A muscular dystrophy is a group of more than 30 genetic diseases characterized by progressive weakness and degeneration of the skeletal muscles that control movement incorporates an assortment of hereditary disorders that lead to progressive, generalized disease of the muscle prompted by inadequate or missing glycoproteins in the muscle cell plasma membrane.[rx] Muscular dystrophy is a non-communicable disorder with abundant variations.[rx] Each has its pattern of inheritance, onset period, and the rate at which muscle is lost.[rx] Alterations in specific genes cause different representations of this disease.
Research has established that the gracilis, semimembranosus, semitendinosus, and sartorius muscles can be affected in patients with muscular dystrophy.[rx] Feet can exhibit an equinovarus deformity.[rx] The pelvis can tilt.[rx] There may be contractures throughout the body.[rx] Spinal deformities may produce lordosis or scoliosis.[rx] The eye can exhibit cataracts and bilateral ptosis.[rx]
Causes of Muscular Dystrophy
Muscular dystrophy most often results from defective and absent glycoproteins in the muscle membrane.[rx] Each type of muscular dystrophy caused by different gene deletions or mutations, causing various enzymatic or metabolic defects and disorders. [rx] The dystrophin gene is the largest in the human genome, with 79 exons in its structure.[rx] The dystrophin gene is factor to a high of spontaneous mutations because of its enormous size (>2 × 106 bases).[rx]
- Genes are like blueprints – they contain coded messages that determine a person’s characteristics or traits in their future life. They are arranged along 23 rod-like pairs of chromosomes, [rx] with one-half of each pair being inherited from each parent or forefather. Each half of a chromosome pair is similar to the other and except for one pair, which determines the sex of the individual.
- Autosomal dominant inheritance – occurs when a child receives a normal gene from one parent and a defective gene from the other parent to parent. Autosomal meaning the genetic mutation can occur on any of the 22 non-sex chromosomes in each of the body’s cells. Dominant means only one parent needs to pass along the abnormal gene in order to produce the disorder usually. In families where one parent carries a defective gene, each child has a 50 percent chance of inheriting the gene or therefore the disorder. Males and females may equally at risk and the severity of the disorder can differ from person to person.[rx]
- Autosomal recessive inheritance – It means that both parents must carry and pass on the faulty gene. The parents each have one defective gene but this is not affected by the disorder. Children in these families have a 25 percent chance of inheriting both coping of the defective gene and a 50 percent chance of inheriting one gene and therefore becoming a carrier, can pass along the defect to their children. Children of either sex can be affected by this pattern of inheritance. [rx]
- X-linked (or sex-linked) recessive inheritance – It may occur when a mother carries the affected gene on one of her two X chromosomes and passes it to her son mean males always inherit an X chromosome from their mother and a Y chromosome from their father, while daughters inherit an X chromosome from each parent). Sons of carrier mothers have a 50 percent chance of inheriting the disorder. Daughters also have a 50 percent chance of inheriting the defective gene but usually are not affected, since the healthy X chromosome they receive from their father can offset the faulty one received from their mother. Affected fathers cannot pass an X-linked disorder to their sons but their daughters will be carriers of that disorder. Carrier females occasionally can exhibit milder symptoms of MD [rx]
Modes of Inheritance
Autosomal Dominant, Autosomal Recessive, X-Linked – Emery-Dreifuss (EDMD)
Autosomal Dominant, Autosomal Recessive – Limb-Girdle (Dysferlinopathy, Erb), Pelvifemoral, Scapulohumeral, etc.
Autosomal Dominant – Facioscapulohumeral (Landouzy-Dejerine), Late-Onset Distal (>40 Years old), Myotonic, Oculopharyngeal, Scapuloperoneal, etc.
