Duchenne and Becker Muscular Dystrophy

Overview

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, a muscle protein. Weakness is proximally predominant, but progression eventually involves distal muscles. Histopathologically, muscles are gradually replaced by fatty, fibrotic connective tissue. DMD is the most common and most severe form of the disease. Dystrophinopathies occur primarily in males; occasionally, female carriers demonstrate increasingly recognized manifestations, such as cardiac and motor issues, especially later in adulthood.

Boys with DMD present in the preschool years with proximal muscle weakness, difficulty walking, and large calves. Over time, muscle weakness worsens, resulting in loss of ambulation by 8 to 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. Susceptibility to respiratory infections and progressive deterioration of pulmonary function generally lead to premature death. Cardiomyopathy is universal, with onset in the early- to mid-teens. It is an increasingly important cause for mortality as affected individuals survive longer.

With improved anticipatory care, including the use of corticosteroids, non-invasive ventilation, and early treatment for scoliosis, survival is improving dramatically. In the past, most boys with DMD died in their late teens, usually from respiratory complications. Over the last decade, more individuals are surviving into their thirties. Increasingly, parent and provider groups are focusing on patient quality of life. 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, and primary care and emergency management. [Birnkrant: 2018]

BMD is milder and the onset is more variable than DMD. Boys with BMD can present with weakness later in childhood, adolescence, or even young adulthood. Progression is slower and life expectancy is longer, often mid to late adulthood. Cardiac problems are common in both boys and adults with BMD and may precede onset of muscle weakness.

Other Names & Coding

Dystrophinopathy
Pseudohypertrophic muscular dystrophy
ICD-10 coding

G71.01, Muscular dystrophy

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

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]

Genetics

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 it is 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. See Duchenne Muscular Dystrophy: Genetics.

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 eteplirsen, work only on specific mutations emphasizing the need for a confirmed genetic diagnosis. For more information, see Dystrophinopathies (GeneReviews), and Muscular Dystrophy, Duchenne (OMIM).

Prognosis

Boys with DMD usually become non-ambulatory in the early teen years and die in their late-20s to mid-30s of respiratory complications or cardiac complications. Life expectancy is improving and several treatments on the horizon may impact life expectancy a great deal. [Birnkrant: 2018] Oral corticosteroid use and proactive care of heart and respiratory issues, including early surgery for scoliosis if necessary and early use of non-invasive ventilation, have enabled affected boys to walk longer, live to adulthood, and make meaningful contributions to the community. Individuals with BMD often have a life expectancy into the 40s or later and walk into their 30s. 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]

Practice Guidelines

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

Roles of the Medical Home

A key role of the medical home is to coordinate care with a multi-disciplinary neuromuscular clinic. If not available, the medical home will need to ensure proper surveillance. The medical home will also be responsible for collaborating with subspecialists, monitoring for side effects from steroids (e.g., weight gain, behavior changes, osteoporosis, hypertension), and evaluating problems that need for further intervention, such as worsening shortness of breath, increasing difficulty walking, and developmental delay. The medical home may assist with Individualized Education Plans (IEP) or 504 plans (often needed for physical education and toileting); paperwork for a handicapped license plate (often downloadable from the state DMV website); and suggestions for parent support networks or local, state, and national resources. Continuing family education includes information about disease progression and emerging treatments. As respiratory complications arise, the medical home should help the family understand the risks and benefits of potential interventions.

Quality-of-life issues, mental health including anxiety/depression, and end-of-life directives are important to discuss, though some families may be uncomfortable doing so in their son's presence. Pain can also become a significant issue as affected children reach adolescence. The medical home can support the family regardless of their choice to intervene minimally or provide full ventilatory support (physicians often underestimate quality of life on a ventilator). [Gibson: 2001] (See Behavioral Management of Pain.) Referral to a hospice and/or wish-granting organizations may be appropriate. See Other Resources for wish-granting organizations, family resources, clinical tools, and educational materials.

Clinical Assessment

Overview

DMD is the most common childhood muscular dystrophy. Preschool-aged males with presentations that suggest DMD (usually gait instability and/or toe walking) should have a creatine kinase (CK) measured and receive a referral if indicated. Note that CK levels are very high, often over 10,000.

