Journal of Pediatric Neurology 2018; 16(04): 222-231
DOI: 10.1055/s-0037-1604197
Review Article
Georg Thieme Verlag KG Stuttgart · New York

A Pediatric Review of Facioscapulohumeral Muscular Dystrophy

Jean K. Mah
1   Department of Pediatrics and Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
,
Yi-Wen Chen
2   Center for Genetic Medicine Research, Children's National Health System, Washington, District of Columbia, United States
3   Department of Integrative Systems Biology, George Washington University, Washington, District of Columbia, United States
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Weitere Informationen

Publikationsverlauf

10. März 2017

02. Juni 2017

Publikationsdatum:
17. Juli 2017 (online)

Abstract

Facioscapulohumeral dystrophy is one of the most common forms of muscular dystrophies worldwide. It is a complex and heterogeneous disease secondary to insufficient epigenetic repression of D4Z4 repeats and aberrant expression of DUX4 in skeletal muscles. Type 1 facioscapulohumeral muscular dystrophy (FSHD) is caused by contraction of D4Z4 repeats on 4q35, whereas type 2 FSHD is associated with mutations of the SMCHD1 or DNMT3B gene in the presence of a disease-permissive 4qA haplotype. Classical FSHD is a slowly progressive disorder with gradual-onset of muscle atrophy and a descending pattern of muscle weakness. In contrast, early-onset FSHD is associated with a large deletion of D4Z4 repeats and a more severe disease phenotype, including early loss of independent ambulation as well as extramuscular manifestations, such as retinal vasculopathy, hearing loss, and central nervous system (CNS) involvement. However, the correlation between D4Z4 repeats and disease severity remains imprecise. The current standard of care guidelines offers comprehensive assessment and symptomatic management of secondary complications. Several clinical trials are currently underway for FSHD. New and emerging treatments focus on correcting the transcriptional misregulation of D4Z4 and reversing the cytotoxic effects of DUX4. Other potential therapeutic targets include reduction of inflammation, improving muscle mass, and activating compensatory molecular pathways. The utility of disease-modifying treatments will depend on selection of sensitive clinical endpoints as well as validation of muscle magnetic resonance imaging (MRI) and other biomarkers to detect meaningful changes in disease progression. Correction of the epigenetic defects using new gene editing as well as other DUX4 silencing technologies offers potential treatment options for many individuals with FSHD.

 
  • References

  • 1 Tawil R, van der Maarel SM, Tapscott SJ. Facioscapulohumeral dystrophy: the path to consensus on pathophysiology. Skelet Muscle 2014; 4: 12
  • 2 Sacconi S, Salviati L, Desnuelle C. Facioscapulohumeral muscular dystrophy. Biochim Biophys Acta 2015; 1852 (04) 607-614
  • 3 Daxinger L, Tapscott SJ, van der Maarel SM. Genetic and epigenetic contributors to FSHD. Curr Opin Genet Dev 2015; 33: 56-61
  • 4 Knopp P, Krom YD, Banerji CR. , et al. DUX4 induces a transcriptome more characteristic of a less-differentiated cell state and inhibits myogenesis. J Cell Sci 2016; 129 (20) 3816-3831
