Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Oculopharyngeal, distal, and congenital muscular dystrophies

Basil T Darras, MD
Section Editors
Douglas R Nordli, Jr, MD
Jeremy M Shefner, MD, PhD
Deputy Editor
John F Dashe, MD, PhD


The muscular dystrophies are an inherited group of progressive myopathic disorders resulting from defects in a number of genes required for normal muscle function. Some of the genes responsible for these conditions have been identified. Muscle weakness is the primary symptom.

The pathogenesis, genetics, and clinical characteristics of oculopharyngeal, distal, and congenital muscular dystrophies are discussed here. Other muscular dystrophies are presented separately. (See "Clinical features and diagnosis of Duchenne and Becker muscular dystrophy" and "Emery-Dreifuss muscular dystrophy" and "Facioscapulohumeral muscular dystrophy" and "Limb-girdle muscular dystrophy" and "Myotonic dystrophy: Etiology, clinical features, and diagnosis".)


Oculopharyngeal muscular dystrophy (OPMD) is a rare myopathy that is characterized by ocular and pharyngeal muscle involvement, leading to ptosis and dysphagia [1,2].

Clinical features — OPMD typically presents with ptosis, dysarthria, and dysphagia. It can also be associated with proximal and distal extremity weakness. The onset is usually in middle age with asymmetric involvement of the levator palpebrae muscles. Progressive extraocular weakness subsequently develops. In general, OPMD is a slowly progressive myopathy. However, ptosis can occlude vision, and severe dysphagia may lead to weight loss and death if not treated.

Differential diagnosis — OPMD is distinguished from facioscapulohumeral dystrophy (FSHD) by the different distributions of weakness. Extraocular weakness is far more severe in OPMD. (See "Facioscapulohumeral muscular dystrophy".)

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:

Subscribers log in here

Literature review current through: Nov 2017. | This topic last updated: Jun 08, 2017.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. VICTOR M, HAYES R, ADAMS RD. Oculopharyngeal muscular dystrophy. A familial disease of late life characterized by dysphagia and progressive ptosis of the evelids. N Engl J Med 1962; 267:1267.
  2. Trollet C, Gidaro T, Klein P, et al. Oculopharyngeal muscular dystrophy. GeneReviews. https://www.ncbi.nlm.nih.gov/books/NBK1126/ (Accessed on May 03, 2017).
  3. Barbeau A. The symptom of hereditary late-onset ptosis and dysphagia in French-Canada. In: Symposium uber progressive muskeldystrophie, Kuhn E (Ed), Springer-Verlag, Berlin 1966. p.102.
  4. Blumen SC, Nisipeanu P, Sadeh M, et al. Epidemiology and inheritance of oculopharyngeal muscular dystrophy in Israel. Neuromuscul Disord 1997; 7 Suppl 1:S38.
  5. Blumen SC, Korczyn AD, Lavoie H, et al. Oculopharyngeal MD among Bukhara Jews is due to a founder (GCG)9 mutation in the PABP2 gene. Neurology 2000; 55:1267.
  6. Grewal RP, Karkera JD, Grewal RK, Detera-Wadleigh SD. Mutation analysis of oculopharyngeal muscular dystrophy in Hispanic American families. Arch Neurol 1999; 56:1378.
  7. Becher MW, Morrison L, Davis LE, et al. Oculopharyngeal muscular dystrophy in Hispanic New Mexicans. JAMA 2001; 286:2437.
  8. Brais B. Oculopharyngeal muscular dystrophy: a polyalanine myopathy. Curr Neurol Neurosci Rep 2009; 9:76.
  9. Raz V, Butler-Browne G, van Engelen B, Brais B. 191st ENMC international workshop: recent advances in oculopharyngeal muscular dystrophy research: from bench to bedside 8-10 June 2012, Naarden, The Netherlands. Neuromuscul Disord 2013; 23:516.
  10. Brais B, Bouchard JP, Xie YG, et al. Short GCG expansions in the PABP2 gene cause oculopharyngeal muscular dystrophy. Nat Genet 1998; 18:164.
  11. Hebbar S, Webberley MJ, Lunt P, Robinson DO. Siblings with recessive oculopharyngeal muscular dystrophy. Neuromuscul Disord 2007; 17:254.
  12. Richard P, Trollet C, Gidaro T, et al. PABPN1 (GCN)11 as a Dominant Allele in Oculopharyngeal Muscular Dystrophy -Consequences in Clinical Diagnosis and Genetic Counselling. J Neuromuscul Dis 2015; 2:175.
  13. Calado A, Tomé FM, Brais B, et al. Nuclear inclusions in oculopharyngeal muscular dystrophy consist of poly(A) binding protein 2 aggregates which sequester poly(A) RNA. Hum Mol Genet 2000; 9:2321.
  14. Richard P, Trollet C, Stojkovic T, et al. Correlation between PABPN1 genotype and disease severity in oculopharyngeal muscular dystrophy. Neurology 2017; 88:359.
  15. Blumen SC, Brais B, Korczyn AD, et al. Homozygotes for oculopharyngeal muscular dystrophy have a severe form of the disease. Ann Neurol 1999; 46:115.
  16. Blumen SC, Bouchard JP, Brais B, et al. Cognitive impairment and reduced life span of oculopharyngeal muscular dystrophy homozygotes. Neurology 2009; 73:596.
  17. Duranceau A. Cricopharyngeal myotomy in the management of neurogenic and muscular dysphagia. Neuromuscul Disord 1997; 7 Suppl 1:S85.
  18. Davies JE, Wang L, Garcia-Oroz L, et al. Doxycycline attenuates and delays toxicity of the oculopharyngeal muscular dystrophy mutation in transgenic mice. Nat Med 2005; 11:672.
  19. Davies JE, Rose C, Sarkar S, Rubinsztein DC. Cystamine suppresses polyalanine toxicity in a mouse model of oculopharyngeal muscular dystrophy. Sci Transl Med 2010; 2:34ra40.
  20. Orrell RW, Darras BT, Griggs RC. Facioscapulohumeral dystrophy, scapuloperoneal syndromes, and distal myopathies. In: Neuromuscular disorders in infancy, childhood, and adolescence: A clinician's approach, Jones HR, De Vivo DC, Darras BT (Eds), Butterworth Heinemann, Philadelphia 2003. p.701.
  21. Suominen T, Udd B, Hackman P. Udd distal myopathy. GeneReviews. www.ncbi.nlm.nih.gov/books/NBK1323/ (Accessed on January 18, 2011).
