EDITORIAL
Muscle Nerve 50: 721–722, 2014
MAKING SENSE OF THE MUSCULAR DYSTROPHIES: DIAGNOSIS AND TREATMENT GUIDELINE FOR LIMB-GIRDLE MUSCULAR DYSTROPHY JOHN D. ENGLAND, MD Department of Neurology, School of Medicine, Louisiana State University Health Sciences Center, 1542 Tulane Avenue, New Orleans, Louisiana, 70112, USA
The limb-girdle muscular dystrophies (LGMDs) are a heterogeneous group of genetically determined myopathies. In 1954, Walton and Nattrass proposed LGMD as a distinct clinical phenotype to differentiate it from the 3 most common muscular dystrophies (myotonic, Duchenne, and facioscapulohumeral).1 For the most part, the clinical phenotype of predominantly proximal muscle weakness involving pelvic and shoulder girdle muscles remains valid, but genetic diagnosis has widened the clinical phenotype to include other patterns of weakness. For instance, some patients have predominantly distal or even scapuloperoneal patterns of weakness. Diagnosis of LGMD now rests upon genetic analysis, and this has demonstrated that LGMD can exhibit striking phenotypic and genetic variability. The current nomenclature, which was established in 1995, divides LGMD into autosomal dominant (LGMD1) and autosomal recessive (LGMD2) types.2,3 Additional subtypes are designated by an alphabetical lettering system (e.g., LGMD1A, LGMD1B, etc.), which is based upon the order of discovery for each genetic subtype. At this time, there are 8 well-defined autosomal dominant (LGMD1A-1H) and 19 well-defined autosomal recessive (LGMD2A-2S) subtypes. Undoubtedly, more will be described. Although the most prevalent subtypes are LGMD2A (calpain-3), LGMD2B (dysferlin), LGMD2C-2F (sarcoglycans), and LGMD2I (fukutin-related protein), the complexity of the LGMDs has become rather staggering. Even for most neuromuscular experts, keeping current in the field is difficult. Because of the importance and complexity of the muscular dystrophies, the American Association of Neuromuscular and Electrodiagnostic Medicine (AANEM) and the American Academy of Neurology (AAN), through a cooperative agreeCorrespondence to: J.D. England; e-mail: [email protected] C 2014 Wiley Periodicals, Inc. V
Published online 13 September 2014 in (wileyonlinelibrary.com). DOI 10.1002/mus.24459
Editorial
Wiley
Online
Library
ment award with the Centers for Disease Control and Prevention, are publishing a series of evidence-based guidelines on the muscular dystrophies. The first in the series focuses on the LGMDs.4 As expected from the complexity of the topic, the complete guideline is detailed and long. The authors of this guideline reviewed and classified 699 full articles before arriving at conclusions and recommendations. Thus, the entire document is more like an encyclopedia of the LGMDs. Recognizing that hardly anyone will want to read the entire guideline word-for-word, the authors have provided a succinct and useful executive summary, which is published in Neurology. The full guideline is available as a data supplement and appendices on the Neurology Web site (www.neurology.org). My advice is to read the executive summary in full and to access the supplementary data for more information. Notably useful sections within the supplementary material are the figures, which contain algorithms to help clinicians narrow the differential diagnosis of LGMD based upon the pattern of weakness, the inheritance pattern, and the presence of distinguishing clinical and muscle biopsy findings. Following these recommendations should help clinicians select the most appropriate genetic testing and treatment for the individual patient. Although not part of the guideline, an additional free online resource, which is helpful in refining the subtype diagnosis for LGMDs, is provided by the Jain Foundation (www.jain-foundation.org). This site provides an automated LGMD diagnosis assistant which predicts the most likely type(s) of LGMD based on clinical and laboratory findings. Using Bayesian analysis, the tool determines predicted probabilities and concordance scores for the subtypes of LGMD for individual patients. I suggest using it as a complement to the algorithms in the LGMD guideline. As for the future, guidelines on the congenital muscular dystrophies, facioscapulohumeral dystrophy, and the myotonic dystrophies are also in the pipeline for publication. Please stay tuned. MUSCLE & NERVE
November 2014
721
REFERENCES 1. Walton JN, Nattrass FJ. On the classification, natural history and treatment of the myopathies. Brain 1954;77:169–231. 2. Bushby KM. Diagnostic criteria for the limb-girdle muscular dystrophies: report of the ENMC Consortium on Limb-Girdle Dystrophies. Neuromuscul Disord 1995;5:71–74.
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3. Bushby KM, Beckmann JS. The limb-girdle muscular dystrophies – proposal for a new nomenclature. Neuromuscul Disord 1995;5:337–343. 4. Narayanaswami P, Weiss M, Selcen D, David W, Raynor E, Carter G, et al. Evidence-based guideline summary: diagnosis and treatment of limb-girdle and distal dystrophies: 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 2014.