  • 5 Flanigan KM, Coffeen CM, Sexton L, Stauffer D, Brunner S, Leppert MF. Genetic characterization of a large, historically significant Utah kindred with facioscapulohumeral dystrophy. Neuromuscul Disord 2001; 11 (6–7): 525-529
  • 6 Deenen JC, Arnts H, van der Maarel SM. , et al. Population-based incidence and prevalence of facioscapulohumeral dystrophy. Neurology 2014; 83 (12) 1056-1059
  • 7 Padberg GW, Frants RR, Brouwer OF, Wijmenga C, Bakker E, Sandkuijl LA. Facioscapulohumeral muscular dystrophy in the Dutch population. Muscle Nerve Suppl 1995; 2: S81-S84
  • 8 Padberg GW, Lunt PW, Koch M, Fardeau M. Diagnostic criteria for facioscapulohumeral muscular dystrophy. Neuromuscul Disord 1991; 1 (04) 231-234
  • 9 Lemmers RJ, Wohlgemuth M, van der Gaag KJ. , et al. Specific sequence variations within the 4q35 region are associated with facioscapulohumeral muscular dystrophy. Am J Hum Genet 2007; 81 (05) 884-894
  • 10 Scionti I, Fabbri G, Fiorillo C. , et al. Facioscapulohumeral muscular dystrophy: new insights from compound heterozygotes and implication for prenatal genetic counselling. J Med Genet 2012; 49 (03) 171-178
  • 11 van der Maarel SM, Deidda G, Lemmers RJ. , et al. De novo facioscapulohumeral muscular dystrophy: frequent somatic mosaicism, sex-dependent phenotype, and the role of mitotic transchromosomal repeat interaction between chromosomes 4 and 10. Am J Hum Genet 2000; 66 (01) 26-35
  • 12 Tawil R, McDermott MP, Mendell JR, Kissel J, Griggs RC. ; FSH-DY Group. Facioscapulohumeral muscular dystrophy (FSHD): design of natural history study and results of baseline testing. Neurology 1994; 44 (3, Pt 1): 442-446
  • 13 Pradhan S. Poly-Hill sign in facioscapulohumeral dystrophy. Muscle Nerve 2002; 25 (05) 754-755
  • 14 Shahrizaila N, Wills AJ. Significance of Beevor's sign in facioscapulohumeral dystrophy and other neuromuscular diseases. J Neurol Neurosurg Psychiatry 2005; 76 (06) 869-870
  • 15 Mul K, Lassche S, Voermans NC, Padberg GW, Horlings CG, van Engelen BG. What's in a name? The clinical features of facioscapulohumeral muscular dystrophy. Pract Neurol 2016; 16 (03) 201-207
  • 16 van der Kooi EL, Kalkman JS, Lindeman E. , et al. Effects of training and albuterol on pain and fatigue in facioscapulohumeral muscular dystrophy. J Neurol 2007; 254 (07) 931-940
  • 17 Pastorello E, Cao M, Trevisan CP. Atypical onset in a series of 122 cases with Facioscapulohumeral muscular dystrophy. Clin Neurol Neurosurg 2012; 114 (03) 230-234
  • 18 van der Kooi AJ, Visser MC, Rosenberg N. , et al. Extension of the clinical range of facioscapulohumeral dystrophy: report of six cases. J Neurol Neurosurg Psychiatry 2000; 69 (01) 114-116
  • 19 Wohlgemuth M, de Swart BJ, Kalf JG, Joosten FB, Van der Vliet AM, Padberg GW. Dysphagia in facioscapulohumeral muscular dystrophy. Neurology 2006; 66 (12) 1926-1928
  • 20 van Dijk GP, van der Kooi E, Behin A. , et al. High prevalence of incomplete right bundle branch block in facioscapulohumeral muscular dystrophy without cardiac symptoms. Funct Neurol 2014; 29 (03) 159-165