  22. Guergueltcheva V, Peeters K, Baets J, et al. Distal myopathy with upper limb predominance caused by filamin C haploinsufficiency. Neurology 2011; 77:2105.
  23. Schessl J, Kress W, Schoser B. Novel ANO5 mutations causing hyper-CK-emia, limb girdle muscular weakness and Miyoshi type of muscular dystrophy. Muscle Nerve 2012; 45:740.
  24. Bolduc V, Marlow G, Boycott KM, et al. Recessive mutations in the putative calcium-activated chloride channel Anoctamin 5 cause proximal LGMD2L and distal MMD3 muscular dystrophies. Am J Hum Genet 2010; 86:213.
  25. Hackman P, Sarparanta J, Lehtinen S, et al. Welander distal myopathy is caused by a mutation in the RNA-binding protein TIA1. Ann Neurol 2013; 73:500.
  26. Müller TJ, Kraya T, Stoltenburg-Didinger G, et al. Phenotype of matrin-3-related distal myopathy in 16 German patients. Ann Neurol 2014; 76:669.
  27. Johnson JO, Pioro EP, Boehringer A, et al. Mutations in the Matrin 3 gene cause familial amyotrophic lateral sclerosis. Nat Neurosci 2014; 17:664.
  28. Bucelli RC, Arhzaouy K, Pestronk A, et al. SQSTM1 splice site mutation in distal myopathy with rimmed vacuoles. Neurology 2015; 85:665.
  29. Kang PB, Morrison L, Iannaccone ST, et al. Evidence-based guideline summary: evaluation, diagnosis, and management of congenital muscular dystrophy: Report of the Guideline Development Subcommittee of the American Academy of Neurology and the Practice Issues Review Panel of the American Association of Neuromuscular & Electrodiagnostic Medicine. Neurology 2015; 84:1369.
  30. Sparks S, Quijano-Roy S, Harper A, et al. Congenital muscular dystrophy overview. GeneReviews. www.ncbi.nlm.nih.gov/books/NBK1291/ (Accessed on September 05, 2012).
  31. Mercuri E, Muntoni F. The ever-expanding spectrum of congenital muscular dystrophies. Ann Neurol 2012; 72:9.
  32. Bönnemann CG, Wang CH, Quijano-Roy S, et al. Diagnostic approach to the congenital muscular dystrophies. Neuromuscul Disord 2014; 24:289.
  33. Pini A, Merlini L, Tomé FM, et al. Merosin-negative congenital muscular dystrophy, occipital epilepsy with periodic spasms and focal cortical dysplasia. Report of three Italian cases in two families. Brain Dev 1996; 18:316.
  34. Messina S, Bruno C, Moroni I, et al. Congenital muscular dystrophies with cognitive impairment. A population study. Neurology 2010; 75:898.
  35. Gordon E, Hoffman EP, Pegoraro E. Congenital muscular dystrophy overview. www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=cmd-overview (Accessed on September 20, 2010).
  36. Finsterer J, Ramaciotti C, Wang CH, et al. Cardiac findings in congenital muscular dystrophies. Pediatrics 2010; 126:538.
  37. 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 1995; 11:216.
  38. Nadeau A, Kinali M, Main M, et al. Natural history of Ullrich congenital muscular dystrophy. Neurology 2009; 73:25.
  39. 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 2001; 98:7516.
  40. Demir E, Sabatelli P, Allamand V, et al. Mutations in COL6A3 cause severe and mild phenotypes of Ullrich congenital muscular dystrophy. Am J Hum Genet 2002; 70:1446.
  41. Pan TC, Zhang RZ, Sudano DG, et al. New molecular mechanism for Ullrich congenital muscular dystrophy: a heterozygous in-frame deletion in the COL6A1 gene causes a severe phenotype. Am J Hum Genet 2003; 73:355.
  42. Baker NL, Mörgelin M, Peat R, et al. Dominant collagen VI mutations are a common cause of Ullrich congenital muscular dystrophy. Hum Mol Genet 2005; 14:279.
  43. Giusti B, Lucarini L, Pietroni V, et al. Dominant and recessive COL6A1 mutations in Ullrich scleroatonic muscular dystrophy. Ann Neurol 2005; 58:400.
  44. Lampe AK, Bushby KM. Collagen VI related muscle disorders. J Med Genet 2005; 42:673.
  45. Bethlem J, Wijngaarden GK. Benign myopathy, with autosomal dominant inheritance. A report on three pedigrees. Brain 1976; 99:91.
