Duchenne muscular dystrophy (DMD) is the most common and most lethal muscular dystrophy. It is diagnosed in early childhood and affects 1 in 3600 to 6000 live male births.¹ It is an x-linked recessive, incurable disease caused by deletions and mutations in the dystrophin gene, which lead to a complete absence of the dystrophin protein or a wide range of functional protein expression (0%-5% of normal levels).² Duchenne muscular dystrophy is the most severe form of dystrophinopathy, with the clinical onset of weakness between the ages of 2 and 3 years,³ and it requires a lifetime of comprehensive care. Typically, patients with DMD are wheelchair bound by age 12 years and, without intervention, the mean age of death is 19 years.⁴ The most common causes of death in affected individuals are cardiorespiratory in nature.⁵ These patients’ daily lives are affected by DMD's other, but no less deleterious, symptoms and features: muscle weakness and contractures, dilated cardiomyopathy, scoliosis, and intellectual disability, to name a few. 

Becker muscular dystrophy (BMD), which is caused by mutations in the same gene, represents a milder form of dystrophinopathy due to higher degrees of functional dystrophin protein expression (5%-50% of normal levels).⁶ Some BMD patients are able to ambulate unassisted well into adulthood, with other symptoms and features, such as intellectual disability and contractures, that are less severe or absent.⁷ On average, muscle degeneration occurs 10 years later in BMD compared with DMD.⁸ Cardiomyopathy, however, tends to be more pronounced in BMD, possibly because these patients can perform much more strenuous exercise than those with DMD and thus severe cardiac muscle damage develops over time.⁹ 

The dystrophin gene is the largest human gene, composed of more than 2.5 million base pairs and 79 exons representing 0.01% of the entire human genome.^10,11 That dystrophin can be found in cardiac muscle, skeletal muscle, brain tissue, the retina, peripheral nervous tissue, and the kidneys may account for the full spectrum of devastating DMD symptoms.¹² The dystrophin protein is expressed at the sarcolemma of cardiac and skeletal muscle (Figure 1) where it interacts with integral membrane proteins assembled in the dystrophin–glycoprotein complex forming a bridge connecting the basal lamina of the extracellular matrix to the inner cytoskeleton.¹³ During muscular contraction, the dystrophin-glycoprotein complex provides the primary anchor point¹⁴ between the extracellular matrix and the actin filaments so that muscle contraction can result in motion—appropriately demonstrating the third tenet of osteopathic medicine: structure and function are reciprocally interrelated.¹⁵ This lack of proper anchoring is one of the main causes of progressive muscle damage occurring in patients with DMD. 

The objective of the present article is to provide osteopathic primary care physicians with the pathophysiologic mechanism of DMD, best approaches to early diagnosis, and current treatment options for patients. In addition, we highlight the challenges associated with access to care as well as the lack of an evidence-based, structured osteopathic approach to treating a patient with DMD and the need for further action by the osteopathic medical profession to address these gaps. 

Diagnosing DMD early in life is paramount for addressing future morbidity and mortality for the patient. The disparity between the lifespan of an untreated DMD patient and a treated DMD patient is around 20 years, demonstrating that treatment effectively doubles the lifespan.^1,4 Significant disparities in the timing of intervention exist in 2 areas: (1) presentation delay (time between initial caregiver concern and clinical evaluation, which averages 12 months) and (2) diagnostic delay (time between presentation to a health care professional and initial creatine kinase [CK] diagnostic screening).^16,17 Clinical suspicion is of the utmost importance in making a swift diagnosis and initiating early treatment, as initial caregiver concern typically precedes clinician awareness by about 1 year.^16,17 The most common reasons for initial concern include gross motor delay, muscle weakness, and difficulty walking, running, and climbing.¹⁶ Progression of DMD begins with lower extremity proximal muscle weakness, which is why walking, running, and climbing are affected first. Gowers sign (Figure 2) may also be present at the initial visit and is a sign of pelvic girdle weakness and instability.¹⁸ The average age of initial positive sign for DMD patients is around 5.5 years but can occur as early as 2 years.^19,20 While these are some of the most common presenting signs and symptoms, DMD's more devious symptoms typically manifest later. 

Performing a full physical examination in concert with a detailed osteopathic structural examination puts the osteopathic primary care physician (PCP) in a prime position to recognize the early signs of DMD. Positive findings of the general physical examination may include calf pseudohypertrophy, unique standing posture, grossly abnormal gait, Gowers sign, muscle contractures, or scapular winging. Muscle strength testing may indicate pelvic and shoulder girdle muscle weakness. Cognitive assessment may demonstrate intellectual disability, which can vary substantially for each patient.²¹ 

The osteopathic structural examination may provide crucial early signs of the disease, as it focuses mainly on the musculoskeletal system. A detailed inspection and palpation of the musculoskeletal system, which is a core link between the 5 coordinated body functions, provides a natural entry point for diagnosis and treatment.²² The osteopathic structural examination may reveal tissue texture changes and somatic dysfunction in the lower extremity, upper extremity, or cardiorespiratory viscerosomatic reflex regions of the thoracic and upper lumbar spine. Palpation of the lower extremity muscles may reveal both boggy and ropy texture changes with underlying evidence of inflammation and fibrosis. Fascial examination may exhibit restriction in multiple planes in the proximal lower extremity, proximal upper extremity, and lumbar spine regions. Integrating these examination findings with patient history may be helpful in narrowing the differential diagnosis and informing the osteopathic physician as to which diagnostic tests or symptomatic treatments will be most useful. 