  • 21 Tsuji M, Kinoshita M, Imai Y, Kawamoto M, Kohara N. Facioscapulohumeral muscular dystrophy presenting with hypertrophic cardiomyopathy: a case study. Neuromuscul Disord 2009; 19 (02) 140-142
  • 22 Scully MA, Eichinger KJ, Donlin-Smith CM, Tawil R, Statland JM. Restrictive lung involvement in facioscapulohumeral muscular dystrophy. Muscle Nerve 2014; 50 (05) 739-743
  • 23 Sacconi S, Salviati L, Bourget I. , et al. Diagnostic challenges in facioscapulohumeral muscular dystrophy. Neurology 2006; 67 (08) 1464-1466
  • 24 Jensen MP, Hoffman AJ, Stoelb BL, Abresch RT, Carter GT, McDonald CM. Chronic pain in persons with myotonic dystrophy and facioscapulohumeral dystrophy. Arch Phys Med Rehabil 2008; 89 (02) 320-328
  • 25 Statland JM, Tawil R. Risk of functional impairment in facioscapulohumeral muscular dystrophy. Muscle Nerve 2014; 49 (04) 520-527
  • 26 Dorobek M, van der Maarel SM, Lemmers RJ. , et al. Early-onset facioscapulohumeral muscular dystrophy type 1 with some atypical features. J Child Neurol 2015; 30 (05) 580-587
  • 27 Klinge L, Eagle M, Haggerty ID, Roberts CE, Straub V, Bushby KM. Severe phenotype in infantile facioscapulohumeral muscular dystrophy. Neuromuscul Disord 2006; 16 (09–10): 553-558
  • 28 Brooke MH. A Clinician's View of Neuromuscular Diseases. Baltimore, MD: Williams & Wilkins; 1977
  • 29 Brouwer OF, Padberg GW, Wijmenga C, Frants RR. Facioscapulohumeral muscular dystrophy in early childhood. Arch Neurol 1994; 51 (04) 387-394
  • 30 Chen TH, Lai YH, Lee PL. , et al. Infantile facioscapulohumeral muscular dystrophy revisited: Expansion of clinical phenotypes in patients with a very short EcoRI fragment. Neuromuscul Disord 2013; 23 (04) 298-305
  • 31 Hanson PA, Rowland LP. Möbius syndrome and facioscapulohumeral muscular dystrophy. Arch Neurol 1971; 24 (01) 31-39
  • 32 Kolski HK, Leonard NJ, Lemmers RJ, Bamforth JS. Atypical facet of Möbius syndrome: association with facioscapulohumeral muscular dystrophy. Muscle Nerve 2008; 37 (04) 526-529
  • 33 Statland JM, Sacconi S, Farmakidis C, Donlin-Smith CM, Chung M, Tawil R. Coats syndrome in facioscapulohumeral dystrophy type 1: frequency and D4Z4 contraction size. Neurology 2013; 80 (13) 1247-1250
  • 34 Grosso S, Mostardini R, Di Bartolo RM, Balestri P, Verrotti A. Epilepsy, speech delay, and mental retardation in facioscapulohumeral muscular dystrophy. Eur J Paediatr Neurol 2011; 15 (05) 456-460
  • 35 Lutz KL, Holte L, Kliethermes SA, Stephan C, Mathews KD. Clinical and genetic features of hearing loss in facioscapulohumeral muscular dystrophy. Neurology 2013; 81 (16) 1374-1377
  • 36 Bindoff LA, Mjellem N, Sommerfelt K. , et al. Severe fascioscapulohumeral muscular dystrophy presenting with Coats' disease and mental retardation. Neuromuscul Disord 2006; 16 (9–10): 559-563
  • 37 Lunt PW, Jardine PE, Koch MC. , et al. Correlation between fragment size at D4F104S1 and age at 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 (05) 951-958
