We searched Medline, Embase, Web of Science, and the Cochrane Library databases for peer-reviewed English-language articles published from Jan 1, 2006, to Sept 30, 2013, for the eight original topics and from Jan 1, 1990, to Sept 30, 2013, for the three new topics. The literature was searched using the key search terms “Duchenne” or “muscular dystrophy,” or both, paired with one of 626 search terms (appendix). The literature search identified 1215 articles after duplicates were removed.
ReviewDiagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and neuromuscular, rehabilitation, endocrine, and gastrointestinal and nutritional management
Introduction
Duchenne muscular dystrophy (DMD) is a lethal X-linked recessive neuromuscular disorder caused by mutations in the dystrophin gene that result in absent or insufficient functional dystrophin, a cytoskeletal protein that enables the strength, stability, and functionality of myofibres. Prevalence of DMD has been reported as 15·9 cases per 100 000 live male births in the USA and 19·5 cases per 100 000 live male births in the UK.1, 2, 3 Progressive muscular damage and degeneration occurs in people with DMD, resulting in muscular weakness, associated motor delays, loss of ambulation, respiratory impairment, and cardiomyopathy. Although the clinical course of skeletal muscle and cardiac involvement can be variable, death usually occurs as a result of cardiac or respiratory compromise.4, 5 This is part 1 of a three-part update of the 2010 DMD care considerations,6, 7, 8 which has been supported by the US Centers for Disease Control and Prevention (CDC) with involvement of the TREAT-NMD network for neuromuscular diseases, the Muscular Dystrophy Association, and Parent Project Muscular Dystrophy.
The decision to update the care considerations was driven by several important developments. First, with multidisciplinary care, the survival of patients with DMD has improved, and the diagnostic and therapeutic approach of the relevant subspecialties is evolving.9, 10, 11, 12 With more widespread realisation of prolonged survival, multiple subspecialties have shifted to more anticipatory diagnostic and therapeutic strategies, to achieve prevention, early identification, and treatment of predictable and potentially modifiable disease complications. Second, accompanying the expectation of longer survival is an increasing emphasis on quality of life and psychosocial management. Moreover, an urgent need now exists to coordinate and improve patient transitions from childhood to adulthood. Third, this update was necessitated by the growing experience with existing therapies and the anticipation of emerging genetic and molecular therapies for DMD.13 Specifically, new information is available on the efficacy, side-effects, and limitations of glucocorticoids,14, 15 and clinically meaningful and reliable biomarkers and outcome measures need to be identified to assess emerging therapies.
In part 1 of this Review, we cover the following topics: diagnosis, neuromuscular management, rehabilitation management, endocrine management (including growth, puberty, and adrenal insufficiency), and gastrointestinal management (including nutrition and dysphagia). Parts 2 and 3 of this Review describe the care considerations for other topic areas, including an expanded section on psychosocial management and new sections on primary care, emergency management, and transitions of care across the lifespan. Figure 1 provides an overview of assessments and interventions across all topics, organised by stage of disease.
Section snippets
Methods
In 2014, based on their clinical perspectives and expertise, the DMD Care Considerations Working Group (CCWG) steering committee identified 11 topics to be included in this update of the 2010 DMD care considerations.6 Eight of the topics were addressed in the original care considerations: (1) diagnosis, (2) neuromuscular management, (3) rehabilitation management, (4) gastrointestinal and nutritional management, (5) respiratory management, (6) cardiac management, (7) orthopaedic and surgical
Diagnosis
Achieving a timely and accurate diagnosis of DMD is a crucial aspect of care. The method for diagnosing DMD has not changed significantly since 2010 (figure 2).6 The diagnostic process typically begins in early childhood after suggestive signs and symptoms are noticed, such as weakness, clumsiness, a Gowers' sign, difficulty with stair climbing, or toe walking. Prompt referral to a neuromuscular specialist, with input from a geneticist or genetic counsellor, can avoid diagnostic delay.18 Less
Neuromuscular management
After diagnosis, the neuromuscular specialist will serve as the lead clinician, taking overall responsibility for care of the person with DMD and performing multiple roles and responsibilities across the individual's lifetime (panel 1). The neuromuscular specialist is uniquely qualified to guide patients and their families through the increasingly complex and technological diagnostic and therapeutic landscape of contemporary DMD care.
