Current Neurology and Neuroscience Reports

, Volume 4, Issue 1, pp 51–54 | Cite as

Facioscapulohumeral muscular dystrophy

  • Rabi Tawil
Article

Abstract

Facioscapulohumeral muscular dystrophy (FSHD) is a dominantly inherited muscular dystrophy with a distinctive clinical presentation. Despite the identification of a causal deletion on chromosome 4q35 over a decade ago, the molecular pathophysiology of FSHD remains unclear. The deleted repeats, though clearly associated with FSHD, do not contain expressed genes. The FSHD-associated deletions must, therefore, influence the expression of one or more genes at a distance from the site of the deletion. Recent studies have suggested potential mechanisms through which such a distant effect could be mediated.

Keywords

Muscular Dystrophy Muscle Nerve Creatine Monohydrate 4q35 Gene Facioscapulohumeral Muscular Dystrophy 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References and Recommended Reading

  1. 1.
    Padberg GW: Facioscapulohumeral disease [PhD thesis]. Leiden, The Netherlands: University of Leiden; 1982.Google Scholar
  2. 2.
    Felice KJ, Moore SA: Unusual clinical presentations in patients harboring the facioscapulohumeral dystrophy 4q35 deletion. Muscle Nerve 2001, 24:352–356. Describes the widening clinical spectrum of FSHD since the widespread availability of molecular genetic testing.PubMedCrossRefGoogle Scholar
  3. 3.
    Tawil R, Forrester J, Griggs RC, et al.: Evidence for anticipation and association of deletion size with severity of facioscapulohumeral muscular dystrophy. Ann Neurol 1996, 39:744–748.PubMedCrossRefGoogle Scholar
  4. 4.
    Padberg G, Brouwer OF, de Keizer RJ, et al.: On the significance of retinal vascular disease and hearing loss in facioscapulohumeral muscular dystrophy. Muscle Nerve 1995, 2(suppl):S73-S80.PubMedCrossRefGoogle Scholar
  5. 5.
    Laforet P, de Toma C, Eymard B, et al.: Cardiac involvement in genetically confirmed facioscapulohumeral muscular dystrophy. Neurology 1998, 51:1454–1456.PubMedGoogle Scholar
  6. 6.
    Funakoshi M, Goto K, Arahata K: Epilepsy and mental retardation in a subset of early onset 4q35-associated facioscapulohumeral muscular dystrophy. Neurology 1998, 50:1791–1794.PubMedGoogle Scholar
  7. 7.
    Padberg GW, Frants RR, Brouwere OF, et al.: Facioscapulohumeral muscular dystrophy in the Dutch population. Muscle Nerve 1995, 2(suppl):S81-S84.PubMedCrossRefGoogle Scholar
  8. 8.
    Wijmenga C, Hewitt JE, Sandkuijl LA, et al.: Chromosome 4q DNA rearrangements associated with facioscapulohumeral muscular dystrophy. Nat Genet 1992, 2:26–30.PubMedCrossRefGoogle Scholar
  9. 9.
    Tawil R, Figlewicz DA, Griggs RC, Weiffenbach B: Facioscapulohumeral dystrophy: a distinct regional myopathy with a novel molecular pathogenesis. Ann Neurol 1998, 43:279–282.PubMedCrossRefGoogle Scholar
  10. 10.
    Tim RW, Gilbert JR, Stajich JM, et al.: Clinical studies in nonchromosome 4-linked facioscapulohumeral muscular dystrophy. J Clin Neuromusc Dis 2001, 1:1–7.CrossRefGoogle Scholar
  11. 11.
    Bakker E, Wijmenga C, Vossen RH, et al.: The FSHD linked locus D4F104S1 (p13E 11) on 4q35 has a homologue on 10qter. Muscle Nerve 1995, 2(suppl):S39-S44.PubMedCrossRefGoogle Scholar
  12. 12.
    Deidda G, Cacurri S, Piazzo N, et al.: Direct detection of 4q35 rearrangements implicated in facioscapulohumeral muscular dystrophy (FSHD). J Med Genet 1996, 33:361–365.PubMedCrossRefGoogle Scholar
  13. 13.
    Orrell RW, Tawil R, Forrester J, et al.: Definitive molecular diagnosis of facioscapulohumeral dystrophy. Neurology 1999, 52:1822–1826.PubMedGoogle Scholar
  14. 14.
