title: Limb-girdle and congenital muscular dystrophies: current diagnostics, management, and emerging technologies.
abstract: The muscular dystrophies show muscle degeneration and regeneration (necrotizing myopathy) on muscle biopsy, typically associated with elevated serum creatine kinase, and muscle weakness. In 1986, the first causative gene was identified for the most prevalent and best-characterized form of muscular dystrophy, Duchenne muscular dystrophy. Over the past 25 years, the number of other genes determined to cause different subtypes has grown rapidly. This review gives a synopsis of the 45 genetically defined types of muscular dystrophies and describes the clinical, pathologic, and molecular aspects of each disease. DNA diagnosis remains the most sensitive and specific method for differential diagnosis, but molecular diagnostics can be expensive and complex (because of multiple genes at multiple testing facilities) and reimbursement may be challenging to obtain. However, emerging DNA sequencing technologies (eg, single-molecule third-generation sequencing units) promise to dramatically reduce the complexity and costs of DNA diagnostics. Treatment for nearly all forms remains supportive and is aimed at preventing complications. However, several promising approaches have entered clinical trials, providing tangible hope that quality of life will improve for many patients in the near future.
authors.affiliation: Research Center for Genetic Medicine, Division of Neurology, Department of Pediatrics, Children's National Medical Center, 111 Michigan Avenue Northwest, Washington, DC 20010, USA. ctesiroc@cnmc.org
authors.forename: Carolina Tesi
authors.initials: CT
authors.lastname: Rocha
authors.forename: Eric P
authors.initials: EP
authors.lastname: Hoffman
mesh_terms: D006801:Humans; D049288:Muscular Dystrophies, Limb-Girdle / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D017422:Sequence Analysis, DNA / Q000295:instrumentation / Q000379:methods
references.citation: Muscle Nerve. 2007 Jan;35(1):36-42
references.pmid: 16969838
references.citation: Hum Mutat. 2005 Aug;26(2):165
references.pmid: 16010686
references.citation: Neurology. 2007 Sep 18;69(12):1285-92
references.pmid: 17377071
references.citation: Neuromuscul Disord. 2002 Feb;12(2):187-94
references.pmid: 11738362
references.citation: Nat Genet. 1995 Nov;11(3):257-65
references.pmid: 7581448
references.citation: Hum Mol Genet. 2006 Feb 15;15(4):637-51
references.pmid: 16403804
references.citation: Neurology. 1999 Mar 23;52(5):1015-20
references.pmid: 10102422
references.citation: Ann Neurol. 2006 Nov;60(5):603-10
references.pmid: 17044012
references.citation: Nat Genet. 1998 Sep;20(1):31-6
references.pmid: 9731526
references.citation: Cell. 1994 Aug 26;78(4):625-33
references.pmid: 8069911
references.citation: Lancet Neurol. 2010 Feb;9(2):177-89
references.pmid: 19945914
references.citation: Lab Invest. 2008 Mar;88(3):275-83
references.pmid: 18253147
references.citation: Ann Neurol. 2003 Apr;53(4):537-42
references.pmid: 12666124
references.citation: Neuromuscul Disord. 2005 Mar;15(3):207-17
references.pmid: 15725582
references.citation: Eur J Paediatr Neurol. 2007 Nov;11(6):353-7
references.pmid: 17446099
references.citation: Cell. 1995 Apr 7;81(1):27-40
references.pmid: 7720071
references.citation: Lancet Neurol. 2010 Jan;9(1):77-93
references.pmid: 19945913
references.citation: Am J Hum Genet. 2002 Oct;71(4):739-49
references.pmid: 12192640
references.citation: Brain. 2006 Apr;129(Pt 4):996-1013
references.pmid: 16478798
references.citation: Neuromuscul Disord. 2003 Aug;13(6):508-15
references.pmid: 12899879
references.citation: Hum Mol Genet. 2009 Jan 15;18(2):241-7
references.pmid: 18927124
references.citation: Arq Neuropsiquiatr. 2009 Jun;67(2A):343-62
references.pmid: 19547838
references.citation: Am J Pathol. 2008 Nov;173(5):1476-87
references.pmid: 18832576
references.citation: Brain. 2009 Jan;132(Pt 1):147-55
references.pmid: 19015158
references.citation: Neuromuscul Disord. 2008 Nov;18(11):894-903
references.pmid: 18818076
references.citation: Muscle Nerve. 1998 Jun;21(6):769-75
references.pmid: 9585331
references.citation: Am J Pathol. 2008 Mar;172(3):774-85
references.pmid: 18276788
references.citation: Nat Genet. 1995 Nov;11(3):266-73
references.pmid: 7581449
references.citation: Am J Hum Genet. 2002 Sep;71(3):492-500
references.pmid: 12145747
references.citation: Neuromuscul Disord. 2004 Jan;14(1):56-69
references.pmid: 14659414
references.citation: Nat Genet. 1994 Dec;8(4):323-7
references.pmid: 7894480
references.citation: Neurotherapeutics. 2008 Oct;5(4):627-32
references.pmid: 19019316
references.citation: Muscle Nerve. 2007 Oct;36(4):525-7
references.pmid: 17614318
references.citation: Transplant Proc. 2007 Dec;39(10):3538-40
references.pmid: 18089432
references.citation: Arq Neuropsiquiatr. 2009 Mar;67(1):144-68
references.pmid: 19330236
references.citation: Nat Genet. 1996 Oct;14(2):195-8
references.pmid: 8841194
references.citation: Hum Mol Genet. 2000 Sep 1;9(14):2141-7
references.pmid: 10958653
references.citation: Hum Mol Genet. 2001 Dec 1;10(25):2851-9
references.pmid: 11741828
references.citation: Nat Genet. 1998 Sep;20(1):37-42
references.pmid: 9731527
references.citation: Nature. 2007 May 3;447(7140):87-91
references.pmid: 17450125
references.citation: Hum Mol Genet. 2003 Oct 15;12 Spec No 2:R259-64
references.pmid: 12925572
references.citation: J Cell Biol. 2009 Jan 12;184(1):31-44
references.pmid: 19124654
references.citation: Muscle Nerve. 2004 Feb;29(2):292-9
references.pmid: 14755496
references.citation: Am J Hum Genet. 1999 Jun;64(6):1524-40
references.pmid: 10330340
references.citation: Ann Neurol. 2009 Jun;65(6):667-76
references.pmid: 19288467
references.citation: Science. 1995 Nov 3;270(5237):819-22
references.pmid: 7481775