Nevada Medical Home Portal - Duchenne & Becker Muscular Dystrophies

Duchenne & Becker Muscular Dystrophies

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Key Points
Practice Guidelines
Diagnosis
Prognosis
Treatment & Management
Services & Referrals
ICD-10 Coding
Resources

Guidance for primary care clinicians diagnosing and managing children with Duchenne and Becker dystrophies

Guidance for primary care clinicians diagnosing and managing children with Duchenne or Becker muscular dystrophy Dystrophinopathies, including Duchenne (DMD) and Becker (BMD) muscular dystrophies, represent varying clinical presentations of an X-linked, progressive symmetric muscle weakness caused by a relative or absolute absence of dystrophin. Weakness is predominantly proximal, but progression eventually involves distal muscles. Muscles are gradually replaced by fatty, fibrotic connective tissue. DMD is the most common and most severe form of the disease, with a prevalence of about 1:3500 male births. Dystrophinopathies occur primarily in males; however, female carriers can occasionally manifest symptoms and are increasingly recognized. Symptoms are variable and can include cardiac and motor issues, especially later in adulthood.

Other Names

Dystrophinopathy
Pseudohypertrophic muscular dystrophy

Key Points

Creatine kinase (CK) test for any child with unexplained motor delays or muscle weakness
With an increasing number of approved therapies, earlier diagnosis becomes increasingly important. CK levels in DMD are markedly elevated in all DMD patients, even at very young ages with minimal symptoms, so early diagnosis can be obtained for a very low cost based on screening CK. Yet, many patients are not identified until age 8 or 9, or even older, despite the typical age of onset of weakness. To ensure early identification of children with DMD, a CK should be obtained in any child presenting with unexplained motor delays and any evidence of muscle weakness.

Negative genetic testing despite clinical presentation
Genetic testing laboratories can detect mutations in the DMD gene in up to 98% of patients after stepwise testing, including deletion/duplication tests followed by sequencing the full DMD gene. Dystrophinopathies (GeneReviews)A muscle biopsy with dystrophin staining should be recommended when the clinical presentation is consistent with DMD but genetic testing is negative. Even with the best available technology, some genetic diagnoses remain elusive due to genetic anomalies that are difficult to detect under routine testing paradigms. In these cases, the absence of dystrophin staining on muscle biopsy confirms the diagnosis. Additional testing may be available in some centers on a research basis, including RNA sequencing from a muscle biopsy specimen that can identify the genetic mutation in most cases.

Steps before starting steroids
Before starting steroids, ensure all immunizations are current, especially pneumococcus. Also, ensure immunity to chickenpox and test for tuberculosis if warranted. While taking steroids, annual influenza shots should be an injectable, killed-virus type rather than a live virus.

Practice Guidelines

Standard of care guidelines were first published in 2010 and updated in 2018 to include new recommendations on the transition from pediatric to adult care, endocrine management, primary care, and emergency management. No practice guidelines have been published. Guidance based on expert opinion includes:

Birnkrant DJ, Bushby K, Bann CM, Apkon SD, Blackwell A, Brumbaugh D, Case LE, Clemens PR, Hadjiyannakis S, Pandya S, Street N, Tomezsko J, Wagner KR, Ward LM, Weber DR.
Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and neuromuscular, rehabilitation, endocrine, and gastrointestinal and nutritional management.
Lancet Neurol. 2018;17(3):251-267. PubMed abstract / Full Text

Birnkrant DJ, Bushby K, Bann CM, Alman BA, Apkon SD, Blackwell A, Case LE, Cripe L, Hadjiyannakis S, Olson AK, Sheehan DW, Bolen J, Weber DR, Ward LM.
Diagnosis and management of Duchenne muscular dystrophy, part 2: respiratory, cardiac, bone health, and orthopaedic management.
Lancet Neurol. 2018;17(4):347-361. PubMed abstract / Full Text

Birnkrant DJ, Bushby K, Bann CM, Apkon SD, Blackwell A, Colvin MK, Cripe L, Herron AR, Kennedy A, Kinnett K, Naprawa J, Noritz G, Poysky J, Street N, Trout CJ, Weber DR, Ward LM.
Diagnosis and management of Duchenne muscular dystrophy, part 3: primary care, emergency management, psychosocial care, and transitions of care across the lifespan.
Lancet Neurol. 2018;17(5):445-455. PubMed abstract / Full Text

Diagnosis

Presentations

Boys with DMD typically present in the preschool years with proximal muscle weakness, manifesting as frequent falls, difficulty getting up from the floor, a waddling, wide-based lordotic gait, toe-walking, and large calves. A positive Gower sign may be present.

The mean age of diagnosis of DMD without a family history is 4-5 years, with many patients not identified until age 8 or 9, or even older. Symptoms are often identifiable by age 2, but diagnosis is delayed an average of 2.5 years. [Ciafaloni: 2009] With the increasing amount of approved therapies, earlier diagnosis becomes that much more important. To ensure early identification of children with DMD, a CK should be obtained in any child presenting with unexplained motor delays and any evidence of muscle weakness. CK levels in DMD are markedly elevated, often over 10,000, in all DMD patients, even at very young ages with minimal symptoms. So, early diagnosis can be obtained for a very low cost based on screening CK.

Muscle weakness worsens over time, resulting in loss of ambulation by 8-13 years of age. Orthopedic manifestations of DMD, such as toe-walking, scoliosis, and contractures of the ankles, knees, and hips, are common. Bowel and bladder function are often mildly affected with symptoms of constipation and urinary urgency. Mild to moderate developmental delay is common but not universal. Treatment with oral corticosteroids (prednisone or deflazacort) can delay loss of ambulation by several years and is now considered standard of care despite side effects. After loss of ambulation, muscle weakness continues to progress, and respiratory weakness leads to difficulty breathing.

For an excellent review of presenting symptoms in patients with neuromuscular disease, including photographs and video of boys with DMD demonstrating hypertrophied calf muscles, gait abnormalities, and the Gowers' sign, see Muscle Weakness Video Library (childmuscleweakness.org).

Boys with BMD may present later but with a similar distribution of weakness in proximal muscles, particularly the hip girdle muscles. Progression is slower, and walking continues into the late teens, sometimes into the thirties or more. Neck flexion strength in individuals with BMD is often preserved.

Rarely, females with 1 normal gene and 1 altered DMD gene may have muscle weakness, cramping, high creatine kinase, and cardiomyopathy symptoms. Symptoms in these “manifesting carriers” are thought to be due to the nonrandom inactivation of one of the X chromosomes (by the Lyon Hypothesis). [Soltanzadeh: 2010] In the early embryo stage of females, one X chromosome is inactivated in each cell, resulting in half of the embryo's X chromosomes being from the mother and half from the father. Occasionally, there is disproportionate inactivation of the X chromosomes from one parent. When this happens to the normal X chromosomes in a DMD carrier, sufficient reduction in dystrophin production results in symptoms. Cardiomyopathy is the most important carrier phenotype, and all carrier females should be screened by cardiac imaging and EKG at least every 5 years.