  • 38 Tawil R, Kissel JT, Heatwole C, Pandya S, Gronseth G, Benatar M. ; Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology; Practice Issues Review Panel of the American Association of Neuromuscular & Electrodiagnostic Medicine. Evidence-based guideline summary: evaluation, diagnosis, and management of facioscapulohumeral muscular dystrophy: report of the guideline development, dissemination, and implementation subcommittee of the American Academy of Neurology and the Practice Issues Review Panel of the American Association of Neuromuscular & Electrodiagnostic Medicine. Neurology 2015; 85 (04) 357-364
  • 39 Goselink RJ, Schreuder TH, Mul K. , et al. Facioscapulohumeral dystrophy in children: design of a prospective, observational study on natural history, predictors and clinical impact (iFocus FSHD). BMC Neurol 2016; 16: 138
  • 40 Nikolic A, Ricci G, Sera F. , et al. Clinical expression of facioscapulohumeral muscular dystrophy in carriers of 1-3 D4Z4 reduced alleles: experience of the FSHD Italian National Registry. BMJ Open 2016; 6 (01) e007798
  • 41 van Deutekom JC, Wijmenga C, van Tienhoven EA. , et al. FSHD associated DNA rearrangements are due to deletions of integral copies of a 3.2 kb tandemly repeated unit. Hum Mol Genet 1993; 2 (12) 2037-2042
  • 42 van Overveld PG, Lemmers RJ, Sandkuijl LA. , et al. Hypomethylation of D4Z4 in 4q-linked and non-4q-linked facioscapulohumeral muscular dystrophy. Nat Genet 2003; 35 (04) 315-317
  • 43 Lemmers RJ, Tawil R, Petek LM. , et al. Digenic inheritance of an SMCHD1 mutation and an FSHD-permissive D4Z4 allele causes facioscapulohumeral muscular dystrophy type 2. Nat Genet 2012; 44 (12) 1370-1374
  • 44 van den Boogaard ML, Lemmers RJ, Balog J. , et al. Mutations in DNMT3B Modify epigenetic repression of the D4Z4 repeat and the penetrance of facioscapulohumeral dystrophy. Am J Hum Genet 2016; 98 (05) 1020-1029
  • 45 Gabriëls J, Beckers MC, Ding H. , et al. Nucleotide sequence of the partially deleted D4Z4 locus in a patient with FSHD identifies a putative gene within each 3.3 kb element. Gene 1999; 236 (01) 25-32
  • 46 Ansseau E, Laoudj-Chenivesse D, Marcowycz A. , et al. DUX4c is up-regulated in FSHD. It induces the MYF5 protein and human myoblast proliferation. PLoS One 2009; 4 (10) e7482
  • 47 Ostlund C, Garcia-Carrasquillo RM, Belayew A, Worman HJ. Intracellular trafficking and dynamics of double homeodomain proteins. Biochemistry 2005; 44 (07) 2378-2384
  • 48 Coppée F, Mattéotti C, Ansseau E. , et al. The DUX gene family and FSHD. In: Upadhyaya M, Cooper DN. , eds. Facioscapulohumeral Muscular Dystrophy: Clinical Medicine and Molecular Cell Biology. Oxford, UK: BIOS Scientific Publishers; 2004
  • 49 Yip DJ, Picketts DJ. Increasing D4Z4 repeat copy number compromises C2C12 myoblast differentiation. FEBS Lett 2003; 537 (1–3): 133-138
  • 50 Beckers M, Gabriëls J, van der Maarel S. , et al. Active genes in junk DNA? Characterization of DUX genes embedded within 3.3 kb repeated elements. Gene 2001; 264 (01) 51-57
  • 51 Sharma V, Harafuji N, Belayew A, Chen YW. DUX4 differentially regulates transcriptomes of human rhabdomyosarcoma and mouse C2C12 cells. PLoS One 2013; 8 (05) e64691
  • 52 Geng LN, Yao Z, Snider L. , et al. DUX4 activates germline genes, retroelements, and immune mediators: implications for facioscapulohumeral dystrophy. Dev Cell 2012; 22 (01) 38-51
  • 53 Winokur ST, Chen YW, Masny PS. , et al. Expression profiling of FSHD muscle supports a defect in specific stages of myogenic differentiation. Hum Mol Genet 2003; 12 (22) 2895-2907