Rehabilitation management
DMD is characterised by well known patterns of progressive muscle degeneration and weakness, postural compensations, risk of progressive contracture and deformity, and functional losses resulting from dystrophin deficiency.6, 7 Improved DMD management has resulted in prolongation of ambulation,47 decreased prevalence of severe contracture and deformity, including scoliosis,37 and prolonged function and participation in all areas of life.47, 48 Rehabilitation personnel include physicians,
Endocrine management
The endocrine complications of DMD and its treatment include impaired growth, delayed puberty, and adrenal insufficiency. The goals of endocrine care are to monitor growth and development, identify and diagnose hormone deficiencies, provide endocrine hormone replacement therapy when indicated, and prevent a life-threatening adrenal crisis. A few relevant expert-opinion papers and reviews have been published,94, 95, 96 but data are scarce on the safety and efficacy of growth hormone and
Gastrointestinal and nutritional management
Individuals with DMD often have gastrointestinal or nutritional complications, including weight gain or loss, dietary or nutrient imbalance, fluid imbalance, low bone density, swallowing dysfunction, and mandibular contracture.106 Contributing factors include glucocorticoid treatment, decreased energy expenditure, and immobility.107 These nutritional imbalances can negatively affect the respiratory, skeletal muscle, and cardiac systems.
The aim of nutritional care is to prevent overweight or
Conclusions and future directions
In part 1 of this three-part update of the DMD care considerations, we have presented guidance on diagnosis, and neuromuscular, rehabilitation, endocrine, and gastrointestinal management. Highlights of the new care considerations include guidance on the care of female carriers of DMD; an overview of new molecular and genetic therapies; advances in rehabilitation assessments and the emergence of more advanced, technologically enabled rehabilitation therapies; new guidance on endocrine problems,
Search strategy and selection criteria
References (129)
- et al.
Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and pharmacological and psychosocial management
Lancet Neurol
(2010) - et al.
Diagnosis and management of Duchenne muscular dystrophy, part 2: implementation of multidisciplinary care
Lancet Neurol
(2010) - et al.
Study of Duchenne muscular dystrophy long-term survivors aged 40 years and older living in specialized institutions in Japan
Neuromuscul Disord
(2017) - et al.
Developing standardized corticosteroid treatment for Duchenne muscular dystrophy
Contemp Clin Trials
(2017) - et al.
Delayed diagnosis in Duchenne muscular dystrophy: data from the Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet)
J Pediatr
(2009) - et al.
Motor and cognitive delay in Duchenne muscular dystrophy: implication for early diagnosis
J Pediatr
(2014) - et al.
195th ENMC International Workshop: Newborn screening for Duchenne muscular dystrophy 14-16th December, 2012, Naarden, The Netherlands
Neuromuscul Disord
(2013) - et al.
Corticosteroid treatment and growth patterns in ambulatory males with Duchenne muscular dystrophy
J Pediatr
(2016) - et al.
Ataluren in patients with nonsense mutation Duchenne muscular dystrophy (ACT DMD): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial
Lancet
(2017) - et al.