Autosomal Recessive – Congenital, Early Onset Distal (<40 years old)
X-Linked – Becker (Benign Pseudohypertrophic), Duchenne (pseudohypertrophic)
Autosomal Dominant, Autosomal Recessive, X-Linked Inheritance – Emery-Dreifuss (EDMD)
Autosomal Dominant, Autosomal Recessive Inheritance
- Limb-Girdle (Erb) Muscular Dystrophy – The majority are autosomal recessive but can be autosomal dominant.[rx] The age of onset is variable with the distribution of involved muscles to include limbs and trunk. May display a heterogeneous phenotype.[rx] The recessive form of the disease tends to have an earlier onset and progresses more quickly, whereas the dominant form follows a slower and more variable course.[rx]
Autosomal Dominant Inheritance
- Facioscapulohumeral (FSHD) Muscular Dystrophy – Caused by an autosomal dominant deletion of 3.3 kb repeat on chromosome 4.[rx] Approximately 95% of cases are due to a mutation in the D4Z4 region in FSHD1.[rx] Other areas, such as the SMCHD1 region in FSHD2, can also cause this disease.[rx]
- Myotonic Muscular Dystrophy – Myotonic muscular dystrophy (or simply Myotonic dystrophy) results from the impaired expression of the Dystrophia Myotonica Protein Kinase (DMPK).[rx] Caused by an autosomal dominant abnormally expanded CTG trinucleotide repeat sequence located in the 3′ untranslated region of the Dystrophia Myotonica Protein Kinase (DMPK) gene.[rx]
- Oculopharyngeal Muscular Dystrophy – Age of onset is approximately 30 to 40 years of age. The distribution of involved muscles includes the extraocular and pharyngeal muscles. Caused by an autosomal dominant GCG trinucleotide repeat resulting in deficient mRNA transfer from the nucleus.[rx]
Autosomal Recessive Inheritance
- Congenital Muscular Dystrophy – Caused by a mutation of the sarcolemmal protein Merosin gene, deficiencies or mutations in laminin-alpha 2, collagen type VI, integrin-alpha 7, and glycosyltransferases.[rx]
- Becker Muscular Dystrophy – Caused by a mutation of muscle protein dystrophin gene, which codes for the protein dystrophin, with 79 exons, by far the largest gene known in humans.[rx] This gene transmitted in an X-linked recessive manner.[rx] Its location is on the small arm (p) of the X chromosome at the Xp21 locus position.[rx] Without dystrophin, muscle cells deteriorate or die. The age of onset is 10 to 20 years old, with the distribution of involved muscles to be generalized.[rx]
- Duchenne Muscular Dystrophy – Caused by a mutation of the dystrophin gene, located on the small arm (p) of the X chromosome at the Xp21 position.[rx] A spontaneous mutation occurs in a third of cases.[rx][rx] X-linked recessive maternal-fetal transmission occurs in the other two-thirds of cases.[rx] The effect is resulting in a non-functional dystrophin protein, which causes similar effects as to that seen in Becker muscular dystrophy. Age of onset is approximately 3 to 5 years of age, with the distribution of involved muscles to be generalized.[rx]
Utilizing the following mnemonics will aid in the recall of the differential diagnoses associated with the weakness and ataxia of muscular dystrophy
Ataxia (Can’t Stand Very Well)
Ataxia, Acute (U.N.A.B.L.E. T.O. S.T.A.N.D.)
Underlying weakness (may mimic ataxia)
Nutritional neuropathy (vitamin B12 deficiency)
Other (rare metabolic or genetic diseases)
Stroke (ischemia or hemorrhage)
Toxins (drugs, toluene, mercury)
Demyelination (Miller Fisher, Guillain Barre, MS)
Ataxia, Chronic (C.A.N.T. S.T.A.N.D.)
Autosomal recessive ataxias
Nutritional (vitamin B12 deficiency)
Stroke (ischemia or hemorrhage)
Toxins (drugs, toluene, mercury)
Alcohol Intoxication/Autosomal dominant ataxia
Weakness, Acute (M.I.S.S. G.I.M.P)
Myelopathy (acute) / myopathy
Paralytic toxins/periodic paralysis
Weakness, Chronic (G, I.’ A.M. L.I.M.P, C.A.N.T. S.T.A.N.D.)