  • 54 Ansseau E, Eidahl JO, Lancelot C. , et al. Homologous transcription factors DUX4 and DUX4c associate with cytoplasmic proteins during muscle differentiation. PLoS One 2016; 11 (01) e0146893
  • 55 Lemmers RJ, van der Vliet PJ, Klooster R. , et al. A unifying genetic model for facioscapulohumeral muscular dystrophy. Science 2010; 329 (5999): 1650-1653
  • 56 Larsen M, Rost S, El Hajj N. , et al. Diagnostic approach for FSHD revisited: SMCHD1 mutations cause FSHD2 and act as modifiers of disease severity in FSHD1. Eur J Hum Genet 2015; 23 (06) 808-816
  • 57 Sacconi S, Lemmers RJ, Balog J. , et al. The FSHD2 gene SMCHD1 is a modifier of disease severity in families affected by FSHD1. Am J Hum Genet 2013; 93 (04) 744-751
  • 58 Lemmers RJ, O'Shea S, Padberg GW, Lunt PW, van der Maarel SM. Best practice guidelines on genetic diagnostics of facioscapulohumeral muscular dystrophy: workshop 9th June 2010, LUMC, Leiden, The Netherlands. Neuromuscul Disord 2012; 22 (05) 463-470
  • 59 Calandra P, Cascino I, Lemmers RJ. , et al. Allele-specific DNA hypomethylation characterises FSHD1 and FSHD2. J Med Genet 2016; 53 (05) 348-355
  • 60 Tawil R, van der Maarel S, Padberg GW, van Engelen BG. 171st ENMC international workshop: Standards of care and management of facioscapulohumeral muscular dystrophy. Neuromuscul Disord 2010; 20 (07) 471-475
  • 61 Small RG. Coats' disease and muscular dystrophy. Trans Am Acad Ophthalmol Otolaryngol 1968; 72 (02) 225-231
  • 62 Akiyama C, Suzuki H, Nonaka I. A case of facioscapulohumeral muscular dystrophy with infantile spasms, sensorineural deafness and retinal vessel abnormality [Article in Japanese]. No To Hattatsu 1991; 23 (04) 395-399
  • 63 Miura K, Kumagai T, Matsumoto A. , et al. Two cases of chromosome 4q35-linked early onset facioscapulohumeral muscular dystrophy with mental retardation and epilepsy. Neuropediatrics 1998; 29 (05) 239-241
  • 64 Funakoshi M, Goto K, Arahata K. Epilepsy and mental retardation in a subset of early onset 4q35-facioscapulohumeral muscular dystrophy. Neurology 1998; 50 (06) 1791-1794
  • 65 Hobson-Webb LD, Caress JB. Facioscapulohumeral muscular dystrophy can be a cause of isolated childhood cognitive dysfunction. J Child Neurol 2006; 21 (03) 252-253
  • 66 Trevisan CP, Pastorello E, Tomelleri G. , et al. Facioscapulohumeral muscular dystrophy: hearing loss and other atypical features of patients with large 4q35 deletions. Eur J Neurol 2008; 15 (12) 1353-1358
  • 67 Saito Y, Miyashita S, Yokoyama A. , et al. Facioscapulohumeral muscular dystrophy with severe mental retardation and epilepsy. Brain Dev 2007; 29 (04) 231-233
  • 68 Trucco F, Pedemonte M, Fiorillo C. , et al. Respiratory pattern in a FSHD pediatric population. Respir Med 2016; 119: 78-80
  • 69 Escolar DM, Henricson EK, Mayhew J. , et al. Clinical evaluator reliability for quantitative and manual muscle testing measures of strength in children. Muscle Nerve 2001; 24 (06) 787-793
  • 70 Eichinger K, Heatwole C, Heininger S. , et al; FSHD Clinical Trials Research Network. Validity of the 6 minute walk test in facioscapulohumeral muscular dystrophy. Muscle Nerve 2017; 55 (03) 333-337