In addition to regular well-child checks and acute-care visits, boys with Duchenne, Becker, and intermediate muscular dystrophies need ongoing assessment in the following areas:
  • Strength and mobility
  • Cardiac
  • Pulmonary
  • GI/nutrition
  • Orthopedics
  • Bone density
  • Dental
  • Psychosocial
Coordinate care with a multidisciplinary neuromuscular clinic; if not available, the medical home will need to ensure proper surveillance. Assessment needs will change with steroid treatment since height/weight, bone mass, temperament, skin, eye exam (early cataracts with deflazacort), and susceptibility to infection may be affected. The Muscular Dystrophy Visit Checklist (PDF Document 41 KB) provides a printable visit checklist.

Pearls & Alerts for Assessment

Negative genetic testing

When clinical presentation is consistent with DMD, but genetic testing is negative, perform a muscle biopsy with dystrophin staining. 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. See Dystrophinopathies (GeneReviews). However, 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, absence of dystrophin staining on muscle biopsy confirms the diagnosis. Additional testing may be available in some centers on a research basis. This includes RNA sequencing from a muscle biopsy specimen that can identify the genetic mutation in most cases.

Females with DMD symptoms

Non-random inactivation of the X chromosome is likely responsible for the 8-10% of female manifesting carriers who have mild symptoms of DMD. [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, including proximal muscle weakness, tea-colored urine (myoglobinuria) on exertion, and high creatine kinases (generally in the thousands).

Mosaic carriers

During the initial evaluation of a boy with DMD, maternal genetic testing helps determine if the mother is a carrier. 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] [Bakker: 1989] Mothers testing negative for carrier status should be counseled about this possibility.

Mothers of boys with DMD

Even asymptomatic carrier mothers of boys with DMD may present with cardiac problems later in life. Mothers known to be carriers and those whose carrier status can’t be determined should be evaluated for early heart disease. Echocardiograms and EKGs are recommended every 5 years, and more frequently if abnormalities are found.

Screening

For the Condition

Efforts to include DMD in newborn screening are underway but complicated by the lack of widely applicable treatment for infants. [Mendell: 2013]

Of Family Members

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.

If carrier status is confirmed, prenatal testing and preimplantation diagnosis for subsequent pregnancies are available. For families who have not yet identified a mutation, have not had genetic testing, or are not interested in prenatal testing, check the CK of male infants several weeks after birth (it may be falsely high right after birth) to determine likelihood of DMD. Follow by genetic testing if the CK is abnormal.

For Complications

See the practice guidelines DMD Part 1: diagnosis and neuromuscular, rehabilitation, endocrine, and gastrointestinal and nutritional management [Birnkrant: 2018], Part 2: respiratory, cardiac, bone health, and orthopedic management [Birnkrant: 2018] and Part 3: primary care, emergency management, psychosocial concerns, and transitions of care across the lifespan [Birnkrant: 2018] for screening of the many associated complications/comorbidities.

Presentations

Patients typically present with proximal muscle weakness, manifesting as frequent falls, difficulty getting up from the floor, and large calves. The mean age of diagnosis of DMD without a family history is 4-5 years of age. Affected boys may also have developmental delay and toe walking. Symptoms are often identifiable by age 2, but diagnosis is delayed an average of 2.5 years. [Ciafaloni: 2009] 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).

Diagnostic Criteria

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.

Clinical Classification

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 not as important as understanding that they all are due to a mutation in the dystrophin gene and all will have progressive muscle weakness and, in many cases, cardiac problems. Literature is increasingly evaluating the links between genotype and phenotype in these disorders.

Differential Diagnosis

Given the high prevalence of DMD, a diagnosis of DMD is likely when, for example, there is a 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), polymyositis, and other muscle diseases. Genetic diagnosis provides definitive diagnosis in >95% of patients.

History & Examination

When the clinical presentation is typical of DMD, a marked elevation in creatine kinase (CK) allows a provisional diagnosis of DMD pending further testing. Typical CK levels at diagnosis range from 10-100 times normal. CK levels are not predictive of DMD vs. BMD, but CK elevation is generally not as high in boys with BMD. A high CK is not specific; it can be elevated in muscular dystrophies other than DMD/BMD/IMD.

Genetic testing is the gold standard for diagnosis. It provides a specific diagnosis, is non-invasive, may be helpful in counseling family members, and may guide treatment. Given the ease of genetic testing, dystrophin analysis on a muscle biopsy is very rarely needed. Absence of dystrophin on muscle biopsy is diagnostic for DMD but does not inform genetic counseling. If positive, the muscle biopsy should always be followed with genetic testing for mutations in the DMD gene. This is critical given that FDA-approved treatments, such as eteplirsen, are dependent on which mutation an individual has.