Iatrogenic (paralytic agents, aminoglycosides, steroids)
Lou Gehrig disease (ALS, motor neuron disease-usually gradual)
Infection (polio, botulism)
Periodic paralysis, porphyria, paraproteinemia
Neoplastic (meningitis, paraneoplastic)
Toxins (lead, arsenic, pufferfish, tick paralysis)
Acute/subacute, bilateral with minimal sensory involvement
Systemic illness (anemia)
Neuromuscular junction disease (Myasthenia, Lambert-Eaton syndrome)
Diseases Or Conditions Potentially Mistaken For This Disease
Acid maltase deficiency
Dermatomyositis sine dermatitis
Inclusion body myositis
Late-onset spinal muscular atrophy
McArdle’s deficiency (myophosphorylase deficiency)
Motor neuron disease
Diseases Or Conditions That Must Be Ruled Out
While muscular dystrophy is not a diagnosis of exclusion, it is often confused for several diseases due to their overlapping etiologies. The clinician must exclude the following diseases in a patient with a muscular disorder, which can otherwise cause significant morbidity and mortality:
Electrolyte imbalance: sodium, potassium, and magnesium
Postictal (Todd’s) paralysis
Symptoms of Muscular Dystrophy
The signs and symptoms consistent with muscular dystrophy are:[rx]
- Progressive muscular wasting
- Poor balance
- Scoliosis (curvature of the spine and the back)
- Progressive inability to walk
- Waddling gait
- Mild intellectual impairment
- Breathing difficulties
- Swallowing problems
- Lung and heart weakness
- Calf deformation
- Limited range of movement
- Respiratory difficulty
- Muscle spasms
- Gowers’ sign
- Chronic respiratory infections precipitated by weakness in the smooth muscle of the bronchioles.[rx]
- Impotence caused by gonadal atrophy, which is characteristically associated with myotonic dystrophy.[rx]
- It is common to possess dysphagia, which is esophageal muscle involvement.[rx]
- Myotonia is a term that describes the inability to relax muscles, which classically indicating as an inability to loosen one’s grip or release a handshake.[rx]
- As a pediatric disease, parents will often complain that their child is clumsy or becomes extremely weak quickly.[rx]
- The Gower sign is when subjects try to stand from a supine position, they march their hands and feet to each other).[rx]
- Weakness and stiffness of distal muscles are usually the presenting symptoms in adolescents with myotonic dystrophy.[rx]
Diagnosis of Muscular Dystrophy
- Arrhythmias – Cardiac arrhythmias are more significant in patients with muscular dystrophy. The typical electrocardiogram (ECG) most commonly shows increased net RS in lead V1; deep, narrow Q waves from the precordial leads, with tall right precordial R waves in V1.[rx] Cardiac disturbances may occur commonly in patients with Duchenne muscular dystrophy Type 1 (DM1).[rx] Myotonic dystrophy may affect the heart muscle, causing arrhythmias and heart block.[rx] ECG abnormalities include first-degree heart block with more extensive conduction system involvement. A complete heart block and sudden death may occur.[rx]
- Congestive Heart Failure – Congestive heart failure rarely occurs except with severe stress, such as pneumonia.[rx] Congestive heart failure occurs infrequently but may result from cor pulmonale secondary to acute or chronic respiratory failure disease.[rx] Mitral valve prolapse also occurs commonly.[rx]
- Dilated Cardiomyopathy – Genetic dilated cardiomyopathies account for nonischemic dilated cardiomyopathies.[rx] Some are associated with muscular dystrophy. In the skeletal myopathies, a dominant R wave in lead V1 (indicative of prominent with high posterior wall involvement, by the same mechanism as in posterior wall myocardial infarction).[rx] A cardiac cause of death is not always certain types the presence of cardiomyopathy in almost all patients.[rx] The incidence of cardiac involvement in Duchenne muscular dystrophy is as high as 95%.[rx] Chronic heart failure may occur in 50% of children.[rx]
- Contractures – Most patients have joint contractures of varying degrees at elbows, hips, knees, and ankles. Contractures that present at birth are referred to as arthrogryposis. Contractures of both the heel cords and iliotibial bands manifest by age six years when toe walking is associated with a lordotic posture, joint contractures, and limitations of hip flexion and extension of the knee, elbow, and wrist are made worse by prolonged sitting.[rx]
- Delayed Motor Milestones – Duchenne muscular dystrophy is usually identified in children at approximately three years of age when the parents have first seen slow motor development.[rx] Clinical symptoms often begin between 5 and 15 years of age.[rx] Sitting, standing, and walking are developmentally delayed, and the child is clumsy, falls frequently, and has difficulty climbing stairs.[rx]
- Expressionless Facies – The inability to close the eyes completely may be noted from early childhood. The face is expressionless, and the pouting of the lips makes whistling impossible. The muscular weakness and wasting produce a” drooping expression.” In myotonic dystrophy, the face is hatchet-shaped due to facial wasting and weakness, and there is bilateral partial ptosis.[rx]
- Fractures – Muscle weakness and inactivity, particularly once a person is in a wheelchair full time, lead to osteoporosis and pathologic fractures. If a fracture occurs, bisphosphonates may help to strengthen bone, although there are no long-term studies on safety in this population.[rx]