  • 71 Lamperti C, Fabbri G, Vercelli L. , et al. A standardized clinical evaluation of patients affected by facioscapulohumeral muscular dystrophy: the FSHD clinical score. Muscle Nerve 2010; 42 (02) 213-217
  • 72 Ricci G, Ruggiero L, Vercelli L. , et al. A novel clinical tool to classify facioscapulohumeral muscular dystrophy phenotypes. J Neurol 2016; 263 (06) 1204-1214
  • 73 Tasca G, Monforte M, Ottaviani P. , et al. Magnetic resonance imaging in a large cohort of facioscapulohumeral muscular dystrophy patients: pattern refinement and implications for clinical trials. Ann Neurol 2016; 79 (05) 854-864
  • 74 Gerevini S, Scarlato M, Maggi L. , et al. Muscle MRI findings in facioscapulohumeral muscular dystrophy. Eur Radiol 2016; 26 (03) 693-705
  • 75 Matsuzaka Y, Kishi S, Aoki Y. , et al. Three novel serum biomarkers, miR-1, miR-133a, and miR-206 for limb-girdle muscular dystrophy, facioscapulohumeral muscular dystrophy, and Becker muscular dystrophy. Environ Health Prev Med 2014; 19 (06) 452-458
  • 76 Statland J, Donlin-Smith CM, Tapscott SJ, van der Maarel S, Tawil R. Multiplex screen of serum biomarkers in facioscapulohumeral muscular dystrophy. J Neuromuscul Dis 2014; 1 (02) 181-190
  • 77 Petek LM, Rickard AM, Budech C. , et al. A cross sectional study of two independent cohorts identifies serum biomarkers for facioscapulohumeral muscular dystrophy (FSHD). Neuromuscul Disord 2016; 26 (07) 405-413
  • 78 Snider L, Geng LN, Lemmers RJ. , et al. Facioscapulohumeral dystrophy: incomplete suppression of a retrotransposed gene. PLoS Genet 2010; 6 (10) e1001181
  • 79 Tasca G, Pescatori M, Monforte M. , et al. Different molecular signatures in magnetic resonance imaging-staged facioscapulohumeral muscular dystrophy muscles. PLoS One 2012; 7 (06) e38779
  • 80 Rahimov F, King OD, Leung DG. , et al. Transcriptional profiling in facioscapulohumeral muscular dystrophy to identify candidate biomarkers. Proc Natl Acad Sci U S A 2012; 109 (40) 16234-16239
  • 81 Wallace LM, Garwick SE, Mei W. , et al. DUX4, a candidate gene for facioscapulohumeral muscular dystrophy, causes p53-dependent myopathy in vivo. Ann Neurol 2011; 69 (03) 540-552
  • 82 Wuebbles RD, Long SW, Hanel ML, Jones PL. Testing the effects of FSHD candidate gene expression in vertebrate muscle development. Int J Clin Exp Pathol 2010; 3 (04) 386-400
  • 83 Kowaljow V, Marcowycz A, Ansseau E. , et al. The DUX4 gene at the FSHD1A locus encodes a pro-apoptotic protein. Neuromuscul Disord 2007; 17 (08) 611-623
  • 84 Winokur ST, Barrett K, Martin JH. , et al. Facioscapulohumeral muscular dystrophy (FSHD) myoblasts demonstrate increased susceptibility to oxidative stress. Neuromuscul Disord 2003; 13 (04) 322-333
  • 85 Turki A, Hayot M, Carnac G. , et al. Functional muscle impairment in facioscapulohumeral muscular dystrophy is correlated with oxidative stress and mitochondrial dysfunction. Free Radic Biol Med 2012; 53 (05) 1068-1079
  • 86 Feng Q, Snider L, Jagannathan S. , et al. A feedback loop between nonsense-mediated decay and the retrogene DUX4 in facioscapulohumeral muscular dystrophy. eLife 2015; DOI: 10.7554/eLife.04996.