MUSCLE & NERVE
November 2014
Muscle Nerve 50: 721–722, 2014
MAKING SENSE OF THE MUSCULAR DYSTROPHIES: DIAGNOSIS AND TREATMENT GUIDELINE FOR LIMB-GIRDLE MUSCULAR DYSTROPHY JOHN D. ENGLAND, MD Department of Neurology, School of Medicine, Louisiana State University Health Sciences Center, 1542 Tulane Avenue, New Orleans, Louisiana, 70112, USA
The limb-girdle muscular dystrophies (LGMDs) are a heterogeneous group of genetically determined myopathies. In 1954, Walton and Nattrass proposed LGMD as a distinct clinical phenotype to differentiate it from the 3 most common muscular dystrophies (myotonic, Duchenne, and facioscapulohumeral).1 For the most part, the clinical phenotype of predominantly proximal muscle weakness involving pelvic and shoulder girdle muscles remains valid, but genetic diagnosis has widened the clinical phenotype to include other patterns of weakness. For instance, some patients have predominantly distal or even scapuloperoneal patterns of weakness. Diagnosis of LGMD now rests upon genetic analysis, and this has demonstrated that LGMD can exhibit striking phenotypic and genetic variability. The current nomenclature, which was established in 1995, divides LGMD into autosomal dominant (LGMD1) and autosomal recessive (LGMD2) types.2,3 Additional subtypes are designated by an alphabetical lettering system (e.g., LGMD1A, LGMD1B, etc.), which is based upon the order of discovery for each genetic subtype. At this time, there are 8 well-defined autosomal dominant (LGMD1A-1H) and 19 well-defined autosomal recessive (LGMD2A-2S) subtypes. Undoubtedly, more will be described. Although the most prevalent subtypes are LGMD2A (calpain-3), LGMD2B (dysferlin), LGMD2C-2F (sarcoglycans), and LGMD2I (fukutin-related protein), the complexity of the LGMDs has become rather staggering. Even for most neuromuscular experts, keeping current in the field is difficult. Because of the importance and complexity of the muscular dystrophies, the American Association of Neuromuscular and Electrodiagnostic Medicine (AANEM) and the American Academy of Neurology (AAN), through a cooperative agreeCorrespondence to: J.D. England; e-mail: [email protected] C 2014 Wiley Periodicals, Inc. V
Published online 13 September 2014 in (wileyonlinelibrary.com). DOI 10.1002/mus.24459
Editorial
Wiley
Online
Library
ment award with the Centers for Disease Control and Prevention, are publishing a series of evidence-based guidelines on the muscular dystrophies. The first in the series focuses on the LGMDs.4 As expected from the complexity of the topic, the complete guideline is detailed and long. The authors of this guideline reviewed and classified 699 full articles before arriving at conclusions and recommendations. Thus, the entire document is more like an encyclopedia of the LGMDs. Recognizing that hardly anyone will want to read the entire guideline word-for-word, the authors have provided a succinct and useful executive summary, which is published in Neurology. The full guideline is available as a data supplement and appendices on the Neurology Web site (www.neurology.org). My advice is to read the executive summary in full and to access the supplementary data for more information. Notably useful sections within the supplementary material are the figures, which contain algorithms to help clinicians narrow the differential diagnosis of LGMD based upon the pattern of weakness, the inheritance pattern, and the presence of distinguishing clinical and muscle biopsy findings. Following these recommendations should help clinicians select the most appropriate genetic testing and treatment for the individual patient. Although not part of the guideline, an additional free online resource, which is helpful in refining the subtype diagnosis for LGMDs, is provided by the Jain Foundation (www.jain-foundation.org). This site provides an automated LGMD diagnosis assistant which predicts the most likely type(s) of LGMD based on clinical and laboratory findings. Using Bayesian analysis, the tool determines predicted probabilities and concordance scores for the subtypes of LGMD for individual patients. I suggest using it as a complement to the algorithms in the LGMD guideline. As for the future, guidelines on the congenital muscular dystrophies, facioscapulohumeral dystrophy, and the myotonic dystrophies are also in the pipeline for publication. Please stay tuned. MUSCLE & NERVE
November 2014
721
REFERENCES 1. Walton JN, Nattrass FJ. On the classification, natural history and treatment of the myopathies. Brain 1954;77:169–231. 2. Bushby KM. Diagnostic criteria for the limb-girdle muscular dystrophies: report of the ENMC Consortium on Limb-Girdle Dystrophies. Neuromuscul Disord 1995;5:71–74.
722
Editorial
3. Bushby KM, Beckmann JS. The limb-girdle muscular dystrophies – proposal for a new nomenclature. Neuromuscul Disord 1995;5:337–343. 4. Narayanaswami P, Weiss M, Selcen D, David W, Raynor E, Carter G, et al. Evidence-based guideline summary: diagnosis and treatment of limb-girdle and distal dystrophies: 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 2014.
MUSCLE & NERVE
November 2014