Diagnostic Criteria & Classifications

DMD and BMD may be diagnosed based on typical clinical presentation, lack of or decrease in dystrophin staining on a muscle biopsy, and/or the demonstration of a mutation in the DMD gene.

Screening & Diagnostic Testing

Newborn screening for DMD is emerging in research-based programs. The screening protocol starts with the measurement of CK levels from the dried blood spot with secondary genetic testing for mutations of the DMD gene. An application for the inclusion of DMD on the Recommended Uniform Screening Panel was submitted in 2022.

Screening Family Members

The mothers of boys with DMD/BMD may also be at risk for cardiac problems. They should be evaluated by genetic testing to confirm carrier status and, if positive, evaluation and monitoring by a cardiologist.

Laboratory Testing

A very elevated creatine kinase (CK) is always present but is not specific to DMD. CK values from boys with DMD are in the thousands (20,000 or higher is not unusual). A CK is useful for diagnosis only; its level is not followed once the diagnosis is established. The degree of elevation is not significant at diagnosis; for instance, a value of 20,000 in a patient does not indicate a more severe form of DMD than a value of 12,000 in another patient. Transaminases commonly screened for liver dysfunction (AST and ALT) are almost always abnormally high. These enzymes are present in the muscle, and elevation reflects leaky muscle fiber membranes rather than liver disease (unless other signs of liver disease, such as jaundice or coagulopathy, are also present). Importantly, elevated transaminases sometimes bring a child to the attention of a gastroenterologist before muscle disease is diagnosed. If so, measurement of the liver-specific enzyme, gamma-glutamyl transferase (GGT), should be normal, as should bilirubin and alkaline phosphatase measures. Before extensive testing for liver disease, CK should be checked early in any child with elevated transaminases. Another important laboratory finding in boys with DMD is low creatinine. Low creatinine reflects low muscle mass. Renal problems are not common in boys with DMD, but if concerned for renal function, other markers of renal function, such as cystatin C should be obtained.

CK elevated but not as profoundly elevated in boys with BMD. In boys with advanced DMD, the CK can normalize due to very low muscle mass.

Genetic Testing

Molecular genetic testing should be performed to confirm the diagnosis and guide genetic counseling for family members. The type of mutation may determine the boy's eligibility for treatment (exon skipping therapy for exon 45, 51, or 53) or clinical trials, e.g., nonsense readthrough, exon skipping, and gene replacement therapies now in clinical trials. See Research in DMD (Parent Project Muscular Dystrophy). Because not all mutations can be identified, a negative genetic test does not rule out DMD. Standard testing includes stepwise deletion/duplication testing followed by sequencing of the full DMD gene, which detects the mutation in >95% of the cases. See Genetic Testing Labs - Dystrophinopathies (GeneTests) for the most comprehensive genetic testing. If the genetic testing is negative, but the clinical situation is highly suggestive of DMD, a muscle biopsy is recommended to confirm the absence of dystrophin. Some centers offer RNA-sequencing from muscle samples in these cases, which can usually identify the causative mutation.

Other Testing

Muscle biopsy was common before genetic testing became widely available. It is not widely performed for DMD but may be useful with negative genetic testing. In addition to non-specific signs of muscular dystrophy, including muscle fiber degeneration and regeneration, central nuclei, and replacement of muscle fibers by fat and connective tissue, dystrophin staining will be 0-5% in boys with DMD and 20-50% in boys with BMD. [Darras: 2008]

Genetics & Inheritance

DMD and BMD are X-linked and caused by mutations in the DMD gene, which codes for the dystrophin protein. The DMD gene is the largest in the human genome. Deletions and duplications of 1 or more exons are common and account for 70-80% of mutations. Some areas of the gene are more prone to mutation than others, with most patients having deletions between exons 44-55. Mutations that maintain an open reading frame are usually associated with BMD, while mutations that disrupt the reading frame result in DMD, but there are well-known exceptions. Out-of-frame deletions, exons 3-7 or exon 44, for example, are known to have variably milder phenotypes. [Flanigan: 2009]While genetic, DMD and BMD are not always inherited – 1/3 of cases are new mutations (de novo) in the boy, 1/3 are new in the mother, and 1/3 are inherited from deeper in the pedigree. Mothers of boys with DMD who have a known mutation, and female siblings over age 18, should be screened for carrier status and counseled accordingly. Symptomatic cardiomyopathy and mild motor symptoms are increasingly recognized in carrier females; screen for cardiomyopathy with a baseline echocardiogram in adolescence, then every 5 years starting at 25-30 years of age. Approximately 9-14% of mothers who are carriers may be missed by standard genetic testing because of germline mosaicism, where the maternal germ cells carry the mutation, but somatic cells (including blood cells) do not. [Helderman-van: 2009] Mothers testing negative for carrier status should be counseled about this possibility.

Prenatal diagnosis and preimplantation testing are available when the mutation in the DMD gene has been identified in the family. With the high cost of newly approved medications, some insurers have approved coverage of preimplantation testing.

Prevalence

Prevalence varies widely according to the method of ascertainment. Point prevalence of DMD has been reported as 1:9000 in Canada [Mah: 2014] and 1:9800 based on CDC data from 6 US states. [Romitti: 2015] Worldwide prevalence estimates of Duchenne and Becker muscular dystrophies vary, likely due to differences in diagnostic criteria, ascertainment, and survival. No population-based prevalence data for DMD and BMD by race/ethnicity have been published in the United States. [Romitti: 2015]

Differential Diagnosis

Given the relatively high prevalence of DMD among neuromuscular disorders, a diagnosis of DMD is highly likely in typical clinical scenarios (4- to 5-year-old boy with an unusual gait, Gowers' sign, and a marked elevation in CK). Still, other neuromuscular disorders should be considered. Before genetic testing and/or dystrophin protein staining on biopsy were available, DMD/BMD could be confused with spinal muscular atrophy (SMA), congenital myopathies, other muscular dystrophies (especially limb girdle muscular dystrophy), polymyositis, and other muscle diseases. Genetic diagnosis provides a definitive diagnosis in >95% of patients.

Differentiation between Duchenne and Becker muscular dystrophy may depend on the examiner's judgment, particularly before age 12. Some boys fit easily into a category: The boy who presents at age 2 and uses a wheelchair exclusively by age 10 has Duchenne, whereas the boy who presents at age 11 and is still walking at age 17 has Becker. But there are many in-between cases, and the nomenclature is less important than understanding that they all are due to a mutation in the DMD gene, and all will have progressive muscle weakness and, in many cases, respiratory and cardiac problems. Literature is increasingly evaluating the links between genotype and phenotype in these disorders.