Although DMD is rapidly progressive, treatments are now able to substantially extend life expectancy. Therefore, minimizing diagnostic delay is imperative. Creatine kinase levels are an early and sensitive indicator for skeletal muscle damage, particularly in concert with elevated amino transferase levels.²³ In patients with DMD, CK levels are about 15 times the normal upper limit (often much higher) and typically peak around age 3 years.⁸ Determining the CK levels in a young patient who presents with the aforementioned signs and symptoms is of paramount importance, as early diagnosis of DMD could potentially add 2 decades to the patient's lifespan.⁴ 

After identifying extensive skeletal muscle damage and obtaining CK levels, the PCP should order genetic testing to determine the type of muscular dystrophy and the specific mutation or deletion present in the patient.^1,24 Knowing the type of muscular dystrophy allows for discussion of available treatment options and future family planning.²³ Muscle biopsy, electromyography, and nerve conduction studies may also be performed as part of the diagnostic workup but are not always necessary for a definitive diagnosis.¹ 

While the present article is not meant to provide a comprehensive review of symptomatology, knowledge of the pertinent symptoms that may occur and persist along the clinical course is important. Dysfunctions are common in the neuromuscular, pulmonary, cardiac, and cognitive systems. Skeletal muscle degeneration with disabling progressive muscle wasting and rapid loss of mobility begins relatively early in the clinical course. Respiratory muscle function declines rapidly in the latter stages of the clinical course, resulting in respiratory failure and frequent respiratory tract infections, which contribute to early death.^5,25 All muscle types are affected, while smooth muscle and cardiac muscle tend to be affected later in the disease course.²⁶ Additionally, as a result of muscle dysfunction and deformities, pain is common in patients with DMD. The pain can be mild to moderate in intensity; occurs in the lower back, spine, and legs; and is typically underestimated by the physician.²⁷ As one of the most important quality of life measures, pain must be addressed in the treatment plan. Cardiac abnormalities include conduction abnormalities and left ventricular fibrosis leading to dilated cardiomyopathy. Cardiomyopathy begins to affect these patients in a rapidly accelerating manner, with one-third of patients having symptoms at age 14 years and all patients having symptoms by age 18 years.²⁸ Cognitive function in patients with DMD can be extremely varied, but mild cognitive impairment and global developmental delay are common manifestations of the disease.^29-30 Considering the wide array of symptoms that affect the patient's life and the lives of those around the patient, coordination of care and treatment approach should attempt to address the full spectrum of the disease. 

Select medical centers have multidisciplinary teams that provide comprehensive care to patients with DMD and their families. This approach typically provides opportunity for the best outcomes.^1,31 However, for many patients, these resources are geographically and economically out of reach. For these patients, effective treatment hinges upon care coordination between PCPs, specialists, and other health care professionals. The Joint Principles of the Patient-Centered Medical Home³² charge the PCP with the role of principal care coordinator of the patient-centered medical home. This role of the PCP is particularly relevant in the case of the patient with DMD because the number of medical and ancillary services requiring coordination is immense. Bridging the gap between the 2 approaches (DMD multidisciplinary care team management vs PCP management) and their respective outcomes requires increased efforts by the PCP in providing psychosocial support, obtaining resources, balancing specialist recommendations, providing and managing treatments, and coordinating ancillary services. 

The treatment paradigm we propose (Figure 3) centers on the patient, the family, and the PCP. In this paradigm, the PCP is the cornerstone for effective, patient-centered treatment. The osteopathic PCP is uniquely equipped to diagnose muscular dystrophy and treat patients using osteopathic manipulative medicine (OMM) guided by the tenets of osteopathic medicine and informed by the 5 models of osteopathic patient care.²² Patients with DMD have dysfunctions in all 5 body physiologic functions and, therefore, would be best approached and optimally treated by relying on all 5 models of osteopathic care. 

