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Distal Myopathies

  • Bjarne UddEmail author
Nerve and Muscle (L Weimer, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Nerve and Muscle

Abstract

Advanced molecular genetic possibilities have made it possible to clarify and delineate an ever growing number of distinct new disease entities in the group of distal myopathies. These diseases share the clinical features of preferential muscle weakness in the feet and/or hands, and as they are genetic disorders that lead to progressive loss of muscle tissue they can also be called distal muscular dystrophies. More than 20 entities are currently identified and many are still waiting for genetic characterisation. No final diagnosis can be made on other grounds than by the molecular genetic defect. Besides the usual investigations, including electromyography and muscle biopsy, muscle imaging is very important in defining the precise pattern of muscle involvement. Based on the combination of age at onset, mode of inheritance, pathology and muscle imaging, the list of possible underlying genes can be tracked down to minimal number allowing for specific genetic testing.

Keywords

Distal myopathy Distal muscular dystrophy Classification Molecular genetics Pathogenesis Diagnostics MRI Muscle pathology 

Notes

Compliance with Ethics Guidelines

Conflict of Interest

Bjarne Udd declares that he has no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References

Papers of particular interest, published recently, have been highlighted as: •• Of major importance

  1. 1.
    Laing NG, Laing BA, Meredith C, et al. Autosomal dominant distal myopathy: linkage to chromosome 14. Am J Hum Genet. 1995;56:422–7.PubMedCentralPubMedGoogle Scholar
  2. 2.
    Welander L. Myopathia distalis tarda hereditaria. Acta Med Scand. 1951;141:1–124.Google Scholar
  3. 3.
    Miyoshi K, Iwasa M, Kawai H. Autosomal recessive distal muscular dystrophy: a new variety of distal muscular dystrophy predominantly seen in Japan. Nippon Rinsho (Tokyo). 1977;35:3922–8.Google Scholar
  4. 4.
    Miyoshi K, Kawai H, Iwasa M, Kusaka K, Nishino H. Autosomal recessive distal muscular dystrophy as a new type of progressive muscular dystrophy. Brain. 1986;109:31–54.PubMedCrossRefGoogle Scholar
  5. 5.
    Nonaka I, Sunohara N, Ishiura S, Satoyoshi E. Familial distal myopathy with rimmed vacuole and lamellar (myeloid) body formation. J Neurol Sci. 1981;51:141–55.PubMedCrossRefGoogle Scholar
  6. 6.
    Udd B, Partanen J, Halonen P, et al. Tibial muscular dystrophy: late adult-onset distal myopathy in 66 Finnish patients. Arch Neurol. 1993;50:604–8.PubMedCrossRefGoogle Scholar
  7. 7.
    Milhorat AT, Wolff HG. Studies in diseases of muscle XIII: progressive muscular dystrophy of atrophic distal type; report of a family; report of autopsy. Arch Neurol Psychiatry. 1943;49:655–64.CrossRefGoogle Scholar
  8. 8.
    Markesbery WR, Griggs RC, Leach RP, Lapham LW. Late onset hereditary distal myopathy. Neurology. 1974;23:127–34.CrossRefGoogle Scholar
  9. 9.
    Bejaoui K, Hirabayashi K, Hentati F, et al. Linkage of Miyoshi myopathy (distal autosomal recessive muscular dystrophy) locus to chromosome 2p12-14. Neurology. 1995;45:768–72.PubMedCrossRefGoogle Scholar
  10. 10.
