Development in the first few years of life is typically normal, with milestones achieved at a slightly delayed if not normal rate. Growth velocity, however, is slower, leading to short stature. Mild hypotonia in an infant may be present, and poor head control in an infant may be an initial sign. Patients do not have atypical facies, but with the onset of facial muscle weakness, a transverse or horizontal sign may be seen in later childhood. Weakness and difficulty in ambulation in typically first noted between 2 and three years of life. This manifests as toe walking, difficulty running, climbing up stairs, and frequently falling. Weakness is more pronounced in proximal than distal muscles and the lower limb more than the upper limb.

In ambulatory patients, an increased incidence of fractures is noted as a consequence of the frequent falls.

Lumbar lordosis and scoliosis with muscle contractures occur. As a result of scoliosis, pulmonary function may be impaired, which can lead to pulmonary compromise.

Contractures of the ankles, knees, hips, and elbows may be seen.

Enlargement of the calves with wasting of the thigh muscles results in pseudohypertrophy of the calves, which is a classical feature. Aside from the calves, hypertrophy of the tongue and muscles of the forearm may be seen but are less classical.

A waddling or Trendelenburg gait is common, and patients must use a wheelchair by the age of 12.

Pharyngeal weakness can result in episodes of aspiration, nasal regurgitation of liquids, and a nasal quality of voice.

Incontinence of urine and stools due to urethral and anal sphincter weakness is uncommon and, if present, is a late manifestation.

Rarely, malignant hyperthermia after anesthesia may be a presenting sign.

Symptomatic female carriers may have an early onset and progressive muscular dystrophy.

Intellectual Disability

Intellectual impairment is seen in all patients; however, only 20% to 30% of patients have an intelligence quotient (IQ) less than 70. The degree of impairment does not correlate with disease severity. Most patients have only a mild form of learning impairment and can function in a regular classroom. Epilepsy is more common than in the general population, and uncommonly, autism-like behavior has been described.

DMD Associated Cardiomyopathy

Symptoms of cardiomyopathy can develop in the early teens and are present in almost all patients in their twenties. Persistent tachycardia and heart failure, maybe presenting signs. In affected patients, dilated cardiomyopathy is characterized by extensive fibrosis of the posterobasal left the ventricular wall. As the disease progresses, fibrosis can spread to the lateral free wall of the left ventricle. With the involvement of the posterior papillary muscle, significant mitral regurgitation can occur.  Inter and intraatrial conduction abnormalities, possibly involving the AV node, can be seen. Arrhythmias, particularly supraventricular arrhythmias, are also associated with the developing cardiomyopathy.

Physical exam shows pseudohypertrophy of the calf muscle and occasionally the quadriceps muscle. Shortening of the Achilles tendon may be noted, and the patient may have hyporeflexia or areflexia. Ankle reflexes are preserved till late in the disease unless contractures develop. Knee deep tendon reflexes (DTR’s) are less brisk than the ankle and can be lost by age 6. The brachioradialis reflex is brisker than the biceps or triceps DTR’S. Typically, children are noted to use their arms to lift themselves from a seated position on the ground. This is known as Gowers sign.

A dystrophinopathy should be suspected in patients with symptoms of weakness, characteristic physical exam, and a possible family history of the disease. Laboratory testing involves creatinine kinase measurements, muscle biopsies, gene testing, and ECG findings for cardiomyopathy.[7][8][9]

Serum Creatinine Kinase (CK)

Serum CK measurements are elevated before the development of clinical symptoms and signs and may also be elevated in newborns. Levels peak by age two and can be more than 10 to 20 times above the upper limit of normal. As age and disease progress, serum CK levels decrease as fibrosis and fat progressively replace muscle. Other muscle enzymes, such as aldolase levels and AST levels, may also elevate.

Asymptomatic carriers may also have elevated CK levels. This is seen in about 80% of cases, and the highest levels are noted between ages 8 and 12.

Muscle Biopsy

A muscle biopsy will demonstrate endomysial connective tissue proliferation, scattered degeneration, and regeneration of myofibers, muscle fiber necrosis with a mononuclear cell infiltrate, and replacement of muscle with adipose tissue and fat.

The muscled biopsied are the quadriceps femoris and the gastrocnemius.

Electromyography

Characteristic myopathic features can be seen; however, this is nonspecific. Motor and sensory nerve conduction velocities are normal, and denervation is not present.

Gene Analysis

Patients with DMD demonstrate the complete or near-complete absence of dystrophin gene. Dystrophin immunoblotting can be used to predict the severity of the disease. In DMD, patients are found to have less than 5% of the normal quantity of dystrophin.

Polymerase chain reactions (PCR) can also be used and detect up to 98% of mutations. Multiplex ligation-dependent probe amplification (MPLA) is also used to identify duplications and deletions.  Duplications can lead to in-frame or out of frame transcription products. Fluorescence in situ hybridization (FISH) is used less frequently but is useful to identify small point mutations.

Dystrophin immunocytochemistry can also be sued to detect cases not identifies by PCR.