In earlier stages, monitor for muscle strength and endurance, and progression of contractures in ankle and hamstrings. Does the child fall frequently, have muscle pain after exertion, or get so tired the family does not bring him along on excursions such as shopping? Later on, look carefully for complications of muscle weakness, including muscle contractures, scoliosis, decubitus ulcers, cardiomyopathy, respiratory muscle weakness (cough strength), nocturnal hypoventilation, dysphagia, malnutrition/obesity, and constipation.

Current & Past Medical History

GI/nutrition: Ask about weight gain and loss, calcium and vitamin D intake, activity level, constipation and toileting at school, water intake, and any difficulty with choking or swallowing liquids or solids. Treatment with corticosteroids complicates nutritional issues and may result in significant weight gain, particularly as boys become less active. Weight loss issues become more significant in later stages when mechanical aspects of eating limit intake. This may necessitate placement of a feeding tube.

Muscle strength and mobility: Ask about progression of weakness and fatigue. If walking, do frequent falls or difficulty with short treks signal the need for a scooter or wheelchair? Can the family go to the grocery store or other places without needing a stroller? Can the child get up from the floor by himself? Is there difficulty negotiating stairs? Is the home wheelchair accessible? Does the family have a handicapped placard or license plate?

Cardiac/pulmonary: Any history of palpitations, shortness of breath, or dizzy spells? A sleep history (awakening, snoring, refreshed upon awakening, sleep position, AM headaches) can provide clues to possible nocturnal hypoventilation. The decreased activity of children in wheelchairs with end-stage disease can make cardiovascular symptoms difficult to notice.

Immune: With steroidal use, ask about problems with frequent or severe infections; and, for annual flu shots, use the injected killed virus variety, rather than the intranasal live virus.

Orthopedic manifestations: Any fractures? Contractures? Scoliosis? Recent visits to orthopedics? Last X-rays, Dexa scan results, if any?

Dental: Last dental exam/treatment?

Family History

Maternal uncles may have the disease or, more likely, will already have died of DMD. Older brothers may also be affected, in which case children may be genetically tested before birth or have a CK done several weeks after birth. CK should not be performed immediately at birth because delivery may raise the value even in boys without DMD. Families of children with DMD should have genetic counseling before future pregnancies. Boys with BMD may have uncles or brothers with BMD as well; except in rare circumstances, families do not have both BMD and DMD clinical presentations.

Pregnancy/Perinatal History

Pregnancies and deliveries of children with DMD/BMD/IMD are not distinctive.

Developmental & Educational Progress

Ask about gross motor and language delays. Cognitive delays are common in boys with DMD with full-scale IQs averaging 88. [Snow: 2013] School difficulties and/or learning problems should be inquired into in school-age children.

Maturational Progress

Puberty changes? Chronic treatment of oral corticosteroids can delay puberty. Toileting concerns with adolescence?

Social & Family Functioning

Exploring strengths and needs of the family of a child with newly diagnosed DMD/BMD/IMD will help the Medical Home anticipate family functioning in the future. Emotional status, depression? Behavior changes or attention problems if the boy is on steroids. Leisure activities? Family coping and resources? Autism spectrum symptoms?

Physical Exam

General

Boys with DMD are often quiet and rely on family members to answer questions. Look for Cushingoid facies if on steroid treatment. Look for signs of the wheelchair needing fitting or repair. (See Wheelchairs and Adapted Strollers.) Look for excessive hair growth if on steroids. Look for a withdrawn demeanor in adolescents that may signal depression and social isolation.

Vital Signs

BP | HR for changes secondary to steroid treatment. See Blood Pressure Percentiles for Boys (Medcalc3000).

Growth Parameters

HT | WT | BMI | BSA: Young children with DMD may exhibit decreased weight due to a 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.

Skin

Look for excessive acne and striae if the patient is on steroids.

HEENT/Oral

Deflazacort and prednisone are associated with early cataracts. Check for a robust red reflex bilaterally.

Chest

As weakness progresses, lung volume decreases. Check cough strength. Although subjective, a weak cough in the office should prompt further evaluation such as peak expiratory flow or other PFTs and a referral to pulmonology. Severe scoliosis can affect cardiopulmonary function.

Heart

Cardiac and pulmonary 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 easily fatigued.