    Liu J, Aoki M, Illa I, et al. Dysferlin, a novel skeletal muscle gene, is mutation in Miyoshi myopathy and limb girdle muscular dystrophy. Nat Genet. 1998;20:31–6.PubMedCrossRefGoogle Scholar
  11. 11.
    Sjöberg G, Saavedra-Matiz C, Rosen D, et al. A missense mutation in the desmin rod domain is associated with autosomal dominant distal myopathy, and exerts a dominant negative effect on filament formation. Hum Mol Genet. 1999;8:2191–8.PubMedCrossRefGoogle Scholar
  12. 12.
    Haravuori H, Mäkelä-Bengs P, Udd B, et al. Assignment of the tibial muscular dystrophy (TMD) locus on chromosome 2q31. Am J Hum Genet. 1998;62:620–6.PubMedCentralPubMedCrossRefGoogle Scholar
  13. 13.
    Hackman P, Vihola A, Haravuori H, et al. Tibial muscular dystrophy is a titinopathy caused by mutations in TTN, the gene encoding the giant skeletal-muscle protein titin. Am J Hum Genet. 2002;71:492–500.PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Ikeuchi T, Asaka T, Saito M, et al. Gene locus for autosomal recessive distal myopathy with rimmed vacuoles maps to chromosome 9. Ann Neurol. 1997;41:432–7.PubMedCrossRefGoogle Scholar
  15. 15.
    Nishino I, Noguchi S, Murayama K, et al. Distal myopathy with rimmed vacuoles is allelic to hereditary inclusion body myopathy. Neurology. 2002;59:1689–93.PubMedCrossRefGoogle Scholar
  16. 16.
    Meredith C, Herrmann R, Parry C, et al. Mutations in the slow skeletal muscle fiber myosin heavy chain gene (MYH7) cause laing early-onset distal myopathy (MPD1). Am J Hum Genet. 2004;75:703–8.PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    Griggs R, Vihola A, Hackman P, et al. Zaspopathy in a large classic late onset distal myopathy family. Brain. 2007;130:1477–84.PubMedCrossRefGoogle Scholar
  18. 18.
    Ahlberg G, Tell D, Borg K, et al. Genetic linkage of Welander distal myopathy to chromosome 2p13. Ann Neurol. 1999;46:399–404.PubMedCrossRefGoogle Scholar
  19. 19.••
    Hackman P, Sarparanta J, Lehtinen S, et al. Welander distal myopathy is caused by a mutation in the RNA-binding protein TIA1. Ann Neurol. 2012 Dec 13 [Epub ahead of print]. WDM is the hallmark disease for distal myopathies. Linkage of the disease to chromosome 2p was achieved more than 10 years ago and now, finally, the causative gene was identified. The TIA1 gene is not a typical muscle gene at all, and the protein is involved in complex RNA metabolism.Google Scholar
  20. 20.••
    Udd B. Distal myopathies. Neuromusc Disord. 2012;22:5–12. This overview of the different entities of distal myopathies contains the algorithmic flow charts for diagnostic work-up.PubMedCrossRefGoogle Scholar
  21. 21.
    Borg K, Ahlberg G, Anvret M, Edstrom L. Welander distal myopathy: an overview. Neuromuscul Disord. 1998;8:115–8.PubMedCrossRefGoogle Scholar
  22. 22.
    Ahlberg G, Jakobsson F, Fransson A, et al. Distribution of muscle degeneration in Welander distal myopathy: a magnetic resonance imaging and muscle biopsy study. Neuromuscul Disord. 1994;4:55–62.PubMedCrossRefGoogle Scholar
  23. 23.
    Udd B, Kaarianen H, Somer H. Muscular dystrophy with separate clinical phenotypes in a large family. Muscle Nerve. 1991;14:1050–8.PubMedCrossRefGoogle Scholar
  24. 24.
    Udd B, Vihola A, Sarparanta J, Richard I, Hackman P. Titinopathies and extension of the M-line mutation phenotype beyond distal myopathy and LGMD2J. Neurology. 2005;64:636–42.PubMedCrossRefGoogle Scholar
  25. 25.