Prognosis

Individuals with BMD often have a life expectancy into the 40s or later and can often walk into their 30s. Improved anticipatory care, including oral corticosteroid use, proactive care of heart and respiratory issues, early surgery for scoliosis, and early use of non-invasive ventilation, has enabled affected boys to walk and live longer. Susceptibility to respiratory infections and progressive deterioration of pulmonary function generally lead to death; however, with improved attention to respiratory care, cardiomyopathy with heart failure is becoming an increasingly important cause of mortality. Up to 50% of individuals with BMD die of cardiac complications. Cardiac death is less common in individuals with DMD (20%) but becoming more common as pulmonary complications are increasingly prevented and life expectancy is longer. [Darras: 2008]

Many new treatments are in development for DMD, including gene manipulation (exon skipping and nonsense readthrough) and gene replacement therapies. Many of these treatments, including the newly FDA-approved exon skipping therapies for patients with exon 45, 51, or 53 skip-amenable deletions, work only on specific mutations emphasizing the need for a confirmed genetic diagnosis. Dystrophinopathies (GeneReviews) and Muscular Dystrophy, Duchenne (OMIM)have more information. Increasingly, parent and provider groups are focusing on patient quality of life.

Treatment & Management

Boys with DMD should be followed by both primary care providers and Neuromuscular Clinics (see NV providers [2]). The primary care provider will continue routine well-child and acute-illness care, provide recommended hearing, vision, and behavioral health screening, follow developmental milestones, provide vaccinations, and coordinate care with a multi-disciplinary neuromuscular clinic. The Neuromuscular Clinic will provide Duchenne-related care and communicate with the boys’ primary care provider. If not available, the medical home will need to ensure proper surveillance.

Stages of muscular dystrophy
Based on available evidence and expert consensus, care guidelines for DMD can be found at Care Guidelines (Parent Project Muscular Dystrophy). These guidelines correlate to different disease stages, defined mostly by motor function, including diagnosis/early childhood, late ambulatory, early non-ambulatory, and late non-ambulatory stage. Each stage has somewhat different issues requiring surveillance and management. Transitions through these stages require different strategies.

Diagnosis/early childhood
Despite progressing weakness, patients in this stage retain relatively normal function in the community but can be slow in activities requiring significant physical exertion. As the child’s strength reaches a plateau phase, treatment with oral corticosteroids should be initiated. Corticosteroids lengthen the time before a wheelchair is needed and preserve lung and cardiac function. Risks and benefits should be discussed with the family. Problems with weight gain and behavior are most common. Parents should be warned about the potential for adrenal crisis (protocol) and never to stop steroids abruptly.

Nutrition should be discussed soon after diagnosis, as corticosteroids often cause weight gain. Vitamin D and calcium should be maximized since muscle weakness and treatment with corticosteroids may lead to bone fragility and fractures. Initial visits with cardiology and pulmonology should occur. Although these systems are unlikely to be significantly affected during this early phase. Boys with DMD may have features of autism, speech/language delay, learning problems, and/or intellectual impairment. These problems should be screened for at an early age and appropriate treatments started. DMD may cause joint problems, especially ankle stiffness, and a regimen of stretching, ankle foot orthotics, and nighttime stretching braces should be started as needed.

Late ambulatory
During the late ambulatory stage, boys are noticeably weaker, with an abnormal, waddling gait. They may need a wheelchair or scooter for longer distances. A handicapped placard may be helpful for the family, and school accommodations become increasingly important. Stretching exercises or braces should be continued. Cardiac and pulmonology evaluations should continue yearly. Learning and behavior should continue to be evaluated, and management put in place as necessary. Mental health issues such as anxiety or depression are common and may surface at this time.

Early non-ambulatory
During the early non-ambulatory stage, weakness continues progressing, including in the upper extremities. Scoliosis may develop and should be screened for on an ongoing basis with surgery as needed. Individuals will now be in power wheelchairs full-time. Additional special adaptive equipment may be needed. Many boys start having problems with cardiac and lung function, and regular visits with these specialists should continue. Mental health problems should be screened for and treated as necessary.

Late non-ambulatory
During the late non-ambulatory stage, emphasis should be placed on helping keep these young men healthy and independent as possible. Stretching of upper and lower extremities should be continued. Corticosteroids are continued depending on tolerability and side effects. Cardiac and pulmonology care should continue, and by this time, most patients are treated with non-invasive ventilation at night. Advanced schooling and jobs should be sought as possible. Mental health issues should be addressed. A transition to adult care usually occurs during this phase. Bone fragility and osteoporosis should be monitored and treated with bisphosphonate infusions as needed.

Neurology

Starting corticosteroids
Corticosteroids should be started in the Diagnosis/Early Ambulatory Stage. Long-term studies of boys with DMD show that corticosteroid treatment improves muscle strength and function, prolongs walking, and reduces long-term complications, particularly scoliosis. [Gloss: 2016] Evidence suggests that corticosteroids have a beneficial effect on respiratory and cardiac function. [Markham: 2008] [Bushby: 2005] [Schram: 2013]

Before starting corticosteroids, immunizations should be current and immunity to varicella and pneumococcus confirmed. Also, because steroid use in DMD is associated with an increased risk for osteoporosis, 25-OH vitamin D levels should be checked, and a referral made to a dietician to determine typical calcium and vitamin D intake. If necessary, recommend dietary Calcium and Vitamin D supplements.

Little evidence exists about the optimum time to start corticosteroid treatment or how long to continue it. Some investigators believe it should be started as early as possible; others believe that treatment should start around the age at which motor development starts to plateau (age 4-5 usually). [Manzur: 2008] [Merlini: 2003]

Prednisone is the most commonly used corticosteroid for DMD in the US, but deflazacort has been available in Europe and Canada for many years and is preferred in some countries. The recent approval of deflazacort by the FDA has made it available in the US, but the cost is high. Based on a recently published clinical trial, deflazacort is thought to have the same efficacy as prednisone, and daily administration of either steroid form is preferred to intermittent dosing. [Guglieri: 2022]

The recommended dosage of oral prednisone/prednisolone is 0.75 mg/kg/day (although doses as low as 0.3 mg/kg/day have some beneficial effects). The dose for deflazacort is 0.9 mg/kg/day. See [Houde: 2008]. Care guidelines recommend daily dosing; however, some experts prefer alternate regimens that may decrease side effects, particularly during the school week. Depending on the type/severity of emerging side effects with treatment, the clinician may decrease the prednisone dose from 0.75 to 0.5, or even 0.3 mg/kg/day and maintain some efficacy. Similar adjustments to deflazacort are common as well.

Potential side effects of corticosteroid treatment should be monitored closely and include:

Hypertension
Behavioral problems
Weight gain, with Cushingoid appearance and failure to gain expected height
Osteoporosis
Impaired immune and adrenal function
Impaired glucose tolerance
Gastrointestinal symptoms, including discomfort and gastric ulcers
Cataracts
Excessive hair growth
Acne and striae

Some side effects, such as weight gain and behavioral changes, can be managed without changing the dose. Other side effects, such as weight gain that does not respond to treatment, unacceptable behavior problems, high fasting/postprandial glucoses or diabetes, confirmed persistent hypertension, or severe GI complications, require dose reduction or stopping steroids.