Applying the behavioral approach to this paradigm, the PCP is one of several people that support and care for the patient. The relationship between the caregivers and the physician is crucial. The PCP educates and empowers caregivers so that they can provide the best informed care and support to the patient, and the caregivers share their observations and abilities with the PCP to further informed care. Decision making and care that involve the family has been shown to improve outcomes on many levels.³³ 

In accordance with the metabolic-energy model, addressing a patient's somatic dysfunctions combined with prescribing medications can aid in improving and stabilizing metabolic and systemic functions²² of a patient with DMD. The landscape of novel DMD pharmacologic interventions is rapidly changing and consistently aiming to provide life-extending advances. The mainstays of treatment, however, are generally focused on supportive care and do not address the underlying cause.¹ 

Currently available pharmacologic treatments can be broken down into categories based on 4 desired outcomes: decreased muscle degeneration, preserved pulmonary function, preserved cardiac function, and increased dystrophin expression (Table 1). Regardless of a patient's disease progression, corticosteroids must be administered as soon as possible and continued throughout the clinical course.²³ Corticosteroids are the cornerstone of DMD treatment and attenuate disease processes in many different areas, including musculoskeletal degeneration, deteriorating pulmonary function, cardiac disease, and scoliosis progression.³⁴ 

Exon-skipping medications are one of the many types of interventions being explored in the management of DMD. In 2016, the US Food and Drug Administration approved eteplirsen, an exon skipping agent that targets mutations in exon 51.³⁵ Other novel dystrophin-increasing compounds that target other exons are in clinical trials, which are actively recruiting patients (Table 1). Some of these novel interventions have shown significant increases in dystrophin expression.³⁶ Considering that up to 83% of patients with DMD have mutations that are amenable to exon skipping,³⁷ clinical trials should always be considered viable treatment options for patients with DMD. Although some of these treatments have substantially extended patients’ lifespan, a cure is still lacking. Also, further pharmacologic treatments that target specific organ systems are typically initiated by a specialist in the respective field. 

Care for a patient with DMD requires the expertise of health care professionals from areas including neurology, cardiology, pulmonology, physiatry, orthopedics, gastroenterology, psychiatry, physical therapy, nutrition, and counseling, as well as other fields, such as complementary and alternative medicine.³⁸ Considering this large team, communication is integral to positive patient outcomes. However, effective communication does not typically occur in the absence of a facilitator or a forum. In the multidisciplinary DMD care team model, team meetings and communication protocols facilitate this interprofessional communication. Nevertheless, for the vast majority of patients who are unable to access this type of care, PCPs must facilitate specialist care. A list of resources is provided in Table 2; however, a single authoritative source for DMD treatment guidelines is still lacking in the United States. 

The osteopathic care arm of the treatment paradigm (Figure 3) represents any unique treatment modality that can be provided by an osteopathic physician alone. In particular, OMT has the potential to address derangements in any of the 5 physiologic functions. Patients with DMD would greatly benefit from an evidence-based comprehensive OMT protocol guided by the 5 models of osteopathic patient care, which is still lacking. A thorough literature search reveals no data specific to the application of OMT in patients with DMD. Nevertheless, OMT can be effective in addressing some of the specific consequences of the structural and musculoskeletal dysfunctions that are common in DMD, such as low back pain^39-41 and pneumonia.^42,43 Therefore, these and other symptomatic treatments should be considered for patients with DMD. 

Additionally, as DMD symptoms tend to appear well after clinically significant degeneration has already taken place, a thorough knowledge of underlying pathologic processes and the typical disease progression will aid in selection and application of treatment modalities. Certain direct treatments must be used with caution as repeated contraction (particularly eccentric contraction⁴⁴) and engagement of the direct barrier may result in additional muscle damage. Indirect modalities may be a safer approach to preventive treatment for contractures resulting from muscle damage. Using the neurologic model, considering manipulation to address autonomic regulation with techniques such as craniosacral manipulation⁴⁵ and rib raising⁴⁶ may prove useful in assisting in nervous system modulation.⁴⁷ Such modulation may also be helpful to patients whose nervous system is reciprocally affected by muscle and end organ damage. Lymphatic pump has been shown to increase lymphatic flow and immune mediators,^48,49 which would aid in managing infections and potentially peripheral edema, both of which are common in patients with DMD. 

Although OMT can be beneficial for many complications of DMD and has the potential to be an effective preemptive treatment, more studies that suggest treatment approaches and that investigate the safety and efficacy of particular modalities or regimens on this patient population are desperately needed. The American Osteopathic Association and the Muscular Dystrophy Association have formed a partnership in which osteopathic medical students and physicians can assist in camps for patients with muscular dystrophy across the United States. This partnership presents a unique opportunity for osteopathic physicians to learn more about muscular dystrophy and for patients to receive holistic, osteopathic care. 

Duchenne muscular dystrophy is a deadly and currently incurable disease that typically presents in early childhood. Early diagnosis is of utmost importance because advances in treatment have helped patients nearly double their lifespans. Ideally, DMD treatment centers, multidisciplinary teams, and up-to-date interventions would be available to all patients with DMD. However, such integrated care is not always possible. Osteopathic PCPs have bridged the gap in care availability for their patients for more than a century, and care for patients with DMD should be no exception. Approaching DMD care using this osteopathic primary care treatment paradigm makes up-to-date, holistic, and life-enhancing care possible in the hands of a competent PCP and a supportive family, regardless of geographic location or economic ability. 

We thank Raeann L. Carrier, PhD, for assistance on preparing this manuscript.