    Udd B, Lamminen A, Somer H. Imaging methods reveal unexpected patchy lesions in late onset distal myopathy. Neuromusc Disord. 1991;4:279–85.CrossRefGoogle Scholar
  26. 26.
    de Seze J, Udd B, Haravuori H, et al. The first European tibial muscular dystrophy family outside the Finnish population. Neurology. 1998;51:1746–8.PubMedCrossRefGoogle Scholar
  27. 27.
    Van den Bergh P, Bouquiaux O, et al. Tibial muscular dystrophy in a Belgian family. Ann Neurol. 2003;54:248–51.PubMedCrossRefGoogle Scholar
  28. 28.
    Hackman P, Marchand S, Sarparanta J, et al. Truncating mutations in C-terminal titin may cause more severe tibial muscular dystrophy (TMD). Neuromusc Disord. 2008;18:922–8.PubMedCrossRefGoogle Scholar
  29. 29.
    Pollazzon M, Suominen T, Penttilä S, et al. The first Italian family with tibial muscular dystrophy (TMD) caused by a novel titin mutation. J Neurol. 2010;257:575–9.PubMedCrossRefGoogle Scholar
  30. 30.
    Olive M, Goldfarb LG, Shatunov A, et al. Myotilinopathy: refining the clinical and myopathological phenotype. Brain. 2005;128:2315–26.PubMedCrossRefGoogle Scholar
  31. 31.
    Penisson-Besnier I, Dumez C, Chateau D, et al. Autosomal dominant late adult onset distal leg myopathy. Neuromuscul Disord. 1998;8:459–66.PubMedCrossRefGoogle Scholar
  32. 32.
    Penisson-Besnier I, Talvinen K, Dumez C, et al. Myotilinopathy in a family with late onset myopathy. Neuromuscul Disord. 2006;16:427–31.PubMedCrossRefGoogle Scholar
  33. 33.
    Foroud T, Pankratz N, Batchman AP, et al. A mutation in myotilin causes spheroid body myopathy. Neurology. 2005;65:1936–40.PubMedCrossRefGoogle Scholar
  34. 34.
    Claeys K, Udd B, Stoltenburg G. Electron microscopy in myofibrillar myopathies reveals clues to the mutated gene. Neuromusc Disord. 2008;18:656–66.PubMedCrossRefGoogle Scholar
  35. 35.
    Selcen D, Engel AG. Mutations in myotilin cause myofibrillar myopathy. Neurology. 2004;62:1363–71.PubMedCrossRefGoogle Scholar
  36. 36.
    Feit H, Silbergleit A, Schneider L, et al. Vocal cord and pharyngeal weakness with autosomal distal myopathy: clinical description and gene localization to chromosome 5q31. Am J Hum Genet. 1998;63:1732–44.PubMedCentralPubMedCrossRefGoogle Scholar
  37. 37.
    Kraya T, Zierz S. Distal myopathies: from clinical classification to molecular understanding. J Neural Transm. 2013;120 Suppl 1:S3–7.PubMedCrossRefGoogle Scholar
  38. 38.
    Senderek J, Garvey SM, Krieger M, et al. Autosomal-dominant distal myopathy associated with a recurrent missense mutation in the gene encoding the nuclear matrix protein, matrin 3. Am J Hum Genet. 2009;84:511–8.PubMedCentralPubMedCrossRefGoogle Scholar
  39. 39.
    Kimonis V, Mehta S, Fulchiero E, et al. Clinical studies in familial VCP myopathy associated with Paget disease of bone and frontotemporal dementia. Am J Med Genet. 2008;146A:745–57.PubMedCentralPubMedCrossRefGoogle Scholar
  40. 40.
    Johnson J, Mandrioli J, Benatar M, et al. Exome Sequencing Reveals VCP mutations as a cause of familial ALS. Neuron. 2010;68:857–64.PubMedCentralPubMedCrossRefGoogle Scholar
  41. 41.
    Palmio J, Sandell S, Suominen T, Penttilä S, et al. Distinct distal myopathy phenotype caused by VCP gene mutation in a Finnish family. Neuromusc Disord. 2011;21:551–5.PubMedCrossRefGoogle Scholar
  42. 42.