  • 87 Rickard AM, Petek LM, Miller DG. Endogenous DUX4 expression in FSHD myotubes is sufficient to cause cell death and disrupts RNA splicing and cell migration pathways. Hum Mol Genet 2015; 24 (20) 5901-5914
  • 88 Homma S, Beermann ML, Boyce FM, Miller JB. Expression of FSHD-related DUX4-FL alters proteostasis and induces TDP-43 aggregation. Ann Clin Transl Neurol 2015; 2 (02) 151-166
  • 89 Vanderplanck C, Ansseau E, Charron S. , et al. The FSHD atrophic myotube phenotype is caused by DUX4 expression. PLoS One 2011; 6 (10) e26820
  • 90 Pandey SN, Lee YC, Yokota T, Chen YW. Morpholino treatment improves muscle function and pathology of Pitx1 transgenic mice. Mol Ther 2014; 22 (02) 390-396
  • 91 Moreno PM, Pêgo AP. Therapeutic antisense oligonucleotides against cancer: hurdling to the clinic. Front Chem 2014; 2: 87
  • 92 Thakker DR, Natt F, Hüsken D. , et al. Neurochemical and behavioral consequences of widespread gene knockdown in the adult mouse brain by using nonviral RNA interference. Proc Natl Acad Sci U S A 2004; 101 (49) 17270-17275
  • 93 Bortolanza S, Nonis A, Sanvito F. , et al. AAV6-mediated systemic shRNA delivery reverses disease in a mouse model of facioscapulohumeral muscular dystrophy. Mol Ther 2011; 19 (11) 2055-2064
  • 94 Wallace LM, Garwick-Coppens SE, Tupler R, Harper SQ. RNA interference improves myopathic phenotypes in mice over-expressing FSHD region gene 1 (FRG1). Mol Ther 2011; 19 (11) 2048-2054
  • 95 Wallace LM, Liu J, Domire JS. , et al. RNA interference inhibits DUX4-induced muscle toxicity in vivo: implications for a targeted FSHD therapy. Mol Ther 2012; 20 (07) 1417-1423
  • 96 Gabellini D, Green MR, Tupler R. Inappropriate gene activation in FSHD: a repressor complex binds a chromosomal repeat deleted in dystrophic muscle. Cell 2002; 110 (03) 339-348
  • 97 Chen JC, King OD, Zhang Y. , et al. Morpholino-mediated knockdown of DUX4 toward facioscapulohumeral muscular dystrophy therapeutics. Mol Ther 2016; 24 (08) 1405-1411
  • 98 Frisullo G, Frusciante R, Nociti V. , et al. CD8(+) T cells in facioscapulohumeral muscular dystrophy patients with inflammatory features at muscle MRI. J Clin Immunol 2011; 31 (02) 155-166
  • 99 Hengstman GJ, van Brenk L, Vree Egberts WT. , et al. High specificity of myositis specific autoantibodies for myositis compared with other neuromuscular disorders. J Neurol 2005; 252 (05) 534-537
  • 100 Tawil R, McDermott MP, Pandya S. , et al; FSH-DY Group. A pilot trial of prednisone in facioscapulohumeral muscular dystrophy. Neurology 1997; 48 (01) 46-49
  • 101 Lo WS, Gardiner E, Xu Z. , et al. Human tRNA synthetase catalytic nulls with diverse functions. Science 2014; 345 (6194): 328-332
  • 102 Zhou JJ, Wang F, Xu Z. , et al. Secreted histidyl-tRNA synthetase splice variants elaborate major epitopes for autoantibodies in inflammatory myositis. J Biol Chem 2014; 289 (28) 19269-19275
  • 103 Rodriguez J, Vernus B, Chelh I. , et al. Myostatin and the skeletal muscle atrophy and hypertrophy signaling pathways. Cell Mol Life Sci 2014; 71 (22) 4361-4371
  • 104 Babcock LW, Knoblauch M, Clarke MS. The role of myostatin and activin receptor IIB in the regulation of unloading-induced myofiber type-specific skeletal muscle atrophy. J Appl Physiol (1985) 2015; 119 (06) 633-642
  • 105 Jespersen JG, Nedergaard A, Andersen LL, Schjerling P, Andersen JL. Myostatin expression during human muscle hypertrophy and subsequent atrophy: increased myostatin with detraining. Scand J Med Sci Sports 2011; 21 (02) 215-223