Extremities/Musculoskeletal

Look for large calves, heel cord, and hip abduction contractures; a waddling lordotic gait with increased difficulty when trying to run; and difficulty getting up from the floor. See Gowers' Sign Video (YouTube). Observe for difficulty going up and down stairs. Muscles, especially those with pseudohypertrophy, may feel "woody." In non-ambulant patients, circulation can be impaired in the feet and lower legs (as they are often in a dependent position for long periods of time). Contractures appear – early on, ankle tendons are tight; later, contractures are also noted at the knee (hamstring) and the hips (hip flexors). Scoliosis is common.

Neurologic Exam

At diagnosis, look for proximal muscle weakness, decreased reflexes (although normal reflexes do not exclude diagnosis), normal sensory and cranial nerve exams. A waddling, wide-based, lordotic gait is typical, as the pelvis drops to the side of the leg being raised. There is often a forward curvature of the lumbar spine. Toe walking may also be noted, due to contractures of the heel cord. Boys may not be able to run, or the waddling might become more prominent when they try. With progression, boys will have increased difficulty with stairs and a more prominent Gowers' sign. Over time, boys will demonstrate decreased, symmetrical proximal muscle strength. Hip girdle muscles are affected first, followed closely by shoulder girdle muscle weakness. Muscles feel 'woody.' Muscles become atrophied and muscle mass is decreased. Walking becomes increasingly difficult; most children become non-ambulatory around 10-12 years of age, although this age is increasing in boys who are on steroids and can walk into the early teenage years. See excellent videos at 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.

Testing

Laboratory Testing

A very elevated creatine kinase (CK) is almost always present but is not specific for 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 diagnosis is established. The degree of elevation is not significant at diagnosis; for instance, a value of 20,000 in one patient does not indicate a more severe form of DMD than a value of 12,000 in another patient. Transaminases usually 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 abnormal clotting, are 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. CK should be checked early in any child with elevated transaminases, prior to extensive testing for liver disease.

CK is not as reliably elevated in boys with BMD, or in boys with advanced DMD and very low muscle mass.

Urinary or blood monitoring for impaired glucose tolerance should be performed periodically for boys on steroids.

Imaging

Imaging is not indicated for the diagnosis of DMD.

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 (eteplirsen) 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. For the most comprehensive genetic testing, see Genetic Testing Labs - Dystrophinopathies (GeneTests). If the genetic testing is negative but the clinical situation is highly suggestive of DMD, a muscle biopsy is recommended to confirm 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: Although common before genetic testing became widely available, muscle biopsy is not widely performed for DMD, but may also 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]

EKG and echocardiogram: At diagnosis, then annually, and preoperatively if undergoing general anesthesia at the discretion of the cardiologist

Cardiac MRI: Some cardiologists use an MRI to assess cardiac structure and function in boys with DMD. In older boys, or those with significant chest wall deformities, echocardiographic images may be limited, and a cardiac MRI will provide better functional assessment. In addition, using contrast agents with cardiac MRI allows assessment of scarring of the heart muscle.

Spine X-rays: Look for scoliosis or compression fractures at regular intervals.

PFTs and overnight oximetry: 1-2 times per year starting at age 5-6, more often as the boy becomes non-ambulatory

Ophthalmologic exam: Yearly, if the patient is on steroids

Specialty Collaborations & Other Services

Neuromuscular Clinics (see UT providers [6])

A multidisciplinary approach to care of boys with DMD is preferred. Muscular Dystrophy Association Care Center Clinics, which are sponsored by the Muscular Dystrophy Association, are found in many locations nationally and often have various subspecialists including genetic counseling, physical therapy, nutrition, respiratory therapy, and social work/care coordination. These clinics also may be involved in research protocols for treatment of children with DMD. See Find Your MDA Clinics (MDA.org) for clinic locations and local details.

Pediatric Neurology (see UT providers [5])

If a multidisciplinary clinic is not available, consider a referral to pediatric neurology with expertise in muscle disease for confirmation, genetic testing, counseling, and the initiation of treatment. Collaboration with the medical home should ensure visits at 6-month intervals to monitor the disease and order specific screening (e.g., ECHO and pulmonary function testing).

Pediatric Genetics (see UT providers [6])

Geneticists or genetic counselors help educate the family and determine the risk for subsequent children. Several visits may be needed to handle the large amount of information and to address new questions. Genetic expertise may be available in a multidisciplinary clinic for muscle disease.

