title: Diagnostic approach to the congenital muscular dystrophies.
abstract: Congenital muscular dystrophies (CMDs) are early onset disorders of muscle with histological features suggesting a dystrophic process. The congenital muscular dystrophies as a group encompass great clinical and genetic heterogeneity so that achieving an accurate genetic diagnosis has become increasingly challenging, even in the age of next generation sequencing. In this document we review the diagnostic features, differential diagnostic considerations and available diagnostic tools for the various CMD subtypes and provide a systematic guide to the use of these resources for achieving an accurate molecular diagnosis. An International Committee on the Standard of Care for Congenital Muscular Dystrophies composed of experts on various aspects relevant to the CMDs performed a review of the available literature as well as of the unpublished expertise represented by the members of the committee and their contacts. This process was refined by two rounds of online surveys and followed by a three-day meeting at which the conclusions were presented and further refined. The combined consensus summarized in this document allows the physician to recognize the presence of a CMD in a child with weakness based on history, clinical examination, muscle biopsy results, and imaging. It will be helpful in suspecting a specific CMD subtype in order to prioritize testing to arrive at a final genetic diagnosis.
authors.affiliation: National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States. Electronic address: carsten.bonnemann@nih.gov.
authors.forename: Carsten G
authors.initials: CG
authors.lastname: Bönnemann
authors.affiliation: Driscoll Children's Hospital, Corpus Christi, TX, United States.
authors.forename: Ching H
authors.initials: CH
authors.lastname: Wang
authors.affiliation: Hôpital Raymond Poincaré, Garches, and UFR des sciences de la santé Simone Veil (UVSQ), France.
authors.forename: Susana
authors.initials: S
authors.lastname: Quijano-Roy
authors.affiliation: Hôpital Universitaire des Enfants Reine Fabiola, Brussels and Ghent University Hospital, Ghent, Belgium.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Deconinck
authors.affiliation: Bambino Gesu' Children's Research Hospital, Rome, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Bertini
authors.affiliation: UMR787 INSERM/UPMC and Reference Center for Neuromuscular Disorders, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
authors.forename: Ana
authors.initials: A
authors.lastname: Ferreiro
authors.affiliation: Dubowitz Neuromuscular Centre, UCL Institute of Child Health, London, United Kingdom.
authors.forename: Francesco
authors.initials: F
authors.lastname: Muntoni
authors.affiliation: Dubowitz Neuromuscular Centre, UCL Institute of Child Health, London, United Kingdom.
authors.forename: Caroline
authors.initials: C
authors.lastname: Sewry
authors.affiliation: INSERM U827, Laboratoire de Génétique Moleculaire, Montpellier, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Béroud
authors.affiliation: University of Iowa, Iowa City, IA, United States.
authors.forename: Katherine D
authors.initials: KD
authors.lastname: Mathews
authors.affiliation: University of Iowa, Iowa City, IA, United States.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Moore
authors.affiliation: Stanford University School of Medicine, Stanford, CA, United States.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Bellini
authors.affiliation: Kaiser SCPMB, Los Angeles, CA, United States.
authors.forename: Anne
authors.initials: A
authors.lastname: Rutkowski
authors.affiliation: Murdoch Childrens Research Institute, Melbourne, Victoria, Australia.
authors.forename: Kathryn N
authors.initials: KN
authors.lastname: North
mesh_terms: D001921:Brain / Q000473:pathology / Q000503:physiopathology; D002648:Child; D032921:Consensus; D003937:Diagnosis, Differential; D006801:Humans; D007223:Infant; D007866:Leg / Q000473:pathology / Q000503:physiopathology; D008279:Magnetic Resonance Imaging; D009136:Muscular Dystrophies / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology
keywords: Alpha-dystroglycan; Collagen VI; Congenital muscular dystrophy; Diagnostic guideline; Lamin A/C; Laminin alpha2; RYR1; SEPN1