    Van der Maarel SM, Lemmers RJ: A new dosage test for subtelomeric 4;10 translocations improves conventional diagnosis of facioscapulohumeral muscular dystrophy (FSHD). J Med Genet 1999, 36:823–828.PubMedGoogle Scholar
  15. 15.
    Vitelli F, Villanova M, Malandrini A, et al.: Inheritance of a 38-kb fragment in apparently sporadic facioscapulohumeral muscular dystrophy. Muscle Nerve 1999, 22:1437–1441.PubMedCrossRefGoogle Scholar
  16. 16.
    Lemmers RJ, Osborn M, Haaf T, et al.: D4F104S1 deletion in facioscapulohumeral muscular dystrophy: phenotype, size, and detection. Neurology 2003, 61:178–183. This manuscript describes patients with typical FSHD with deletions that include the p13E-11 probe and even FRG2. This latter finding challenges the notion that upregulation of 4q35 genes is causally important in FSHD.PubMedGoogle Scholar
  17. 17.
    Winokur ST, Bengtsson U, Feddersen J, et al.: The DNA rearrangement associated with facioscapulohumeral muscular dystrophy involves a heterochromatin associated repetitive element: implications for a role of chromatin structure in the pathogenesis of the disease. Chromosome Res 1994, 2:225–234.PubMedCrossRefGoogle Scholar
  18. 18.
    Lunt PW, Jardine PE, Koch MC, et al.: Correlation between fragment size at D4F104S1 and age of onset or at wheelchair use, with a possible generational effect, accounts for much phenotypic variation in 4q35-facioscapulohumeral muscular dystrophy (FSHD). Hum Mol Genet 1995, 4:951–958.PubMedCrossRefGoogle Scholar
  19. 19.
    Lemmers RJ, van der Maarel S, van der Deutekom JC, et al.: Inter- and intrachromosomal subtelomeric rearrangements on 4q35: implications for facioscapulohumeral muscular dystrophy (FSHD) etiology and diagnosis. Hum Mol Genet 1998, 7:1207–1214.PubMedCrossRefGoogle Scholar
  20. 20.
    Tupler R, Berardinelli A, Barbierato L, et al.: Monosomy of distal 4q does not cause facioscapulohumeral muscular dystrophy. J Med Genet 1996, 33:366–370.PubMedGoogle Scholar
  21. 21.
    Gabellini D, Green MR, Tupler R: Inappropriate gene activation in FSHD: a repressor complex binds chromosomal repeat deleted in dystrophic muscle. Cell 2002, 110:339–348. Describes selective upregulation of 4q35 genes and the presence of a repressor complex in the D4Z4 repeats.PubMedCrossRefGoogle Scholar
  22. 22.
    Kaukonen J, Juselius JK, Tiranti V, et al.: Role of adenine nucleotide translocator 1 in mtDNA maintainance. Science 2000, 289:782–785.PubMedCrossRefGoogle Scholar
  23. 23.
    Lemmers RJ, de Kievit P, Sandkuijl L, et al.: Facioscapulohumeral muscular dystrophy is uniquely associated with one of the two variants of the 4q subtelomere. Nat Genet 2002, 32:235–236.PubMedCrossRefGoogle Scholar
  24. 24.
    Bunch WH, Siegel IM: Scapulothoracic arthrodesis in facioscapulohumeral muscular dystrophy. Review of seventeen procedures with three to twenty-one-year follow up. Am J Bone Joint Surg 1993, 75:372–376.Google Scholar
  25. 25.
    Tawil R, McDermott MP, Pandya S, et al.: A pilot study of pednisone in facioscapulohumeral muscular dystrophy. Neurology 1997, 48:46–49.PubMedGoogle Scholar
  26. 26.
    Kissel JT, McDermott MP, Mendell JR, et al., and the FSH-DY Group: Randomized, double-blind, placebo-controlled trial of albuterol in facioscapulohumeral muscular dystrophy. Neurology 2001, 57:1434–1440.PubMedGoogle Scholar
  27. 27.
    Walter MC, Lochmuller H, Reilich P, et al.: Creatine monohydrate in muscular dystrophies: a double-blind placebo-controlled clinical study. Neurology 2000, 54:1848–1850.PubMedGoogle Scholar

Copyright information

© Current Science Inc 2004

Authors and Affiliations

  • Rabi Tawil
    • 1
  1. 1.Department of NeurologyUniversity of Rochester School of Medicine and DentistryRochesterUSA

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