  46. Baker NL, Mörgelin M, Pace RA, et al. Molecular consequences of dominant Bethlem myopathy collagen VI mutations. Ann Neurol 2007; 62:390.
  47. Deconinck N, Richard P, Allamand V, et al. Bethlem myopathy: long-term follow-up identifies COL6 mutations predicting severe clinical evolution. J Neurol Neurosurg Psychiatry 2015; 86:1337.
  48. Gualandi F, Urciuolo A, Martoni E, et al. Autosomal recessive Bethlem myopathy. Neurology 2009; 73:1883.
  49. Briñas L, Richard P, Quijano-Roy S, et al. Early onset collagen VI myopathies: Genetic and clinical correlations. Ann Neurol 2010; 68:511.
  50. Brun BN, Mockler SR, Laubscher KM, et al. Comparison of brain MRI findings with language and motor function in the dystroglycanopathies. Neurology 2017; 88:623.
  51. Mercuri E, Messina S, Bruno C, et al. Congenital muscular dystrophies with defective glycosylation of dystroglycan: a population study. Neurology 2009; 72:1802.
  52. Yanagisawa A, Bouchet C, Van den Bergh PY, et al. New POMT2 mutations causing congenital muscular dystrophy: identification of a founder mutation. Neurology 2007; 69:1254.
  53. Godfrey C, Clement E, Mein R, et al. Refining genotype phenotype correlations in muscular dystrophies with defective glycosylation of dystroglycan. Brain 2007; 130:2725.
  54. Clement E, Mercuri E, Godfrey C, et al. Brain involvement in muscular dystrophies with defective dystroglycan glycosylation. Ann Neurol 2008; 64:573.
  55. Villanova M, Mercuri E, Bertini E, et al. Congenital muscular dystrophy associated with calf hypertrophy, microcephaly and severe mental retardation in three Italian families: evidence for a novel CMD syndrome. Neuromuscul Disord 2000; 10:541.
  56. Brockington M, Blake DJ, Prandini P, et al. Mutations in the fukutin-related protein gene (FKRP) cause a form of congenital muscular dystrophy with secondary laminin alpha2 deficiency and abnormal glycosylation of alpha-dystroglycan. Am J Hum Genet 2001; 69:1198.
  57. Mercuri E, Topaloglu H, Brockington M, et al. Spectrum of brain changes in patients with congenital muscular dystrophy and FKRP gene mutations. Arch Neurol 2006; 63:251.
  58. 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 2003; 12:2853.
  59. Kobayashi K, Nakahori Y, Miyake M, et al. An ancient retrotransposal insertion causes Fukuyama-type congenital muscular dystrophy. Nature 1998; 394:388.
  60. Kamoshita S, Konishi Y, Segawa M, Fukuyama Y. Congenital muscular dystrophy as a disease of the central nervous system. Arch Neurol 1976; 33:513.
  61. Toda T, Kobayashi K, Kondo-Iida E, et al. The Fukuyama congenital muscular dystrophy story. Neuromuscul Disord 2000; 10:153.
  62. Toda T, Segawa M, Nomura Y, et al. Localization of a gene for Fukuyama type congenital muscular dystrophy to chromosome 9q31-33. Nat Genet 1993; 5:283.
  63. Yamamoto T, Shibata N, Kanazawa M, et al. Early ultrastructural changes in the central nervous system in Fukuyama congenital muscular dystrophy. Ultrastruct Pathol 1997; 21:355.
  64. Murakami T, Hayashi YK, Noguchi S, et al. Fukutin gene mutations cause dilated cardiomyopathy with minimal muscle weakness. Ann Neurol 2006; 60:597.
  65. Dobyns WB, Pagon RA, Armstrong D, et al. Diagnostic criteria for Walker-Warburg syndrome. Am J Med Genet 1989; 32:195.
  66. Beltrán-Valero de Bernabé 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 2002; 71:1033.
  67. van Reeuwijk J, Janssen M, van den Elzen C, et al. POMT2 mutations cause alpha-dystroglycan hypoglycosylation and Walker-Warburg syndrome. J Med Genet 2005; 42:907.
  68. van Reeuwijk J, Brunner HG, van Bokhoven H. Glyc-O-genetics of Walker-Warburg syndrome. Clin Genet 2005; 67:281.
  69. de Bernabé DB, van Bokhoven H, van Beusekom E, et al. A homozygous nonsense mutation in the fukutin gene causes a Walker-Warburg syndrome phenotype. J Med Genet 2003; 40:845.