Pediatric Orthopedics (see UT providers [18])

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 UT providers [5])

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 UT providers [11])

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.

Social Workers (see UT providers [3])

Families may need social work at diagnosis for counseling and finding available financial and community resources. Should be available on an ongoing, as-needed basis for questions about the emotional impact of the disease on the family and child, help negotiating available services (e.g., funding for a ramp to the home), and school issues.

Physical Therapy (see UT providers [54])

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 UT providers [7])

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 UT 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.

Nutrition Assessment Services (see UT providers [9])

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.

Bone Densitometry/DEXA (see UT providers [0])

Bone densitometry may be helpful. Although, current recommendations suggest that IV bisphosphonates be administered with even non-symptomatic vertebral fractures, discovered on routine spine films, and with lower extremity fractures.

Pediatric Ophthalmology (see UT providers [6])

Children taking steroids should have periodic eye exams for cataracts.

Treatment & Management

Pearls & Alerts for Treatment & Management

Steps before starting steroids

Before starting steroids, ensure immunity to chickenpox and test for tuberculosis, if warranted. Make sure all immunizations are up to date, especially pneumococcus. While on steroids, annual influenza shots should be injectable, killed-virus type.

Depolarizing muscle agents and anesthesia risk

Depolarizing muscle agents should be avoided during anesthesia due to risk of malignant hyperthermia. See [Birnkrant: 2007] and [Hayes: 2008].

Monitor nocturnal hypoventilation

Nocturnal hypoventilation can be monitored by taking a sleep history (awakening, snoring, refreshed upon awakening, AM headaches). Risk is significantly increased during the non-ambulatory phase of the disease.

Assess cough strength

Cough strength assessment should not be forgotten during appointments. Although subjective, if cough strength is weak, consider a pulmonology referral and/or a prescription for a cough-assist device.

How should common problems be managed differently in children with Duchenne and Becker Muscular Dystrophy?

Common Complaints

Respiratory symptoms: Boys with DMD, particularly those on steroids, and particularly as they get older, have respiratory compromise and are in more danger with even relatively minor respiratory illnesses. Parents should be aware of this fact and if an older boy with DMD becomes ill, he should be evaluated early by their medical home provider or the emergency room, depending on circumstances.

Other

Immunizations: Boys who are starting prednisone or deflazacort for Duchenne muscular dystrophy, about 5 years of age, should get all expected vaccinations for their age before starting these medications. Once on corticosteroids, annual influenza shots should be of the injectable, killed-virus type rather than the intranasal live virus.

Systems

Neurology

Long-term studies of boys with DMD show that corticosteroid treatment improves muscle strength and function, prolongs walking, and results in fewer complications, particularly scoliosis. [Gloss: 2016] Evidence suggests that steroids have a beneficial effect on respiratory and cardiac function. [Markham: 2008] [Bushby: 2005] [Schram: 2013]

Before starting corticosteroids, immunizations should be up to date 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 referral made to a dietician to determine typical calcium and vitamin D intake. If necessary, recommend dietary calcium and vitamin D supplements. See Calcium and Vitamin D.

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. Based on a small clinical trial (18 subjects), deflazacort is thought to have the same efficacy as prednisone but with a different side effect profile, including a higher incidence of cataracts but less weight gain and possibly a better behavioral profile. A larger double-blinded clinical trial comparing daily prednisone to daily deflazacort and 10 days on / 10 days off prednisone is in progress and nearing completion (FOR-DMD). In the US, significant interest in deflazacort has led some families to obtain supplies internationally for a modest cost. Recent approval by the FDA made deflazacort available in the US under the brand Emflaza, albeit at significant cost.

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 effect). The dose for deflazacort is 0.9 mg/kg/day. See [Houde: 2008]. Care guidelines recommend daily dosing, however some experts, while others prefer alternate regimens that may decrease side effects, particularly during the school week. An international group is attempting to determine a standardized corticosteroid treatment regimen. [Guglieri: 2017] Two alternate regimens are:
  • Alternating days, averaging at 0.75 mg/kg/day prednisone or 0.9mg/kg/day deflazacort.
  • Weekend dosing. A week's dose of given in 2 divided doses on weekend days.
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 of the side effects, such as weight gain and behavioral changes, can be managed without changing the steroid dose. Some, including weight gain that doesn't respond to treatment, unacceptable behavior problems, high fasting/postprandial glucoses or diabetes, confirmed persistent hypertension, or severe GI complications, will require dose reduction or stopping steroids.
Boys on steroids 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 if there are complaints of stomach pain or heartburn. Calcium carbonate tablets may be doubly useful as a calcium supplement and as an antacid.