Boys on corticosteroids should avoid frequent use of non-steroidal anti-inflammatory medications due to the increased risk of gastric irritation. Antacids, H2-blockers, or proton pump inhibitors may be used for stomach pain or heartburn. Calcium carbonate tablets may be doubly useful as a calcium supplement and as an antacid.

Stopping corticosteroids
Most studies supporting the use of corticosteroids in boys with DMD have centered on benefits in motor function and prolonged ambulation. There is little evidence to guide when and if corticosteroid treatment should be discontinued. Some experts continue to give steroids after boys with DMD become non-ambulatory since pulmonary and cardiac function may still benefit. [Balaban: 2005] In many cases, side effects, especially weight gain, begin to accumulate after the loss of ambulation. Patients and providers should carefully consider the risks and potential benefits of continuing corticosteroid use after the loss of ambulation. [Birnkrant: 2018] If the decision is made to discontinue, then the dose should be tapered over time and not stopped abruptly due to adrenal suppression and the risk of renal insufficiency.

Adrenal suppression
Chronic use of high-dose corticosteroids inhibits the function of the hypothalamic-pituitary-adrenal axis resulting in iatrogenic adrenal suppression. As a result, patients treated with long-term corticosteroids are at risk for adrenal insufficiency; this can occur even when the child looks Cushingoid due to the high-dose glucocorticoids. The glucocorticoids must not be stopped abruptly as this may result in adrenal crisis, especially in the setting of trauma, surgery, or major illness, which causes an increased physiologic need for endogenous corticosteroids. The exact dose of corticosteroids that causes suppression is not known; however, the higher the dose and longer the period of use, the more likely adrenal suppression occurs. A general rule of thumb in adults is more than 7.5 mg of prednisone a day, or the equivalent, places the individual at risk.

Stress dosing may be required if the boy becomes ill, suffers physiologic trauma, or needs surgery, potentially even minor surgery, because the trigger for adrenal insufficiency may be the anesthesia itself. Parents should be instructed about the risk and that they need to communicate with providers treating the patient.

If stress dosing is needed because of a surgery, trauma, or serious illness requiring hospitalization, stress dosing should be handled by the hospital physicians or anesthesiologist involved in the surgery. In cases of stress due to illness not requiring hospitalization, parents should know that the child may need treatment at home. Steroid Protocol for boys with DMD-Nicholoff (Parent Project MD) is a guide for providers in stress dosing.

Symptoms of adrenal insufficiency include hypotension, hyponatremia, hyperkalemia, nausea, abdominal pain, and/or hypoglycemia. [Bornstein: 2016] [Birnkrant: 2018] [Bowden: 2019] Stress dosing is usually achieved with hydrocortisone 50 mg/m2 per day and should be given to anyone taking less than the equivalent of physiologic dosing. For example, if a patient is on high-dose prednisone, they can continue their home dose but must get it preoperatively and perioperatively. Stress dosing needs to be given to anyone tapering off steroids and/or getting less than the equivalent of physiologic dosing at the time of surgery. This is roughly equivalent to 12 mg/m2 per day of prednisone or deflazacort.

Cardiology

Cardiac abnormalities are a significant cause of death and morbidity. The decreased activity of children in wheelchairs with end-stage disease can make cardiovascular symptoms less apparent. Cardiac exams are initially normal. With progression, signs of cardiac dysfunction, such as murmurs, irregular beats, and unusual heart sounds, may appear. The cardiac examination, however, may remain relatively normal even with advanced disease. Symptoms of weak cardiac muscle include shortness of breath and early fatigue.

The most common cardiac problem is dilated cardiomyopathy or an enlarged heart with poor cardiac output. The clinical course of cardiomyopathy – progressive decline in left ventricular function resulting in cardiac failure – is usually prolonged, though sudden death from arrhythmia may occur. Many patients do not show symptoms of cardiomyopathy due to their lack of physical activity, but early changes in cardiac function are usually apparent on cardiac imaging studies, e.g., echocardiogram or cardiac magnetic resonance imaging (MRI). Especially with advanced cardiomyopathy, arrhythmias are common, and periodic Holter monitoring should be considered. Thromboembolic events may occur in boys with significant cardiomyopathy, and anticoagulant therapy may be warranted.

When the echocardiogram (or MRI, which obtains more information than an ECHO, including the presence of fibrosis in the cardiac muscle) shows a deterioration of cardiac function, experts recommend starting an angiotensin-converting enzyme (ACE) inhibitor to limit further deterioration of cardiac function, even if the boy is not having any obvious problems. Patients with dilated cardiomyopathy often progress to heart failure, and cardiologists may add beta-blockers and diuretics. Advanced therapies such as left ventricular assist devices (LVADs) have been used in some cases. They may also be an option for boys with heart failure after careful consideration of risks and potential benefits.

Because changes in cardiac function are uncommon before the second decade of life, the Treat-NMD standards, [Birnkrant: 2018], recommend a cardiology evaluation with an echocardiogram and electrocardiogram (ECG) at the time of diagnosis every 2 years until age 10 and then annually unless progressive problems suggest the need for more frequent exams. [Feingold: 2017] Cardiology referral is also recommended before any major surgery. When present, clinical symptoms may include those associated with congestive heart failure (edema, shortness of breath, orthopnea), reduced cardiac output (especially fatigue), and/or arrhythmias. However, symptoms might be absent due to decreased skeletal muscle strength and decreased physical activity until very late in the course of the disease. With severe cardiomyopathy, thromboembolic events have been observed.

Early diagnosis and treatment of dilated cardiomyopathy, based on echocardiographic findings and not clinical deterioration, are advised. Initial medication options include angiotensin converting enzyme (ACE) inhibitors, such as enalapril or lisinopril, and angiotensin receptor blockers (ARBs), such as losartan. Some clinicians will start these medications at age 10, even before detection of reduced ejection fraction. The 2017 American Heart Association guidelines for the treatment of cardiac problems in children with neuromuscular disease include this approach as “may be considered.” [Feingold: 2017]

These medications are also commonly used to treat high blood pressure, which may be related to prolonged steroid exposure in boys with DMD. Other agents, such as beta-blockers, may be added in the setting of advanced dilated cardiomyopathy, depending on cardiology preference and disease manifestations. Other medications, such as diuretics, may be added when a patient has signs or symptoms of congestive heart failure.