- Gait Instability – The boys stumble repeatedly and have trouble keeping up with friends when playing. Running, jumping, and hopping is always abnormal.[rx]
- Gower’s Sign – This clinical sign can be evoked by asking the child to stand from a sitting position.[rx] Children with muscular dystrophy and other disorders with muscle wasting will not possess the muscle force to stand.[rx] They may alternatively first move into a prone position, thrust themselves onto all fours, and suddenly “walk” their hands along their thighs to a standing posture.[rx] The appearance of a Gower sign signifies significant proximal muscle weakness. More specifically, it is caused by the weakness of the lumbar and gluteal muscles.[rx]
- Muscle Wasting – Muscular weakness always begins in the pelvic girdle, causing a “waddling” gait. [rx] Hypertrophy of the calf muscles is apparent in 80% of cases.[rx] The pattern of muscle wasting present in Becker muscular dystrophy bears a close resemblance to that seen in Duchenne disease. Proximal muscles, particularly of the lower extremities, are prominently involved. As the disease progresses, weakness becomes more generalized.[rx]
- Myotonia – TThe word myotonia applies to a prolonged unconscious muscle contraction demonstrated through not being able to loosen grasp. The patient may have a delay in releasing grip when shaking hands. A pause in opening and closing the fists is observable. Myotonia emerges typically at the age of 5 years and is demonstrable through percussion of the thenar eminence, jaw, and musculature of the forearm. [rx][rx]
- Pseudohypertrophy –Pseudohypertrophy of the muscle extends to the toes.[rx] Boys will exhibit, in preschool, with muscle weakness, trouble walking, and wide calves (pseudohypertrophy) caused by healthy muscle fiber replacement with fat and connective tissue.[rx] Although the calves are big, the muscle is small. Enlargement of muscles, particularly in the calves, is an early and prominent finding. Congenital can also have calf hypertrophy.[rx]
- Proximal Muscle Weakness – Proximal muscle weakness may be remarkably apparent when contrasted to distal weakness in many of the conditions listed.[rx] Specific evaluation for this, such as arising from a low seat or a squatting posture, is needed.[rx] This deterioration is succeeded with bilateral sternocleidomastoid and trapezius; myalgias without weakness; winging of the scapula; continuous muscle fiber loss leading to weakness principally of the voluntary muscles; proximal arms and legs. Congenital dystrophy forms may present with hypotonia plus proximal or generalized muscle weakness. Loss of muscle strength is progressive, with leg involvement more severe than arm involvement.
- Scoliosis – Once scoliosis begins, it is relentlessly progressive. Curves of more than 20 degrees require surgical intervention to maintain pulmonary function.[rx]
- Toe Walking – The foot assumes an equinovarus position, and the child tends to walk on the toes because of the weakness of the anterior tibial and peroneal muscles.[rx] Patients with muscular dystrophy often toe-walk because of the weakness of the anterior tibial and peroneal muscles, causing the feet to assume a talipes equinovarus position.[rx]
- Cognitive Dysfunction – Mild to moderate cognitive problems are common but not universal.[rx] Intellectual impairment in Duchenne dystrophy is common; the average intelligence quotient is approximately one standard deviation below the mean.[rx] A moderate degree of intellectual disability causes these children to have a mean IQ of approximately 80.[rx]
- Hypersomnia – The excessive urge to sleep and daytime somnolence is common.[rx]
- Seizures –In merosin and FKRP deficiency, only a small number of patients have mental retardation and seizures.[rx]
- Visual Disturbances – Ocular abnormalities due to eye muscle dysfunction lead to impaired vision.[rx] Myotonic dystrophy may present as difficulty in opening eyes after tight closure.[rx]
- Bladder Instability – Bladder functions are often mildly affected with urinary urgency as a frequent symptom.[rx]
- Cataracts – The affected individual may be referred from an ophthalmologist after a recent examination, which revealed the potential for an underlying disorder such as myotonic dystrophy (iridescent spots).[rx][rx]
- Frontal Baldness – This is characteristic of myotonic dystrophy, possibly due to gonadal atrophy and subsequent hypogonadism.[rx]
- Generalized Digestive Complaints – Smooth muscle dysfunction may cause megacolon, volvulus, cramping pain, and malabsorption in the gastrointestinal tract.[rx] Disturbed gastrointestinal peristalsis. Decreased esophageal and colonic motility.[rx] Palatal, pharyngeal, and tongue involvement produce dysarthric speech, nasal voice, and swallowing problems.[rx][rx]
- Gonadal Atrophy and Hypogonadism – Small soft testes suggesting atrophy are associated with myotonic dystrophy leading to hypogonadism.[rx][rx]
- Insulin Resistance – Diabetes is commonly associated with muscular dystrophy.[rx]
- Chest Deformity – The chest deformity with scoliosis impairs pulmonary function, which is already diminished by muscle weakness.[rx] Examine for gynecomastia, which can be present in patients with myotonic dystrophy.