Stopping Steroids

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-mobile since pulmonary and cardiac function may still benefit. [Balaban: 2005] In many cases, side-effects, especially weight gain, begin to accumulate after loss of ambulation. Patients and providers should carefully consider risks and potential benefits of continuing corticosteroid use after 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 glucocorticoids 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 prednisone a day, or the equivalent, places the individual at risk.

For boys on prednisone or deflazacort for treatment of DMD, 2 important issues concerning adrenal suppression need to be considered. First, corticosteroids, once started, cannot be stopped abruptly and need to be tapered over weeks to months to allow the hypothalamic-pituitary gland-adrenal gland axis to recover. Second, 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 with 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) has a protocol to guide providers in stress dosing.

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 who is in the process of tapering off steroids and/or is 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. Symptoms of insufficiency include hypotension, hyponatremia, hyperkalemia, nausea, abdominal pain, and/or hypoglycemia. [Bornstein: 2016] [Birnkrant: 2018] [Bowden: 2019]

Specialty Collaborations & Other Services

Neuromuscular Clinics (see UT providers [6])

Boys with DMD and BMD should be referred periodically to a multidisciplinary neuromuscular clinic, such as an MDA clinic, when available.

Pediatric Neurology (see UT providers [5])

When a multidisciplinary clinic is not available, consider a referral to pediatric neurology for treatment or co-management.

Pediatric Physical Medicine & Rehabilitation (see UT providers [11])

If not available at the multidisciplinary clinic, consider periodic referrals to physiatry to follow mobility issues and activities of daily living.

Physical Therapy (see UT providers [54])

Consider a baseline referral to physical therapy to evaluate and prevent contractures, maintain conditioning, and perform wheelchair fitting as needed. The frequency of visits should be guided by need, financial resources, availability, and access. Visits should be balanced with treatment goals (e.g., post-surgical PT or a home-therapy program taught to the parents).

Cardiology

Until recently, respiratory problems have been the leading cause of death in boys with DMD, but with better management of respiratory problems, individuals now live longer and more will experience significant cardiac problems. Cardiac complications also occur in Becker and intermediate muscular dystrophy; in fact, cardiac problems are the most common cause of death in individuals with BMD. [Darras: 2008] The most common cardiac problem is dilated cardiomyopathy, or an enlarged heart with poor squeezing function. When the echocardiogram (or MRI) 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 will often progress to heart failure, and cardiologists may add beta-blockers and diuretics. Left ventricular assist devices (LVADs) have been used in some cases, and may also be an option for boys with heart failure after careful consideration of risks and potential benefits.

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. See Duchenne Muscular Dystrophy: Cardiomyopathy.

Specialty Collaborations & Other Services

Pediatric Cardiology (see UT providers [7])

Baseline and subsequent periodic visits to pediatric cardiologists familiar with DMD are recommended for evaluation and treatment of cardiac complications.

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 necessary 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 Sample 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 on a more regular basis. Intervention may be by non-invasive techniques or by tracheostomy, depending on local experience and patient/family preferences. See DMD Respiratory Care (Consensus Statement, ATS) (PDF Document 102 KB), [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.

Specialty Collaborations & Other Services

Pediatric Pulmonology (see UT providers [4])

Evaluate for baseline lung function testing when approaching full-time wheelchair use. Annual or bi-annual visits may be helpful after age 12, after full-time wheelchair use, or if forced vital capacity is below 80% predicted.

Musculoskeletal

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 other investigators suggest early prophylactic muscle/tendon lengthening procedures. In boys who have significant weakness, the risk of losing ambulation due to a prolonged non-weight bearing period after surgery exists. 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).

Scoliosis
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 on a routine basis after the age of 10 years 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 expert in osteoporosis for the consideration of IV bisphosphonate therapy. See Missing link with id: c9cda7aa.xml and Osteoporosis and Pathologic Fractures.

Specialty Collaborations & Other Services

Pediatric Orthopedics (see UT providers [18])

Baseline evaluations and periodic visits with pediatric orthopedics are recommended for the management of contractures and scoliosis.

Pediatric Physical Medicine & Rehabilitation (see UT providers [11])

Periodic referrals to physiatry help maximize mobility and activities of daily living.