Anti-arrhythmic therapy is sometimes needed as well. Left ventricular assist devices (LVADs) may be increasingly offered to boys in heart failure. In some cases, cardiac transplantation may be possible, although this varies with the site where the child is receiving care. Recent evidence suggests that prolonged steroid therapy may help delay the onset of cardiomyopathy. [Schram: 2013]

Respiratory

Boys with DMD usually die from complications related to the respiratory system, particularly respiratory failure during an infection. Symptoms of pneumonia should prompt evaluation by the Medical Home. Pneumovax and influenza vaccines should be kept up to date. Death from pneumonia/respiratory failure occurs in approximately 75% of older boys with DMD, often occurring within approximately one year of the appearance of daytime hypercapnia; this may be delayed with appropriate intervention. [Ishikawa: 1999] [Simonds: 1998] See [Birnkrant: 2010] for the newest respiratory guidelines for the care of children with DMD.
Early in the course of DMD, progressive muscle weakness leads to nocturnal hypoventilation and hypoxia, but the process is gradual and patients may not be aware of the problem. Begin monitoring for signs and symptoms of respiratory problems once the child is non-ambulatory. Inquire about symptoms of nighttime hypoventilation:

Morning headache
Daytime sleepiness
Increased restlessness during sleep, increased need for turning during sleep

Boys with DMD should be evaluated with pulmonary function testing and home oxygen saturation monitoring approximately every six months after they become non-ambulatory. Referral to a pediatric pulmonologist for management is recommended. Respiratory muscle weakness leads to weak coughing and difficulty clearing secretions, especially during respiratory illnesses. Manual-assisted cough training and cough-assist devices should be recommended when needed by pulmonology. Consider a cough-assist device when the boy is in a wheelchair full time, has difficulty clearing respiratory secretions, has a weak cough, and/or gets frequent respiratory illnesses. See Breathing & Cough Assist Devices - Letters of Medical Necessity (Dr. Bach) for information about getting these devices approved by insurance.
Assisted nighttime ventilation
Several studies have suggested that assisted nighttime ventilation (non-invasive intermittent positive pressure ventilation or IPPV) can improve general health and life expectancy; boys with DMD may notice less frequency of chest infections, more energy, and better sleep. [Bach: 1995] However, respiratory muscle weakness will continue to progress. Assisted daytime ventilation will become necessary during illnesses and then more regularly. Intervention may be by non-invasive techniques or tracheostomy, depending on local experience and patient/family preferences. See DMD Respiratory Care Consensus Statement (ATS), [Finder: 2004] and [Birnkrant: 2010].
Some patients and their families choose not to pursue assisted ventilation. Families should be counseled about options and supported in their choices.

Rehab/Mobility/Function

Joint contractures
When first diagnosed, a majority of patients have tight heel cords and a history of toe-walking. An orthopedic surgeon experienced in the care of children with DMD should be consulted to follow this problem and initiate treatment. Treatment might include ankle-foot orthoses (AFOs), heel cord stretching exercises, night splinting, and/or serial casting. At some point, surgery may be necessary to lengthen heel cords, despite other treatments. Some investigators suggest waiting until the fixed deformity is greater than 20 degrees, whereas others suggest early prophylactic muscle/tendon lengthening procedures. In boys with significant weakness, the risk of losing ambulation exists due to a prolonged non-weight-bearing period after surgery. Surgery should be considered carefully in light of this risk, and if performed, early mobilization is imperative. Reasons to consider surgery include:

Heel cord lengthening may prolong the ability to walk
Preventing foot deformities after wheelchair confinement may help with positioning and allow continued shoe-wearing

Surgery usually involves performing a tenotomy of the Achilles tendon and the posterior tibial tendon, followed by 4-6 weeks in a cast, after which a solid AFO is worn. Some orthopedic surgeons advocate posterior tibial tendon transfer to the dorsum of the foot to allow the child to be brace-free after the surgery.

As the disease progresses, contractures may also develop at the knees and hips, leading to difficulty with wheelchair seating, discomfort while sleeping, and skin ulcers. Stretching exercises may be useful in delaying these contractures. Occasionally, contractures may require surgical correction (i.e., hip flexor-abductor releases, distal hamstring releases).

Wheelchairs and other equipment
Begin thinking about a wheelchair or other mobility device when falls are frequent, the boy is having difficulty getting up from the floor, and/or when limitations on how far he can walk begin restricting participation in family and community life. Some families prefer scooter use early on, while others prefer a lightweight or folding wheelchair or stroller-type wheelchair. Insurance companies may limit wheelchair purchases to 1 every few years and will sometimes not buy a manual wheelchair after a power chair has been purchased. Therefore, providers and families should order a manual wheelchair when the need first becomes apparent and a power wheelchair when mobility is further compromised. Although the family is sometimes reluctant to get the first wheelchair, the child is often happy to have the increased mobility and independence. Fitting a wheelchair, getting letters of medical necessity (often written by the physical therapist), obtaining insurance preauthorization, and ordering and receiving the wheelchair can take up to 6 months, so the process should be started when the need is first recognized. See Wheelchairs and Adapted Strollers and Working with Insurance Companies. Sometimes a local resource, such as an MDA Clinic or Shriners Hospital, will have a loan closet of equipment or may be able to find a loaner or permanent wheelchair if the child is at risk while waiting for the wheelchair.

In adolescence and beyond, families will often need additional equipment, including bath chairs, slides, power lifts, and commode systems. Physiatrists and physical and occupational therapists can help determine needs and the best equipment for the family, as well as help with insurance preauthorization. Sometimes organizations such as the MDA Clinic and Shriners Hospitals will have donated equipment for families without financial resources.

Scoliosis
Scoliosis and/or compression fractures should be monitored on a regular basis, at least yearly, in non-ambulatory boys. Older boys with DMD exhibit scoliosis 90-95% of the time; the age of onset is variable, and the incidence is much decreased in those who have been on steroids. Trunk muscles progressively weaken, leading to collapse of the spine into a long C-shaped curve. In addition to seating problems and discomfort, scoliosis can lead to respiratory compromise due to decreased lung volume. A spine exam and spine X-rays (sitting anteroposterior spine) should be performed routinely after age 10 or when patients become non-ambulatory. Scoliosis surgery is recommended when the curvature measures 20 to 30 degrees; bracing is not thought to be helpful and is poorly tolerated. Scoliosis correction is major surgery and should be performed before pulmonary or cardiac function is too compromised. Spine X-rays will also show non-symptomatic vertebral fractures; if present, boys should be referred to an osteoporosis expert for IV bisphosphonate therapy. See Osteoporosis and Pathologic Fractures.

Nutrition/Growth

Young children with DMD may exhibit decreased weight due to decreased muscle mass; older boys with DMD, especially those on steroids, may be obese, although a normal BMI is the goal. Body surface area may be needed for steroid dosing and can be calculated from weight and height. Height should be measured in a standardized fashion according to clinic preference in children in wheelchairs.

Diet and obesity
Nutrition and the prevention of obesity should be discussed early and often. As the child grows and develops, dietary and caloric needs should be routinely evaluated. Obesity, often independent of steroid use, may be seen as early as age 7; its prevalence seems to peak in the early teens at about 54%. [Willig: 1993] Obesity makes movement and activity even more difficult. Undernutrition may also be seen after the age of 14 years due to weakness and incoordination of the muscles used in chewing and swallowing. When possible, involve a nutritionist for underweight or overweight boys. Urinary or blood monitoring for impaired glucose tolerance should be performed periodically for boys on steroids.