  70. Silan F, Yoshioka M, Kobayashi K, et al. A new mutation of the fukutin gene in a non-Japanese patient. Ann Neurol 2003; 53:392.
  71. Beltran-Valero de Bernabé D, Voit T, Longman C, et al. Mutations in the FKRP gene can cause muscle-eye-brain disease and Walker-Warburg syndrome. J Med Genet 2004; 41:e61.
  72. Clement EM, Godfrey C, Tan J, et al. Mild POMGnT1 mutations underlie a novel limb-girdle muscular dystrophy variant. Arch Neurol 2008; 65:137.
  73. van Reeuwijk J, Grewal PK, Salih MA, et al. Intragenic deletion in the LARGE gene causes Walker-Warburg syndrome. Hum Genet 2007; 121:685.
  74. Willer T, Lee H, Lommel M, et al. ISPD loss-of-function mutations disrupt dystroglycan O-mannosylation and cause Walker-Warburg syndrome. Nat Genet 2012; 44:575.
  75. Roscioli T, Kamsteeg EJ, Buysse K, et al. Mutations in ISPD cause Walker-Warburg syndrome and defective glycosylation of α-dystroglycan. Nat Genet 2012; 44:581.
  76. Manzini MC, Tambunan DE, Hill RS, et al. Exome sequencing and functional validation in zebrafish identify GTDC2 mutations as a cause of Walker-Warburg syndrome. Am J Hum Genet 2012; 91:541.
  77. Riemersma M, Mandel H, van Beusekom E, et al. Absence of α- and β-dystroglycan is associated with Walker-Warburg syndrome. Neurology 2015; 84:2177.
  78. D'Amico A, Tessa A, Bruno C, et al. Expanding the clinical spectrum of POMT1 phenotype. Neurology 2006; 66:1564.
  79. Santavuori P, Somer H, Sainio K, et al. Muscle-eye-brain disease (MEB). Brain Dev 1989; 11:147.
  80. Jones K, North K. The congenital muscular dystrophies. In: Neuromuscular Disorders of Infancy, Childhood, and Adolescence: A Clinician's Approach, Jones HR, De Vivo DC, Darras BT (Eds), Butterworth-Heinemann, Philadelphia 2003. p.633.
  81. Haltia M, Leivo I, Somer H, et al. Muscle-eye-brain disease: a neuropathological study. Ann Neurol 1997; 41:173.
  82. Valanne L, Pihko H, Katevuo K, et al. MRI of the brain in muscle-eye-brain (MEB) disease. Neuroradiology 1994; 36:473.
  83. Kano H, Kobayashi K, Herrmann R, et al. Deficiency of alpha-dystroglycan in muscle-eye-brain disease. Biochem Biophys Res Commun 2002; 291:1283.
  84. Yoshida A, Kobayashi K, Manya H, et al. Muscular dystrophy and neuronal migration disorder caused by mutations in a glycosyltransferase, POMGnT1. Dev Cell 2001; 1:717.
  85. Taniguchi K, Kobayashi K, Saito K, et al. Worldwide distribution and broader clinical spectrum of muscle-eye-brain disease. Hum Mol Genet 2003; 12:527.
  86. Vervoort VS, Holden KR, Ukadike KC, et al. POMGnT1 gene alterations in a family with neurological abnormalities. Ann Neurol 2004; 56:143.
  87. Cormand B, Avela K, Pihko H, et al. Assignment of the muscle-eye-brain disease gene to 1p32-p34 by linkage analysis and homozygosity mapping. Am J Hum Genet 1999; 64:126.
  88. Yanagisawa A, Bouchet C, Quijano-Roy S, et al. POMT2 intragenic deletions and splicing abnormalities causing congenital muscular dystrophy with mental retardation. Eur J Med Genet 2009; 52:201.
  89. Vuillaumier-Barrot S, Quijano-Roy S, Bouchet-Seraphin C, et al. Four Caucasian patients with mutations in the fukutin gene and variable clinical phenotype. Neuromuscul Disord 2009; 19:182.
  90. O'Grady GL, Lek M, Lamande SR, et al. Diagnosis and etiology of congenital muscular dystrophy: We are halfway there. Ann Neurol 2016; 80:101.
  91. Peat RA, Smith JM, Compton AG, et al. Diagnosis and etiology of congenital muscular dystrophy. Neurology 2008; 71:312.
  92. Komaki H, Hayashi YK, Tsuburaya R, et al. Inflammatory changes in infantile-onset LMNA-associated myopathy. Neuromuscul Disord 2011; 21:563.
  93. Gilbreath HR, Castro D, Iannaccone ST. Congenital myopathies and muscular dystrophies. Neurol Clin 2014; 32:689.