- Recurrent Pulmonary Infections – By age 16 to 18 years, patients are predisposed to serious, sometimes fatal pulmonary infections.[rx] Susceptibility to respiratory tract infections and progressive deterioration of pulmonary function generally lead to premature death, usually into the twenties.[rx]
- Respiratory Insufficiency – Respiratory failure is the commonest cause of death.[rx] Inspection will identify the areas of muscle wasting. A patient presenting with rapid-onset muscle weakness requires an urgent full assessment, as respiratory muscle involvement may lead to respiratory failure.[rx] Some patients have a diaphragm and intercostal muscle weakness, resulting in respiratory insufficiency.[rx]
- Sleep Apnea – An increased need or desire for sleep is common, as is diminished motivation.[rx]
Blood and urine tests can detect defective genes and help identify specific neuromuscular disorders. For example:
- Creatine kinase – is an enzyme that leaks out of the damaged muscle. Elevated creatine kinase levels may indicate muscle damage, including some forms of MD before physical symptoms become apparent. Levels are significantly increased in the early stages of Duchenne and Becker MD. Testing can also determine if a young woman is a carrier of the disorder.[rx] The level of serum aldolase an enzyme involved in the breakdown of glucose, is measured to confirm a diagnosis of skeletal muscle disease. High levels of the enzyme, which is present in most body tissues, are noted in people with MD and some forms of myopathy. [rx]
- Myoglobin – is measured when injury or disease in skeletal muscle is suspected. Myoglobin is an oxygen-binding protein found in cardiac and skeletal muscle cells. High blood levels of myoglobin are found in people with MD.
- Polymerase chain reaction (PCR) – can detect some mutations in the dystrophin gene. Also known as molecular diagnosis or genetic testing, PCR is a method for generating and analyzing multiple copies of a fragment of DNA.
- Serum electrophoresis – is a test to determine quantities of various proteins in a person’s DNA. A blood sample is placed on specially treated paper and exposed to an electric current. The charge forces the different proteins to form bands that indicate the relative proportion of each protein fragment. [rx]
- Exercise tests – can detect elevated rates of certain chemicals following exercise and are used to determine the nature of the MD or other muscle disorders. Some exercise tests can be performed bedside while others are done at clinics or other sites using sophisticated equipment. These tests also assess muscle strength. They are performed when the person is relaxed and in the proper position to allow technicians to measure muscle function against gravity and detect even slight muscle weakness. If weakness in respiratory muscles is suspected, respiratory capacity may be measured by having the person take a deep breath and count slowly while exhaling.[rx]
- Genetic testing – looks for genes known to either cause or be associated with inherited muscle disease. DNA analysis and enzyme assays can confirm the diagnosis of certain neuromuscular diseases, including MD. Genetic linkage studies can identify whether a specific genetic marker on a chromosome and a disease are inherited together. They are particularly useful in studying families with members of different generations who are affected. An exact molecular diagnosis is necessary for some of the treatment strategies that are currently being developed. Advances in genetic testing include whole-exome and whole-genome sequencing, which will enable people to have all of their genes screened at once for disease-causing mutations, rather than have just one gene or several genes tested at a time. Exome sequencing looks at the part of the individual’s genetic material, or genome, that “code for” (or translate) into proteins. [rx]
- Genetic counseling – can help parents who have a family history of MD determine if they are carrying one of the mutated genes that cause the disorder. Two tests can be used to help expectant parents find out if their child is affected.
- Amniocentesis – done usually at 14-16 weeks of pregnancy, tests a sample of the amniotic fluid in the womb for genetic defects (the fluid and the fetus have the same DNA). Under local anesthesia, a thin needle is inserted through the woman’s abdomen and into the womb. About 20 milliliters of fluid (roughly 4 teaspoons) is withdrawn and sent to a lab for evaluation. Test results often take 1-2 weeks.