Exercise
Boys should be instructed to maintain cardiovascular conditioning, enhance bone health through activities such as walking and swimming, and begin a stretching program. Boys with DMD should avoid body-building type (isometric) exercises, such as weight lifting. Writing a note or communicating directly with physical education teachers regarding limitations and exercising might be necessary.

Endocrine/Metabolism

Osteoporosis in DMD
Boys with DMD, particularly those that have been treated with glucocorticoids, are prone to developing osteoporosis, which clinically manifests as low-trauma vertebral or long-bone fractures. Although initially deflazacort was thought to be bone sparing, this may not be true, and the same standards of management apply to boys on either prednisone or deflazacort.

Long bone fractures can lead to permanent loss of ambulation and have been associated with fat embolism syndrome. Vertebral fractures may sometimes be asymptomatic. If untreated, it can lead to chronic back pain and spine deformity. New guidelines recommend early detection with treatment of osteoporosis before it progresses. All boys with DMD should get yearly spine imaging whether or not they have back pain or deformities. If fractures are found, they should be referred to Pediatric Endocrinology. Other measures, such as calcium and vitamin D intake and 25-hydroxyvitamin D level, should be assessed at baseline and annually and improved as needed.

Intravenous bisphosphonates are indicated for the treatment of low-trauma vertebral fractures or long-bone fractures and should be treated by a bone metabolism expert in Pediatric Endocrinology. Various options, including IV zoledronate and pamidronate, are available depending on the experience of the endocrinologist. Treatment often includes hospital admission for the first infusion and at regular intervals thereafter, depending on the choice of medication. Prior to starting intravenous bisphosphonate therapy, calcium and vitamin D deficiency should be corrected, and normal renal function should be confirmed. [Birnkrant: 2018] See Osteoporosis and Pathologic Fractures

Growth hormone deficiency
Many boys with DMD have poor linear growth exacerbated by chronic corticosteroid treatment. If growth hormone deficiency is suspected from growth chart data, an IGF1 and an IGFBP3 should be performed, and if low, the boy with DMD should be referred to Pediatric Endocrinology (see NV providers [6]). At this time, routine use of growth hormone to treat growth failure in DMD without documented growth hormone deficiency is not recommended.

Testosterone replacement therapy
Delayed puberty can often be seen in boys with DMD. Boys with delayed puberty should be referred to Pediatric Endocrinology after a pubertal exam confirms the lack of pubertal change by age 14. Bone age X-ray is performed to accompany the referral.

Testosterone replacement therapy may be considered for boys who are not developing secondary sexual characteristics by age 14. Testosterone, if prescribed, is initiated at a low dose and increased over time for physiologic replacement. It is given by IM injection monthly, bi-monthly, or weekly. Topical preparations can eventually be used. A gradual increase allows normal physiological development, including the pubertal growth spurt, and may be helpful in preventing or mitigating osteoporosis. [Birnkrant: 2018] [Arslanian: 1997]

Gastro-Intestinal & Bowel Function

For unclear reasons, individuals with DMD frequently have problems with constipation and bladder continence, including urgency and hesitancy. Because of difficulties surrounding toileting at school, many boys will decrease fluid intake, which, in turn, worsens constipation and increases risk for renal stones. Boys with DMD should be included in problem-solving toileting issues to increase their comfort and safety and allow adequate fluid intake. Many PM&R doctors and physical and occupational therapists have experience with toileting in individuals with disabilities. See:

Dental

Boys with DMD will need an experienced pediatric dentist or a dentist with expertise in children with special health care needs. Dental care should begin early to prevent problems and maintain good oral hygiene. Boys with DMD have many reasons to have difficulty with oral hygiene. Jaw muscles may weaken as the disease progresses, leading to increased plaque buildup and dental caries. Orthodontic needs are common and include widening of the jaw and increasing spacing between the teeth. As time goes on, boys may not be physically able to bring a toothbrush up and manipulate it for brushing. When necessary, adapted assistive devices should be prescribed, or a caregiver may need to do the brushing. Electric toothbrushes may also be helpful. For more information, see Dental and Oral Health Screening and Dental Care for Boys with DMD (Parent Project MD).

Development

Boys with DMD often present with gross motor and language developmental delays. Although motor milestones are achieved in a delayed manner, most children with DMD walk by 18 months of age. By preschool, they exhibit slower motor skills and are less able to keep up with their peers. They may fall frequently compared to their peers and use the Gowers' maneuver to get up from the floor and handrails to go upstairs. Children with developmental delays should be referred to early intervention programs and receive therapy as indicated. Signs of autism may be observed in the early years and should be evaluated and managed appropriately.

Learning/Education/Schools

Boys with DMD may have intellectual disability and/or features of autism that impair learning. Recent investigations suggest that older reports of a decreased mean IQ may have instead reflected problems with short-term verbal memory and executive function. [Anderson: 2002] [Hinton: 2001] The learning problems do not worsen as the muscle weakness progresses – for unknown reasons, there may even be improvement. Problems may be noted in processing and retrieval of information, attention deficits, phonological coding problems, and decreased emotional interaction. [Cotton: 2005] A full psychological evaluation, including achievement and IQ testing, is recommended for those with problems in school. All children with DMD should have School Accommodations: IEPs & 504s plan(s) to optimize academic goals and support communication, friendship, and recreational activities at school. These should cover the following:

Special transportation needs (Transportation and Travel for People with Disabilities)
Toileting issues
Class placement (e.g., mainstreaming vs. a special education class)
Responsibility in case of a school emergency
Therapy needs
Physical education restrictions

IEPs and 504 plans are modified as needed and reviewed annually. School progress should be monitored as part of periodic routine clinic visits. Individuals with BMD do not usually have cognitive problems, or if present, they are not as severe. [Darras: 2008] as those in DMD.

Mental Health/Behavior

Boys with DMD are at an increased risk for depression and anxiety. Screening questionnaires for mental health problems and quality of life should be administered frequently. Standard evidence-based practices, including medication and therapy, should be used. Families may also have depression and anxiety and should be referred to resources as needed. The following have links to screens and management information:

Transitions

As boys with DMD approach adolescence, it is important to work with the youth and family to plan the transition to adult life and adult health care. With proactive health care and/or steroid treatment, boys with DMD are living longer; it should be assumed they will reach adulthood. After school is completed, the living situation needs to be considered. Options include home, independent living, a group home, or a nursing home environment, depending on medical needs. Vocational and recreational opportunities should be explored by the family. Some boys with DMD will need the family to obtain at least partial guardianship, and this should be applied for when the boy turns 18. Financial services may change at age 18 as well, and experts at Medicaid, SSI, and other benefits should be consulted.

In response to increasing awareness of transitional issues, the MDA has initiated a transition program targeted at adolescent and young adult patients with neuromuscular disease. Goals of the program include empowering patients and families through access to information and services. See the MDA Young Adult Programs. Hospice & Palliative Care (see NV providers [26]) should be consulted as needed. Make-A-Wish Foundation may also be appreciated by boys with DMD and their families.