Electrocardiogram (ECG)

Characteristic ECG changes are tall R waves in V1-V6 with an increased R/S ratio and deep Q waves in leads I,aVL, and V5-6. Conduction abnormalities with arrhythmias may be identified with telemetry. As mentioned previously, supraventricular arrhythmias are more common. Intra-atrial conduction abnormalities are more common than AV or infra-nodal defects in DMD.

Echocardiogram

Evidence of dilated cardiomyopathy is present in almost all patients by the end of their teens or in their 20s.

No medical cure exists for this congenital dystrophy, and the disease has a poor prognosis. Treatment is centered on glucocorticoid therapy, prevention of contractures, and medical care of cardiomyopathy and respiratory compromise.[10][11]

Glucocorticoid Therapy

Glucocorticoid therapy decreases the rate of apoptosis of myotubes and can decelerate myofiber necrosis. Prednisone is used in patients four years and older in whom muscle function is declining or plateauing.

Prednisone is recommended at a dosage of (0.75 mg/kg per day or 10 mg/kg per week is given over two weekend days).

Deflazacort, an oxazoline derivative of prednisone, is sometimes preferred over prednisone as it has a better side effect profile and has an estimated dosage equivalency of 1:1.3 compared with prednisone. The recommended dosage is 0.9 mg/kg/day.

Studies have shown that glucocorticoid treatment is associated with improved pulmonary function, delayed development of scoliosis reduces incidence and progression of cardiomyopathy and overall improved mortality.

Cardiomyopathy

Treatment with angiotensin-converting enzyme (ACE) inhibitors and/or beta-blockers is recommended. Early studies suggest that early treatment with ACE inhibitors may slow progression of the disease and prevent the onset of heart failure.

Overt heart failure is treated with digoxins and diuretics as in other patients with cardiomyopathy.

Surveillance consists of a cardiology assessment with ECG and echocardiogram. This should be performed at the time of diagnosis or by the age of 6 years. Routine surveillance should be performed once every two years until the age of 10 and then yearly after that. If evidence of cardiomyopathy is present, surveillance every six months is indicated.

Pulmonary Interventions

Pulmonary function must be tested prior to the exclusive use of a wheelchair. This should be repeated twice a year once the patient reaches 12 years of age, must use a wheelchair or vital capacity is found to be less than 80% of predicted.

Orthopedic Interventions

Physiotherapy to prevent contractures is the mainstay of the orthopedic interventions. Based upon patient requirements, passive stretching exercises, plastic ankle-foot orthosis during sleep, long leg braces to assist in ambulation may be used. Surgery to release contractures may be required for advanced disease. Surgery to correct scoliosis may improve pulmonary function.

Nutrition

Patients are at risk for malnutrition, including obesity. Calcium and vitamin D should be supplemented to prevent osteoporosis secondary to chronic steroid use. DEXA scanning should be obtained at age three and then repeated yearly.

Exercise

Guidelines recommend all patients participate in a gentle exercise to avoid disuse atrophy. A combination of swimming pool and recreation-based exercises is recommended. Activity should be reduced if myoglobinuria is noted or significant muscle pain develops.

Novel Therapies

Gene therapies include medications that bind RNA and skip over the defective codon. This produces a shorter but potentially functional protein. Eteplirsen us an exon 51 skipping antisense oligonucleotides medications used for this purpose. Eteplirsen has been approved by the FDA for this purpose.

Beckers Muscular Dystrophy (BMD)

BMD has a later onset, and the length of survival is longer. Patients typically have higher concentrations of dystrophin protein.

Intermediate form of Muscular Dystrophy

Patients with this form of dystrophy have dystrophin levels between DMD and BMD.

Myotonic Muscular Dystrophy

Inherited as an autosomal dominant disorder, distal muscles are more commonly affected. The ability to walk is often preserved.

Limb-Girdle Muscular Dystrophy

This inherited dystrophy primarily affects muscles of the hip and shoulder girdles

Congenital Myotonic Dystrophies

This encompasses a group of inherited disorders associated with muscular dystrophy. The dystrophy is characterized by an increased severity at birth but has a benign course through life. There is a higher association with brain malformations. This includes diseases such as Ullrich type of muscular dystrophy, Fukuyama type of congenital muscular dystrophy, and muscular dystrophy associated with Walker-Warburg syndrome, to name a few.

The prognosis is typically poor for affected patients. Patients are often wheelchair dependent by the age of 12 years. Death occurs as a result of respiratory or cardiac complications in the teens or 20s. Other causes of death are pneumonia, aspiration, or airway obstruction.

The management of patients with DMD is best done with an interprofessional team that includes specialty trained nurses and therapists. Neuroscience and rehabilitation nurses participate in care, monitor patients, and report changes to the team. Primary care providers, physiatrists, and neurologists provide care. Orthopedists and thoracic surgeons may be consulted. Pharmacists review medication and check for drug-drug interactions. There is no cure for the disorder, and all the treatments are palliative. Palliative care physicians and nurses are eventually needed. The most important thing is to ensure that the patients lead a decent quality of life. Aggressive treatments may often do more harm than good.[12] [Level 5]