- Chorionic villus sampling, or CVS – involves the removal and testing of a very small sample of the placenta during early pregnancy. The sample, which contains the same DNA as the fetus, is removed by a catheter or a fine needle inserted through the cervix or by a fine needle inserted through the abdomen. The tissue is tested for genetic changes identified in an affected family member. Results are usually available within 2 weeks. [rx]
- Alanine Aminotransferase (ALT, SGPT) – The normal range in males is 10 to 40 U/L. The normal range in females is 8 to 35 U/L; it is elevated in muscular dystrophy.[rx]
- Aldolase (Serum) – The normal range is 0 to 6 U/L. It is elevated in muscular dystrophy but decreases in later stages of muscular dystrophy.[rx]
- Arterial Blood Gases (ABG) – Normal ranges: PO2 is 75 to 100 mmHg; PCO2 is 35 to 45 mm Hg; HCO3- is 24 to 28 mEq/L; pH is 7.35 to 7.45. Respiratory acidosis can develop if there are defects in muscles involved in respiration.[rx]
- Aspartate Aminotransferase (AST) – Normal ranges from 0 to 35 U/L. Elevated in muscular dystrophy.[rx]
- Creatine Kinase (CK, CPK) and Creatine Kinase Isoenzymes (CK-MB and CK-MM) – Normal ranges from 0 to 130 U/L. Elevated in muscular dystrophy (hyperkalemia).[rx] The serum enzymes, especially creatine phosphokinase (CPK), is increased to more than ten times normal, even in infancy and before the onset of weakness.[rx][rx] Serum CK levels are invariably elevated between 20 and 100 times normal in Duchenne muscular dystrophy.[rx] The levels are abnormal at birth, but values decline late in the disease because of inactivity and loss of muscle mass.[rx] Elevated CPK levels at birth are diagnostic indicators of Duchenne muscular dystrophy.[rx]
- Lactate Dehydrogenase (LDH) – Normal ranges from 50 to 150 U/L. Elevated in muscular dystrophy. LDH 4: 3 to 10%, LDH 5: 2 to 9%.[rx]
- Urinalysis (UA) – Glucose in urine is commonly associated with muscular dystrophy due to the high incidence of diabetes mellitus within this population.[rx] Myoglobinuria may also be present.[rx]
- Magnetic Resonance Imaging (MRI) – Coronal T1 weighted MRI may confirm the nonuniform fatty atrophy.[rx] There will be a relatively normal sartorius. Lateral radiographs may show cavus foot deformity and diffuse osteopenia.[rx] The sagittal view will show diffuse fat replacement of the gastrocnemius & semimembranosus muscles. These changes contribute to the prominent calves typical of affected children.[rx]
- Computerized Tomography (CT) – Axial CT shows denervation hypertrophy of the tensor fascia lata. The muscle becomes enlarged with an increase in intramuscular fat.
- Chromosomal Analysis – DNA testing for common mutations and chromosomal analysis can now rule out Down syndrome, myotonic dystrophy, and other disorders. In both Becker and Duchenne dystrophies, the DNA deletion size does not predict clinical severity.[rx] [rx]
- Electrocardiogram (ECG) – Often, patients will have annual echocardiograms to stay ahead of any developing cardiomyopathy. This study will demonstrate atrial and atrioventricular rhythm disturbances. The typical electrocardiogram shows an increased net RS in lead V1; deep, narrow Q waves in the precordial leads.[rx] A QRS complex too narrow to be right bundle branch block; and tall right precordial R waves in V1.[rx] Dominant R wave in lead V1 is the best clue to the actual diagnosis.[rx] Normal PR interval, QRS duration.
- Electromyography (EMG) – Allows assessment for denervation of muscle, myopathies, and myotonic dystrophy, motor neuron disease. EMG demonstrates features typical of myopathy.[rx] Clinical examination, electromyography changes are found in almost any muscle: waxing and waning of potentials termed the dive bomber effect.[rx]
- Genetic Testing – A definitive diagnosis of muscular dystrophy can be established with mutation analysis on peripheral blood leukocytes.[rx] Genetic testing demonstrates deletions or duplications of the dystrophin gene in 65% of patients with Becker dystrophy, which is approximately the same percentage as in Duchenne dystrophy.[rx] [rx]
- Immunocytochemistry – A definitive diagnosis of muscular dystrophy can be established based on dystrophin deficiency in a biopsy of muscle tissue.[rx] Also, staining of muscle with dystrophin antibodies can demonstrate the absence or deficiency of dystrophin localizing to the sarcolemmal membrane.[rx] DIsease carriers may demonstrate a mosaic pattern, but dystrophin analysis of muscle biopsy specimens for carrier detection is not reliable.[rx]
- Immunofluorescence testing – can detect specific proteins such as dystrophin within muscle fibers. Following the biopsy, fluorescent markers are used to stain the sample that has the protein of interest.