Services & Referrals

Neuromuscular Clinics (see NV providers [2])
A multidisciplinary approach for care of boys with DMD is preferred. These clinics also may be involved in research protocols for treatment of children with DMD. List of MDA Care Centers (MDA) has clinic locations and local details.

Pediatric Orthopedics (see NV providers [8])
Consider referral for baseline evaluation, routine spine X-rays, and management of contractures, gait problems, scoliosis, and the need for equipment for ambulation, such as walkers. Initially, these visits may be every year, but as the disease progresses, the child may need to be seen at 6-month intervals.

Pediatric Endocrinology (see NV providers [6])
Consider referral if vertebral fractures are found on spine X-rays, even non-symptomatic ones, for consideration of IV bisphosphonate therapy. Endocrinology referral may also be important if puberty is delayed or if there is concern for adrenal insufficiency or growth hormone deficiency.

Pediatric Physical Medicine & Rehabilitation (see NV providers [3])
A referral may help in the evaluation of contractures, gait problems, and obtaining aids for ambulation. Physical medicine and rehabilitation may be available at MDA Clinics.

Physical Therapy (see NV providers [9])
Periodic visits can help to evaluate and maintain abilities. Frequency of visits should be based on many factors (need, financial resources, availability, and access) and balanced with treatment goals (ranging from post-surgical PT to a home-therapy program taught to the parents).

Pediatric Cardiology (see NV providers [4])
Boys with DMD and BMD should receive cardiac evaluation with echocardiogram (or MRI) and EKG at diagnosis and then yearly unless clinical circumstances mandate more frequent visits.

Pediatric Pulmonology (see NV providers [4])
Boys with DMD should initially see a pulmonary specialist for a baseline evaluation and then visit regularly after loss of ambulation. Periodic screening may include pulmonary function testing and/or overnight oximetry. If overnight oximetry is abnormal, an overnight sleep study determines if NIPPV (non-invasive positive pressure ventilation) is needed. If needed, a specialist will fit the child with NIPPV equipment and determine settings. Cough strength should also be evaluated. Cough assist devices should be prescribed soon after the child becomes non-ambulatory.

Dieticians and Nutritionists (see NV providers [4])
Early referral should be made for patients who become overweight (which makes it more difficult for already weak muscles to move the body) or underweight (no reserve, risk of pressure ulcers). Ideally, dieticians should be available at Neuromuscular Clinics.

Pediatric Ophthalmology (see NV providers [6])
Children taking steroids should have periodic eye exams for cataracts.

ICD-10 Coding

G71.01, Muscular dystrophy

ICD-10 for Muscular Dystrophy (icd10data.com) provides further coding details.

Resources

Information & Support

Related Portal Content
The Medical Home Portal provides related general diagnositic and management information, including:

Answers to questions that families may frequently ask can be found at:

The Care Notebook may also be helpful for tracking medical history, test results, and records.

For Professionals

Dystrophinopathies (GeneReviews)
Detailed information addressing clinical characteristics, diagnosis/testing, management, genetic counseling, and molecular pathogenesis; from the University of Washington and the National Library of Medicine.

Muscular Dystrophy, Duchenne (OMIM)
Information about clinical features, diagnosis, management, and molecular and population genetics; Online Mendelian Inheritance in Man, authored and edited at the McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine

Neuromuscular Disease Center
Comprehensive website on neuromuscular diseases; Washington University, authored by Alan Pestronk, MD.

Muscle Weakness Video Library (childmuscleweakness.org)
This new resource was developed by Kathy Matthews, MD and the MDA, AAP, and other organizations; from the National Task Force for Early Identification of Childhood Neuromuscular Disorders.

All About Steroids with DMD (Parent Project MD)
Recommended care, monitoring and managing side effects, dosing, discontinuing use, and adrenal crises information for families who have boys on corticosteroids (prednisone or deflazacort) to treat DMD.

For Parents and Patients

Muscular Dystrophy Association
The Muscular Dystrophy Association (MDA) covers many conditions including CMT, Duchenne muscular dystrophy, and spinal muscular atrophy. More information about these conditions, how to register, and clinic locations can be found here.

Parent Project Muscular Dystrophy
Comprehensive site that covers the latest research, treatments, and related issues; site founded by family members of children with DMD.

Learning about DMD (National Human Genome Research Institute)
Information for families with a focus on genetics.

Muscular Dystrophy (CDC)
General information about MD for families that includes references to recent publications, extensive web resources, sites for kids, and genetic research for parents and families. Also includes current surveillance and research sponsored by the CDC to track incidence and treatment; Centers for Disease Control and Prevention.

Muscular Dystrophy (NINDS)
Information about muscular dystrophy, treatment, prognosis, research, and links to other organizations; National Institute of Neurological Disorders and Stroke.

Patient Education

Diagnosis & Management of DMD - Guide for Families ( PDF Document 1.8 MB)
Care standards based on the DMD published in the Lancet Neurology in 2010; contains many images and graphics, uses much ink if printed.

Care Checklist: Early Ambulatory Stage/Childhood (Parent Project MD)
For use by parents and caregivers of individuals with Duchenne muscular dystrophy to help you manage your child’s care if they are showing signs of Duchenne, like a waddling type of walk, walking on their toes, or needing to support themselves with their hands when they get up from the floor.

Care Checklist: Late Ambulatory Stage (Parent Project MD)
For use by parents and caregivers of individuals with Duchenne muscular dystrophy to help you manage your child’s care if they are having more trouble walking, getting up from the floor, and climbing stairs.

Care Checklist: Early Non-Ambulatory Stage/Childhood (Parent Project MD)
For use by individuals with Duchenne muscular dystrophy or their caregivers, to help manage care if needing a wheelchair for mobility.

Care Checklist: Late Non-Ambulatory Stage (Parent Project MD)
For use by individuals with Duchenne muscular dystrophy to help manage care if there is reduced upper limb function and difficulty maintaining good posture.

Tools

Imperatives for Duchenne: A Guide for Providers (Parent Project MD) ( PDF Document 133 KB)
One-page with essential considerations for clinicians treating boys with DMD.

Services for Patients & Families in Nevada (NV)

Service Categories	NV	NW		NM	RI
Dieticians and Nutritionists	4	1	1	3	7
Hospice & Palliative Care	26	3	5	4	42
Neuromuscular Clinics	2	1	1	3	3
Pediatric Cardiology	4		3	17	4
Pediatric Endocrinology	6	1	4	12	7
Pediatric Ophthalmology	6	1	6	8	4
Pediatric Orthopedics	8	4	7	16	10
Pediatric Physical Medicine & Rehabilitation	3	3	3	6	11
Pediatric Pulmonology	4		4	6	3
Physical Therapy	9		12	7	40

For services not listed above, browse our Services categories or search our database.