    Vicart P, Caron A, Guicheney P, et al. A missense mutation in the alphaB-crystallin chaperone gene causes a desmin-related myopathy. Nat Genet. 1998;20:92–5.PubMedCrossRefGoogle Scholar
  43. 43.
    Reichlich P, Schoser B, Schramm N, et al. The p.G154S mutation of the alpha-B crystallin gene (CRYAB) causes late-onset distal myopathy. Neuromuscul Disord. 2010;20:255–9.CrossRefGoogle Scholar
  44. 44.
    Walter M, Reichlich P, Hübner A, et al. Identification of a desmin gene mutation in scapuloperoneal syndrome type Kaeser. Neuromusc Disord. 2006;16:708–9.CrossRefGoogle Scholar
  45. 45.
    Bär H, Fischer D, Goudeau H, et al. Pathogenic effects of a novel heterozygous R350P desmin mutation on the assembly of desmin intermediate filaments in vivo and in vitro. Hum Mol Gen. 2005;14:1251–60.PubMedCrossRefGoogle Scholar
  46. 46.
    Palmio J, Penttilä S, Huovinen S, Haapasalo H, Udd B. An unusual phenotype of late-onset desminopathy. Neuromusc Disord. 2013;23:922–3.PubMedCrossRefGoogle Scholar
  47. 47.
    Williams DR, Reardon K, Roberts L, et al. A new dominant distal myopathy affecting posterior leg and anterior upper limb muscles. Neurology. 2005;64:1245–54.PubMedCrossRefGoogle Scholar
  48. 48.••
    Duff R, Tay V, Hackman P, et al. Mutations in the N-terminal actin-binding domain of filamin C (FLNC) cause a distinct distal myopathy. Am J Hum Genet. 2011;88:729–40. The authors have identified a completely new type of distal myopathy. Mutations in FLNC are previously known to cause myofibrillar myopathology with a rather generalised late-onset proximo-distal and axial clinical phenotype of muscle weakness. The mutations causing this new type of disease do not result in myofibrillar myopathology, and this difference is related to the mutations being located in the N-terminal actin binding domain of Filamin-C.PubMedCentralPubMedCrossRefGoogle Scholar
  49. 49.
    Muelas N, Hackman P, Luque H, et al. MYH7 gene tail mutation causing myopathic profiles beyond Laing distal myopathy. Neurology. 2010;75:732–41.PubMedCrossRefGoogle Scholar
  50. 50.
    Lamont P, Udd B, Mastaglia F, et al. Laing early-onset distal myopathy – slow myosin defect with variable abnormalities on muscle biopsy. J Neurol Neurosurg Psychiatry. 2006;77:208–15.PubMedCentralPubMedCrossRefGoogle Scholar
  51. 51.
    Dubourg O, Maisonobe T, Behin A, et al. A novel MYH7 mutation occurring independently in French and Norwegian Laing distal myopathy families and de novo in one Finnish patient. J Neurol. 2011;258:1157–63.PubMedCrossRefGoogle Scholar
  52. 52.
    Cirak S, Deimling F, Sahdev S, et al. Kelch-like homologue 9 mutation is associated with an early onset autosomal dominant distal myopathy. Brain. 2010;133:2123–35.PubMedCentralPubMedCrossRefGoogle Scholar
  53. 53.
    Wallgren-Pettersson C, Lehtokari V-L, Kalimo H, et al. Distal myopathy caused by homozygous missense mutations in the nebulin gene. Brain. 2007;130:1465–76.PubMedCrossRefGoogle Scholar
  54. 54.
    Lehtokari VL, Pelin K, Herczegfalvi A, et al. Nemaline myopathy caused by mutations in the nebulin gene may present as a distal myopathy. Neuromuscul Disord. 2011;21:556–62.PubMedCrossRefGoogle Scholar
  55. 55.
    Eisenberg I, Avidan N, Potikha T, et al. The UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase gene is mutated in recessive hereditary inclusion body myopathy. Nat Genet. 2001;29:83–7.PubMedCrossRefGoogle Scholar