- Electron microscopy – can identify changes in subcellular components of muscle fibers. Electron microscopy can also identify changes that characterize cell death, mutations in muscle cell mitochondria, and an increase in connective tissue seen in muscle diseases such as MD. Changes in muscle fibers that are evident in a rare form of distal MD can be seen using an electron microscope.[rx]
- Nerve conduction velocity test – measure the speed and strength with which an electrical signal travels along a nerve. A small surface electrode stimulates a nerve, and a recording electrode detects the resulting electrical signal either elsewhere on the same nerve or on a muscle controlled by that nerve. The response can be assessed to determine whether nerve damage is present. Repetitive stimulation studies involve electrically stimulating a motor nerve several times in a row to assess the function of the neuromuscular junction. The recording electrode is placed on a muscle controlled by the stimulated nerve, as is done for a routine motor nerve conduction study.[rx]
- Muscle Biopsy – The muscle biopsy shows muscle fibers of varying sizes as well as small groups of necrotic and regenerating fibers. Connective tissue and fat replace lost muscle fibers. Muscle biopsy usually shows nonspecific dystrophic features, although cases associated with FHL1 mutations have features of myofibrillar myopathy.[rx] Muscle biopsy shows muscle atrophy involving Type 1 fibers selectively in 50 percent of cases.[rx]\
- Polysomnogram – Excessive daytime somnolence with or without sleep apnea is not uncommon. Sleep studies, noninvasive respiratory support (biphasic positive airway pressure [BiPAP]), and treatment with modafinil may be beneficial.[rx]
- Slit Lamp – An examination for cataracts that may be present in patients with muscular dystrophy.[rx]
- Western Blot – A diagnosis of Duchenne dystrophy can also be made by Western blot analysis of muscle biopsy specimens, revealing abnormalities on the quantity and molecular weight of dystrophin protein. On Western blot, Becker muscular dystrophy individuals dystrophin levels will appear normal, although the protein itself is abnormal; this is in comparison to Duchenne muscular dystrophy affected individuals who have a significantly decreased dystrophin on Western blot.[rx]
- Assisted ventilation – is often needed to treat respiratory muscle weakness that accompanies many forms of MD, especially in the later stages. Air that includes supplemental oxygen is fed through a flexible mask (or, in some cases, a tube inserted through the esophagus and into the lungs) to help the lungs inflate fully. Since respiratory difficulty may be most extreme at night, some individuals may need overnight ventilation. Many people prefer non-invasive ventilation, in which a mask worn over the face is connected by a tube to a machine that generates intermittent bursts of forced air that may include supplemental oxygen. Some people with Duchenne MD, especially those who are overweight, may develop obstructive sleep apnea and require nighttime ventilation. Individuals on a ventilator may also require the use of a gastric feeding tube.
- Supportive Bracing – This helps to maintain normal function as long as possible proper wheelchair seating is essential. Molded ankle-foot orthoses help stabilize gait in patients with foot drop.[rx] Lightweight plastic ankle-foot orthoses (AFOs) for footdrop are extremely helpful. Footdrop is easily treatable with AFOs.[rx] Bracing may be performed for function; for example, dorsiflexion of the feet with ankle-foot orthotics to prevent tripping or to provide support and comfort.[rx]
- Supportive Counseling – Some forms of muscular dystrophy may be arrested for prolonged periods, and most patients remain active with a normal life expectancy.[rx] Thus, vocational training and supportive counseling are important to provide the information necessary to plan their future.
- Genetic Counseling — Genetic counseling is recommended.[rx] With X-linked inheritance, male siblings of an affected child have a 50% chance of being affected, and female siblings have a 50% chance of being carriers. If the affected individual marries and has children, all daughters will be carriers of this X-linked recessive disorder. Genetic counseling should be offered to the mother, female siblings, offspring, and any maternal relatives.
- Cell-based therapy – The muscle cells of people with MD often lack a critical protein, such as dystrophin in Duchenne MD or sarcoglycan in some of the limb-girdle MDs. Scientists are exploring the possibility that the missing protein can be replaced by introducing muscle stem cells capable of making the missing protein in new muscle cells. Such new cells would be protected from the progressive degeneration characteristic of MD and potentially restore muscle function in affected persons.
- Gene replacement therapy – Gene therapy has the potential for directly addressing the primary cause of MD by providing for the production of the missing protein. Hurdles to be overcome include determining the timing of the therapy (to possibly overcome the genetic defect), avoiding or easing potential immune responses to the replacement gene, and, in the case of Duchenne MD, the large size of the gene to be replaced. For those MDs with central nervous system consequences (congenital muscular dystrophy and myotonic dystrophy), researchers are developing and fine-tuning gene therapy vectors (a way to deliver genetic materials to cells) that can cross the protective blood-brain barrier.
Treatment may include physical therapy, respiratory therapy, speech therapy, orthopedic appliances used for support, and corrective orthopedic surgery. Treatment includes supportive physiotherapy to prevent contractures and prolong ambulation.[rx] Maintaining function in unaffected muscle groups for as long as possible is the primary goal. Although activity fosters maintenance of muscle function, strenuous exercise may hasten the breakdown of muscle fibers.[rx]
- Physical therapy can help prevent deformities, improve movement, and keep muscles as flexible and strong as possible. Options include passive stretching, postural correction, and exercise. A program is developed to meet the individual’s needs. Therapy should begin as soon as possible following diagnosis before there is joint or muscle tightness.