Hospitals (see UT providers [55])

Shriners Hospitals, where available, provide free orthopedic care to children with DMD.

Mobility/Function/ADLs/Adaptive

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 one 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 Writing Letters of Medical Necessity (general). 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 helping with insurance preauthorization. Sometimes organizations such as the MDA Clinic and Shriners Hospitals will have donated equipment for families without financial resources.

Specialty Collaborations & Other Services

Pediatric Physical Medicine & Rehabilitation (see UT providers [11])

If not provided in the neuromuscular clinic, refer to a physiatrist and physical and occupational therapists for periodic evaluation of mobility and daily living needs and help with equipment ordering and insurance preauthorization.

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. Boys with DMD should be included in problem-solving toileting issues to increase their comfort and safety and to allow continued adequate fluid intake. Many PM&R doctors and physical and occupational therapists have experience with toileting in individuals with disabilities. See:

Specialty Collaborations & Other Services

Pediatric Physical Medicine & Rehabilitation (see UT providers [11])

Helpful to evaluate and treat toileting issues in youths and young adults with DMD

Physical Therapy (see UT providers [54])

For evaluating equipment needs, such as adapted toilets and lifts

Occupational Therapy (see UT providers [39])

May be helpful for evaluating needs of daily living, such as toileting

Nutrition/Growth/Bone

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.

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

Growth Hormone Deficiency
Many boys with DMD have poor linear growth exacerbated by chronic steroid 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. 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 sometimes 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 osteoporosis. [Birnkrant: 2018] [Arslanian: 1997]

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 may lead to permanent loss of ambulation and, at times, 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.

Specialty Collaborations & Other Services

Pediatric Endocrinology (see UT providers [5])

Consider a referral if fractures, including vertebral fractures, are present for consideration of bisphosphonate treatment. Consider a referral if growth failure is present or if puberty is delayed after 14 years of age.

Nutrition Assessment Services (see UT providers [9])

Periodic visits with a nutritionist can help to avoid/manage nutritional deficits, overweight, and underweight, and to manage calcium intake.

Development (general)

Boys with DMD often present with gross motor and language developmental delays. Although motor milestones are achieved in a delayed manner, the majority of 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.

Specialty Collaborations & Other Services

Early Intervention for Children with Disabilities/Delays (see UT providers [53])

Can provide developmental evaluation and intervention in the preschool years

Developmental - Behavioral Pediatrics (see UT providers [8])

May assist in evaluating and monitoring development, and with tapping helpful community resources and coordinating their interventions

Learning/Education/Schools

Boys with DMD often have speech and language delays in the preschool years. Recent investigations suggest that older reports of a decreased mean IQ [Anderson: 2002] may have instead reflected problems with short-term verbal memory and executive function. [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 in those with problems in school. All children with DMD should have an Individualized Education Program (IEP) and/or 504 plan to optimize academic goals and support communication, friendship, and recreational activities at school. These should cover:
  • Special transportation needs
  • 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. For more information, see Education & Schools. Individuals with BMD do not usually have cognitive problems, or if present, they are not as severe. [Darras: 2008] as those in DMD.

Specialty Collaborations & Other Services

General Counseling Services (see UT providers [389])

To evaluate and suggest interventions for boys with DMD who are experiencing learning problems.

Neuropsychiatry/Neuropsychology (see UT providers [11])

To evaluate and suggest interventions for boys with DMD who are experiencing learning problems.

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 with the aim of preventing problems and maintaining 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 problems are common and include widening of the jaw and increased 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 Care for Boys with DMD (Parent Project MD).

Specialty Collaborations & Other Services

Pediatric Dentistry (see UT providers [65])

Dentists who have received training in caring for children with special health care needs as part of their pediatric dentistry fellowship are preferred.

General Dentistry (see UT providers [142])

Dentists who have interest or experience in caring for children with special health care needs are preferred.

Mental Health/Behavior

As 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.

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. The living situation, after school is completed, 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 transitions 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.

Specialty Collaborations & Other Services

Hospice & Palliative Care (see UT providers [48])

Programs can be very helpful for patients and families as debility encroaches on life span; can assist with making key choices regarding interventions and help family members cope.

Wish Foundations (see UT providers [23])

Provide children with serious illness and their families with trips, visits, gifts, and other services, usually on a one-time basis.