  56. 56.
    Illarioshkin SN, Ivanova-Smolenskaya IA, Greenberg CR, et al. Identical dysferlin mutation in limb-girdle muscular dystrophy type 2B and distal myopathy. Neurology. 2000;55:1931–3.PubMedCrossRefGoogle Scholar
  57. 57.
    Paradas C, Llauger J, Diaz-Manera J, et al. Redefining dysferlinopathy phenotypes based on clinical findings and muscle imaging studies. Neurology. 2010;75:316–23.PubMedCrossRefGoogle Scholar
  58. 58.
    Illa I, Serrano-Munuera C, Gallardo E, et al. Distal anterior compartment myopathy: A dysferlin mutation causing a new muscular dystrophy phenotype. Ann Neurol. 2001;49:130–4.PubMedCrossRefGoogle Scholar
  59. 59.
    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;86:213–21.PubMedCentralPubMedCrossRefGoogle Scholar
  60. 60.••
    Penttilä S, Palmio J, Suominen T, et al. Eight new mutations and the expanding phenotype variability in muscular dystrophy caused by ANO5. Neurology. 2012;78:897–903. The paper describes in good detail the large variation of clinical presentations and disease evolutions involved with anoctaminopathy, including muscle MRI studies. Late-onset proximal limb-girdle muscular dystrophy is more common than early adult-onset distal myopathy. Anoctaminopathy has also been confused with polymyositis.PubMedCrossRefGoogle Scholar
  61. 61.
    Durmus H, Laval S, Deymeer F, et al. Oculopharyngeal distal myopathy is a distinct entity. Neurology. 2011;76:227–35.PubMedCrossRefGoogle Scholar
  62. 62.
    Servidei S, Capon F, Spinazzola M, et al. A distinctive autosomal dominant vacuolar neuromyopathy linked to 19p13. Neurology. 1999;53:830–7.PubMedCrossRefGoogle Scholar
  63. 63.
    Felice KJ, Meredith C, Binz N, et al. Autosomal dominant distal myopathy not linked to the known distal myopathy loci. Neuromuscul Disord. 1999;9:59–65.PubMedCrossRefGoogle Scholar
  64. 64.
    Mahjneh I, Haravuori H, Paetau A, et al. A distinct phenotype of distal myopathy in a large Finnish family. Neurology. 2003;61:87–92.PubMedCrossRefGoogle Scholar
  65. 65.
    Haravuori H, Siitonen A, Mahjneh I, et al. Linkage to two separate loci in a family with a novel distal myopathy phenotype (MPD3). Neuromusc Disord. 2004;14:183–7.PubMedCrossRefGoogle Scholar
  66. 66.
    Linssen WH, de Visser M, Notermans NC, et al. Genetic heterogeneity in Miyoshi-type distal muscular dystrophy. Neuromuscul Disord. 1998;8:317–20.PubMedCrossRefGoogle Scholar
  67. 67.••
    Evilä A, Vihola A, Sarparanta J, et al. Atypical phenotypes in titinopathies explained by second titin mutations and compound heterozygosity. Ann Neurol. 2014 Jan 7 [Epub ahead of print]. The paper opens a new perspective on the phenotype variations repeatedly reported in families with the identical gene mutation in muscular dystrophy. With the example of titinopathy, the authors show that atypical, complex and new phenotypes are associated with second gene mutations on top of a previously well known gene mutation.Google Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Neuromuscular Research CenterTampere University and University HospitalTampereFinland
  2. 2.Folkhalsan Institute of Genetics, Department of Medical Genetics and Haartman InstituteUniversity of HelsinkiHelsinkiFinland
  3. 3.Department of NeurologyVasa Central HospitalVasaFinland

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