  • 106 Durieux AC, Amirouche A, Banzet S. , et al. Ectopic expression of myostatin induces atrophy of adult skeletal muscle by decreasing muscle gene expression. Endocrinology 2007; 148 (07) 3140-3147
  • 107 Kirk S, Oldham J, Kambadur R, Sharma M, Dobbie P, Bass J. Myostatin regulation during skeletal muscle regeneration. J Cell Physiol 2000; 184 (03) 356-363
  • 108 Chen YW, Nagaraju K, Bakay M. , et al. Early onset of inflammation and later involvement of TGFbeta in Duchenne muscular dystrophy. Neurology 2005; 65 (06) 826-834
  • 109 Latres E, Pangilinan J, Miloscio L. , et al. Myostatin blockade with a fully human monoclonal antibody induces muscle hypertrophy and reverses muscle atrophy in young and aged mice. Skelet Muscle 2015; 5: 34
  • 110 Zhang L, Rajan V, Lin E. , et al. Pharmacological inhibition of myostatin suppresses systemic inflammation and muscle atrophy in mice with chronic kidney disease. FASEB J 2011; 25 (05) 1653-1663
  • 111 Gilson H, Schakman O, Combaret L. , et al. Myostatin gene deletion prevents glucocorticoid-induced muscle atrophy. Endocrinology 2007; 148 (01) 452-460
  • 112 Holzbaur EL, Howland DS, Weber N. , et al. Myostatin inhibition slows muscle atrophy in rodent models of amyotrophic lateral sclerosis. Neurobiol Dis 2006; 23 (03) 697-707
  • 113 Wagner KR, McPherron AC, Winik N, Lee SJ. Loss of myostatin attenuates severity of muscular dystrophy in mdx mice. Ann Neurol 2002; 52 (06) 832-836
  • 114 Wagner KR, Fleckenstein JL, Amato AA. , et al. A phase I/IItrial of MYO-029 in adult subjects with muscular dystrophy. Ann Neurol 2008; 63 (05) 561-571
  • 115 Moyle LA, Blanc E, Jaka O. , et al. Ret function in muscle stem cells points to tyrosine kinase inhibitor therapy for facioscapulohumeral muscular dystrophy. eLife 2016; 5: 1-35 . Doi: 10.7554/eLife.11405.001
  • 116 Sharma V, Pandey SN, Khawaja H, Brown KJ, Hathout Y, Chen YW. PARP1 differentially interacts with promoter region of DUX4 gene in FSHD myoblasts. J Genet Syndr Gene Ther 2016; 7 (04) 7
  • 117 Emilie P, Maurice H, Gilles C, Joel P, Jacques M, Dalila C. Oxidative stress and dystrophy facioscapulohumeral: effects of vitamin C, vitamin E, zinc gluconate and selenomethionine supplementation. Free Radic Biol Med 2014; 75 (Suppl. 01) S14
  • 118 Passerieux E, Hayot M, Jaussent A. , et al. Effects of vitamin C, vitamin E, zinc gluconate, and selenomethionine supplementation on muscle function and oxidative stress biomarkers in patients with facioscapulohumeral dystrophy: a double-blind randomized controlled clinical trial. Free Radic Biol Med 2015; 81: 158-169
  • 119 Voet N, Bleijenberg G, Hendriks J. , et al. Both aerobic exercise and cognitive-behavioral therapy reduce chronic fatigue in FSHD: an RCT. Neurology 2014; 83 (21) 1914-1922
  • 120 Bankolé LC, Millet GY, Temesi J. , et al. Safety and efficacy of a 6-month home-based exercise program in patients with facioscapulohumeral muscular dystrophy: a randomized controlled trial. Medicine (Baltimore) 2016; 95 (31) e4497
  • 121 Pasotti S, Magnani B, Longa E. , et al. An integrated approach in a case of facioscapulohumeral dystrophy. BMC Musculoskelet Disord 2014; 15: 155
  • 122 Dib C, Bou Saada Y, Dmitriev P. , et al. Correction of the FSHD myoblast differentiation defect by fusion with healthy myoblasts. J Cell Physiol 2016; 231 (01) 62-71
  • 123 Himeda CL, Jones TI, Jones PL. CRISPR/dCas9-mediated transcriptional inhibition ameliorates the epigenetic dysregulation at D4Z4 and represses DUX4-fl in FSH muscular dystrophy. Mol Ther 2016; 24 (03) 527-535