* number of provider listings may vary by how states categorize services, whether providers are listed by organization or individual, how services are organized in the state, and other factors; Nationwide (NW) providers are generally limited to web-based services, provider locator services, and organizations that serve children from across the nation.

Studies

Research in DMD (Parent Project Muscular Dystrophy)
Listing and explanation of clinical trials for DMD.

Clinical Trials in DMD (clinicaltrials.gov)
Studies looking at better understanding, diagnosing, and treating this condition; from the National Library of Medicine.

Helpful Articles

PubMed search for Duchenne or Becker muscular dystrophies in children, last 2 years

Weerkamp PMM, Mol EM, Sweere DJJ, Schrans DGM, Vermeulen RJ, Klinkenberg S, Hurks PPM, Hendriksen JGM.
Wechsler Scale Intelligence Testing in Males with Dystrophinopathies: A Review and Meta-Analysis.
Brain Sci. 2022;12(11). PubMed abstract / Full Text

Lee I, Turnage C, Sutyla R, Mitchell P, Lindahl H, Jesus A, Scharf RJ.
The Hidden Disease: Delayed Diagnosis in Duchenne Muscular Dystrophy and Co-Occurring Conditions.
J Dev Behav Pediatr. 2022;43(8):e541-e545. PubMed abstract

Birnkrant DJ, Bello L, Butterfield RJ, Carter JC, Cripe LH, Cripe TP, McKim DA, Nandi D, Pegoraro E.
Cardiorespiratory management of Duchenne muscular dystrophy: emerging therapies, neuromuscular genetics, and new clinical challenges.
Lancet Respir Med. 2022;10(4):403-420. PubMed abstract

McDonald CM, Mercuri E.
Evidence-based care in Duchenne muscular dystrophy.
Lancet Neurol. 2018;17(5):389-391. PubMed abstract

Authors & Reviewers

Initial publication: December 2013; last update/revision: March 2023

Current Authors and Reviewers:

Author:	Lynne M. Kerr, MD, PhD
Reviewer:	Russell Butterfield, MD, PhD

Authoring history

2020: update: Lynne M. Kerr, MD, PhD^A; Mary A. Murray, MD^CA; Vandana Raman, MD^CA; Russell Butterfield, MD, PhD^R

2013: first version: Lynne M. Kerr, MD, PhD^A; Russell Butterfield, MD, PhD^A

^AAuthor; ^CAContributing Author; ^SASenior Author; ^RReviewer

Page Bibliography

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GeneReviews (NIH); (2008) http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=dbmd.

Feingold B, Mahle WT, Auerbach S, Clemens P, Domenighetti AA, Jefferies JL, Judge DP, Lal AK, Markham LW, Parks WJ, Tsuda T, Wang PJ, Yoo SJ.
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Respiratory Care of the Patient with Duchenne Muscular Dystrophy.
The official statement of the American Thoracic Society; (2004) https://www.atsjournals.org/doi/10.1164/rccm.200307-885ST?url_ver=Z39.....
This statement is designed to educate the practitioner about new approaches to therapies available for the management of the respiratory complications of DMD. In addition to respiratory care, it covers sleep evaluation, nutrition, cardiac involvement, scoliosis and corticosteriods. It also discusses end-of-life care and the decision to use or not use a respirator.

Flanigan KM, Dunn DM, von Niederhausern A, Soltanzadeh P, Gappmaier E, Howard MT, Sampson JB, Mendell JR, Wall C, King WM, Pestronk A, Florence JM, Connolly AM, Mathews KD, Stephan CM, Laubenthal KS, Wong BL, Morehart PJ, Meyer A, Finkel RS, Bonnemann CG, Medne L, Day JW, Dalton JC, Margolis MK, Hinton VJ, Weiss RB.
Mutational spectrum of DMD mutations in dystrophinopathy patients: application of modern diagnostic techniques to a large cohort.
Hum Mutat. 2009;30(12):1657-66. PubMed abstract

Gloss D, Moxley RT 3rd, Ashwal S, Oskoui M.
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Neurology. 2016;86(5):465-72. PubMed abstract / Full Text

Guglieri M, Bushby K, McDermott MP, Hart KA, Tawil R, Martens WB, et al.
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Helderman-van den Enden AT, de Jong R, den Dunnen JT, Houwing-Duistermaat JJ, Kneppers AL, Ginjaar HB, Breuning MH, Bakker E.
Recurrence risk due to germ line mosaicism: Duchenne and Becker muscular dystrophy.
Clin Genet. 2009;75(5):465-72. PubMed abstract

Hinton VJ, De Vivo DC, Nereo NE, Goldstein E, Stern Y.
Selective deficits in verbal working memory associated with a known genetic etiology: neuropsychological profile of DMD.
J Int Neuropsychol Soc. 2001;7(1):45-54. PubMed abstract / Full Text

Houde S, Filiatrault M, Fournier A, Dubé J, D'Arcy S, Bérubé D, Brousseau Y, Lapierre G, Vanasse M.
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Cochrane Database Syst Rev. 2008(1):CD003725. PubMed abstract

Markham LW, Kinnett K, Wong BL, Woodrow Benson D, Cripe LH.
Corticosteroid treatment retards development of ventricular dysfunction in Duchenne muscular dystrophy.
Neuromuscul Disord. 2008;18(5):365-70. PubMed abstract

McDonald CM, Mercuri E.
Evidence-based care in Duchenne muscular dystrophy.
Lancet Neurol. 2018;17(5):389-391. PubMed abstract

Merlini L, Cicognani A, Malaspina E, Gennari M, Gnudi S, Talim B, Franzoni E.
Early prednisone treatment in Duchenne muscular dystrophy.
Muscle Nerve. 2003;27(2):222-7. PubMed abstract

Romitti PA, Zhu Y, Puzhankara S, James KA, Nabukera SK, Zamba GK, Ciafaloni E, Cunniff C, Druschel CM, Mathews KD, Matthews DJ, Meaney FJ, Andrews JG, Conway KM, Fox DJ, Street N, Adams MM, Bolen J.
Prevalence of Duchenne and Becker muscular dystrophies in the United States.
Pediatrics. 2015;135(3):513-21. PubMed abstract / Full Text

Schram G, Fournier A, Leduc H, Dahdah N, Therien J, Vanasse M, Khairy P.
All-cause mortality and cardiovascular outcomes with prophylactic steroid therapy in Duchenne muscular dystrophy.
J Am Coll Cardiol. 2013;61(9):948-54. PubMed abstract

Simonds AK, Muntoni F, Heather S, Fielding S.
Impact of nasal ventilation on survival in hypercapnic Duchenne muscular dystrophy.
Thorax. 1998;53(11):949-52. PubMed abstract / Full Text

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Neuromuscul Disord. 2010;20(8):499-504. PubMed abstract / Full Text

Willig TN, Carlier L, Legrand M, Riviere H, Navarro J.
Nutritional assessment in Duchenne muscular dystrophy.
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