

  79. Warburg M. Heterogeneity of congenital retinal non-attachment, falciform folds and retinal dysplasia. A guide to genetic counselling. Hum Hered. 1976;26(2):137-48. [Medline].

  80. Willer T, Prados B, Falcon-Perez JM, et al. Targeted disruption of the Walker-Warburg syndrome gene Pomt1 in mouse results in embryonic lethality. Proc Natl Acad Sci U S A. Sep 28 2004;101(39):14126-31. [Medline].

  81. Yoshida A, Kobayashi K, Manya H, et al. Muscular dystrophy and neuronal migration disorder caused by mutations in a glycosyltransferase, POMGnT1. Dev Cell. Nov 2001;1(5):717-24. [Medline].

 
Previous
Next
 
Dystrophin-glycoprotein complex. The complex bridges the inner cytoskeleton (F-actin) and the basal lamina. Mutations in laminin-α2, integrin α7, and O-glycosyltransferases that glycosylate alpha-dystroglycan all can cause congenital muscular dystrophy (CMD). Furthermore, mutations in collagen (not shown), which binds alpha-dystroglycan through perlecan and other proteoglycans, can cause CMD. Mutations in dystrophin, the sarcoglycans, dysferlin, and caveolin-3 can also cause muscular dystrophies. Reprinted with permission from Cohn RD. Dystroglycan: important player in skeletal muscle and beyond. In: Neuromuscular Disorders. Vol. 15. Cohn RD. Elsevier; 2005: 207-17. 7, 20
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2012 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.