Pharmacological advances for treatment in Duchenne muscular dystrophy
Curr Opin Pharmacol
(2017)
Motor and cognitive assessment of infants and young boys with Duchenne muscular dystrophy: results from the Muscular Dystrophy Association DMD Clinical Research Network
Neuromuscul Disord
Suitability of North Star Ambulatory Assessment in young boys with Duchenne muscular dystrophy
Neuromuscul Disord
The performance of the upper limb scores correlate with pulmonary function test measures and Egen Klassifikation scores in Duchenne muscular dystrophy
Neuromuscul Disord
Continuous monitoring and quantification of multiple parameters of daily physical activity in ambulatory Duchenne muscular dystrophy patients
Eur J Paediatr Neurol
Reliability of the Performance of Upper Limb assessment in Duchenne muscular dystrophy
Neuromuscul Disord
Prevalence of fatigue, pain, and affective disorders in adults with Duchenne muscular dystrophy and their associations with quality of life
Arch Phys Med Rehabil
Ambulatory capacity and disease progression as measured by the 6-minute-walk-distance in Duchenne muscular dystrophy subjects on daily corticosteroids
Neuromuscul Disord
One year outcome of boys with Duchenne muscular dystrophy using the Bayley-III scales of infant and toddler development
Pediatr Neurol
Hip kinetics during gait are clinically meaningful outcomes in young boys with Duchenne muscular dystrophy
Gait Posture
Attention deficit hyperactivity disorder and cognitive function in Duchenne muscular dystrophy: phenotype-genotype correlation
J Pediatr
Behavior patterns in Duchenne muscular dystrophy: report on the Parent Project Muscular Dystrophy behavior workshop 8–9 of December 2006, Philadelphia, USA
Neuromuscul Disord
Combination of steroids and ischial weight-bearing knee ankle foot orthoses in Duchenne's muscular dystrophy prolongs ambulation past 20 years of age—a case report
Neuromuscul Disord
Knee-ankle-foot orthosis in children with Duchenne muscular dystrophy: user views and adjustment
Eur J Paediatr Neurol
Exercise in neuromuscular diseases
Phys Med Rehabil Clin N Am
Endocrine aspects of Duchenne muscular dystrophy
Neuromuscul Disord
Report on the Second Endocrine Aspects Of Duchenne Muscular Dystrophy Conference December 1–2, 2010, Baltimore, Maryland, USA
Neuromuscul Disord
Patterns of growth in ambulatory males with Duchenne muscular dystrophy
J Pediatr
Growth hormone treatment in boys with Duchenne muscular dystrophy and glucocorticoid-induced growth failure
Neuromuscul Disord
The burden, epidemiology, costs and treatment for Duchenne muscular dystrophy: an evidence review
Orphanet J Rare Dis
Evidence-based path to newborn screening for Duchenne muscular dystrophy
Ann Neurol
Newborn bloodspot screening for Duchenne muscular dystrophy: 21 years experience in Wales (UK)
Eur J Hum Genet
Advances in genetic therapeutic strategies for Duchenne muscular dystrophy
Exp Physiol
State of the art advances in Duchenne muscular dystrophy
EMJ
Family guide in different languages
Contemporary cardiac issues in Duchenne muscular dystrophy. Working Group of the National Heart, Lung, and Blood Institute in collaboration with Parent Project Muscular Dystrophy
Circulation
The respiratory management of patients with Duchenne muscular dystrophy: a DMD care considerations working group specialty article
Pediatr Pulmonol
Improvement of survival in Duchenne muscular dystrophy: retrospective analysis of 835 patients
Acta Myol
Recent advances in innovative therapeutic approaches for Duchenne muscular dystrophy: from discovery to clinical trials
Am J Transl Res
Efficacy and safety of deflazacort vs prednisone and placebo for Duchenne muscular dystrophy
Neurology
Practice guideline update summary: Corticosteroid treatment of Duchenne muscular dystrophy: Report of the Guideline Development Subcommittee of the American Academy of Neurology
Neurology
The RAND/UCLA Appropriateness Method user's manual
Improved detection of deletions and duplications in the DMD gene using the multiplex ligation-dependent probe amplification (MLPA) method
Biochem Genet
Microarray-based mutation detection in the dystrophin gene
Hum Mutat
A comprehensive genomic approach for neuromuscular diseases gives a high diagnostic yield
Ann Neurol
Whole dystrophin gene analysis by next-generation sequencing: a comprehensive genetic diagnosis of Duchenne and Becker muscular dystrophy
Mol Genet Genomics
Targeted next-generation sequencing as a comprehensive test for patients with and female carriers of DMD/BMD: a multi-population diagnostic study
Eur J Hum Genet
Genetic diagnosis of Duchenne/Becker muscular dystrophy using next-generation sequencing: validation analysis of DMD mutations
J Hum Genet
Opinion 2.138—genetic testing of children
Screening for Duchenne muscular dystrophy
Arch Dis Child
Newborn screening: toward a uniform screening panel and system
Genet Med
Cited by (710)
The unconditioned fear response in vertebrates deficient in dystrophin
2024, Progress in NeurobiologyNew therapeutic avenues for Duchenne muscular dystrophy
2024, The Lancet Neurology
- †
Members listed at the end of the paper