Issues Related to Duchenne and Becker Muscular Dystrophy

Funding & Access to Care

Writing Letters of Medical Necessity

Ask the Specialist

There is an 8-year-old boy with DMD on steroids in my practice. Should he get a flu shot, and do I need to treat him any differently if he gets the flu?

He should still get a flu shot, and if he has normal pulmonary status, he can be treated the same as other children in your practice. Older boys with DMD and pulmonary compromise are in more danger with any respiratory illness and should be treated more carefully with early referral for emergency care or to their pulmonologist.

If a 16-year-old young man with DMD in my practice is not showing any signs of puberty, is there something I can do?

Boys with DMD who are not showing signs of puberty by age 14 should be referred to Endocrinology.

Resources for Clinicians

On the Web

Dystrophinopathies (GeneReviews)
An expert-authored, peer-reviewed, current disease description that applies genetic testing to diagnosis and management information; sponsored by the U.S. National Center for Biotechnology Information, U.S. National Library of Medicine.

Muscular Dystrophy, Duchenne (OMIM)
Extensive review of literature that provides technical information on genetic disorders; Online Mendelian Inheritance in Man site, hosted by Johns Hopkins University.

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.

Adrenal Suppression for Boys on Steroids with DMD (Parent Project MD)
Information for families who have boys on corticosteroids (prednisone or deflazacort) to treat DMD.

Helpful Articles

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

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

Guglieri M, Bushby K, McDermott MP, Hart KA, Tawil R, Martens WB, Herr BE, McColl E, Wilkinson J, Kirschner J, King WM, et al.
Developing standardized corticosteroid treatment for Duchenne muscular dystrophy.
Contemp Clin Trials. 2017;58:34-39. PubMed abstract

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

Clinical Tools

Care, Action, & Self-Care Plans

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.

Patient Education & Instructions

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.

Resources for Patients & Families

Information on the Web

Duchenne Muscular Dystrophy (MedlinePlus)
A brief description for patients and their families of DMD, diagnosis, and management; from the National Library of Medicine.

Duchenne and Becker Muscular Dystrophy (Genetics Home Reference)
Detailed review of 2 major types of muscular dystrophy; sponsored by the National Library of Medicine.

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.

Consumer Guide to Hospice (WashingtonPost)
A consumer guide to hospices that participate in Medicare, searchable by state and county.

National & Local Support

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

Muscular Dystrophy Association
In-depth information about care, research, and support.

Studies/Registries

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

Clinical Trials in DMD (clinicaltrials.gov)
A list of trials registered with the National Institutes of Health; some may be of interest and offer the opportunity to participate in research.

Services for Patients & Families in Utah (UT)

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.

Authors & Reviewers

Initial publication: December 2013; last update/revision: August 2020
Current Authors and Reviewers:
Author: Lynne M. Kerr, MD, PhD
Contributing Authors: Mary A. Murray, MD
Vandana Raman, MD
Reviewer: Russell Butterfield, MD, Ph.D.
Authoring history
2013: first version: Lynne M. Kerr, MD, PhDA; Russell Butterfield, MD, Ph.D.A
AAuthor; CAContributing Author; SASenior Author; RReviewer

Bibliography

Anderson JL, Head SI, Rae C, Morley JW.
Brain function in Duchenne muscular dystrophy.
Brain. 2002;125(Pt 1):4-13. PubMed abstract

Arslanian S, Suprasongsin C.
Glucose-fatty acid interactions in prepubertal and pubertal children: effects of lipid infusion.
Am J Physiol. 1997;272(4 Pt 1):E523-9. PubMed abstract

Bach JR.
Respiratory muscle aids for the prevention of pulmonary morbidity and mortality.
Semin Neurol. 1995;15(1):72-83. PubMed abstract

Bakker E, Veenema H, Den Dunnen JT, van Broeckhoven C, Grootscholten PM, Bonten EJ, van Ommen GJ, Pearson PL.
Germinal mosaicism increases the recurrence risk for 'new' Duchenne muscular dystrophy mutations.
J Med Genet. 1989;26(9):553-9. PubMed abstract / Full Text

Balaban B, Matthews DJ, Clayton GH, Carry T.
Corticosteroid treatment and functional improvement in Duchenne muscular dystrophy: long-term effect.
Am J Phys Med Rehabil. 2005;84(11):843-50. PubMed abstract

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, 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

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Diagnosis and management of Duchenne muscular dystrophy, part 3: primary care, emergency management, psychosocial care, and transitions of care across the lifespan.
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