- Passive stretching can increase joint flexibility – and prevent contractures that restrict movement and cause loss of function. When done correctly, passive stretching is not painful. The therapist or other trained health professional slowly moves the joint as far as possible and maintains the position for about 30 seconds. The movement is repeated several times during the session. Passive stretching on children may be easier following a warm bath or shower. [rx]
- Regular, moderate exercise -can help people with MD maintain range of motion and muscle strength, prevent muscle atrophy, and delay the development of contractures. Individuals with a weakened diaphragm can learn coughing and deep breathing exercises that are designed to keep the lungs fully expanded.
- Postural correction – is used to counter the muscle weakness, contractures, and spinal irregularities that force individuals with MD into uncomfortable positions. When possible, individuals should sit upright, with feet at a 90-degree angle to the floor. Pillows and foam wedges can help keep the person upright, distribute weight evenly, and cause the legs to straighten. Armrests should be at the proper height to provide support and prevent leaning.
- Support aids – such as wheelchairs, splints and braces, other orthopedic appliances, and overhead bed bars (trapezes) can help maintain mobility. Braces are used to help stretch muscles and provide support while keeping the person ambulatory. Spinal supports can help delay scoliosis. Night splints, when used in conjunction with passive stretching, can delay contractures. Orthotic devices such as standing frames and swivel walkers help people remain standing or walking for as long as possible, which promotes better circulation and improves calcium retention in bones. [rx]
- Repeated low-frequency bursts of electrical stimulation – to the thigh muscles may produce a slight increase in strength in some boys with Duchenne MD, though this therapy has not been proven to be effective. [rx]
- Occupational therapy – may help some people deal with progressive weakness and loss of mobility. Some individuals may need to learn new job skills or new ways to perform tasks while other persons may need to change jobs. Assistive technology may include modifications to home and workplace settings and the use of motorized wheelchairs, wheelchair accessories, and adaptive utensils.[rx]
- Speech therapy – may help individuals whose facial and throat muscles have weakened. Individuals can learn to use special communication devices, such as a computer with a voice synthesizer.[rx]
- Dietary changes – have not been shown to slow the progression of MD. Proper nutrition is essential, however, for overall health. Limited mobility or inactivity resulting from muscle weakness can contribute to obesity, dehydration, and constipation. A high-fiber, high-protein, low-calorie diet combined with recommended fluid intake may help. Feeding techniques can help people with MD who have a swallowing disorder and find it difficult to pass from or liquid from the mouth to the stomach. [rx]
There is no specific treatment to stop or reverse any form of MD. The U.S. Food and Drug Administration (FDA) has approved injections of the drugs golodirsen and viltolarsen to treat Duchenne muscular dystrophy (DMD) patients who have a confirmed mutation of the dystrophin gene that is amenable to exon 53 skipping.
- Anti-Arrhythmics – The pharmacological treatment of patients with a prevalent involvement of the cardiac tissue conduction relies on the use of ACE-inhibitors and appropriate antiarrhythmic drugs. In the case of atrial arrhythmias, the preference is for drugs such as antiarrhythmics (flecainide, propafenone) and beta-blockers. [rx]
- Anti-Epileptics – Children need to be followed closely by neurologists. Management of epilepsy is necessary for some patients.[rx]
- Anti-Myotonics – The pain associated with muscle rigidity is greatly alarming in the patient.[rx] When myotonia is disabling, treatment with a sodium channel blocker such as phenytoin (100 mg orally three times daily), procainamide (0.5–1 g orally four times daily), or mexiletine (150 to 200 mg orally three times daily) may prove helpful, but the associated side effects, particularly for antiarrhythmic medications, are often limiting.[rx]
- Non-Steroidal Anti-Inflammatory Drugs – Treatment involves the administration of non-steroidal anti-inflammatory drugs to decrease pain and inflammation.[rx]
- Steroids –Glucocorticoids, administered as prednisone in a dose of 0.75 mg/kg per day, significantly slow progression of muscular dystrophy for up to 3 years.[rx] Some patients cannot tolerate glucocorticoid therapy; weight gain and increased risk of fractures, in particular, represent a significant deterrent.[rx] There is recent evidence that oral steroids early in the disease can lead to dramatically improved outcomes.[rx]
- Golodirsen (SRP-4053) – This drug is an antisense therapy used for the treatment of Duchenne muscular dystrophy. Patients need to have a confirmed mutation of the dystrophin gene to facilitate exon 53 skipping. It is FDA approved, but the evidence to support its use is not yet well established.[rx][rx]
- Contracture Release – Surgical release of contracture deformities is used to maintain normal function as long as possible.[rx] Massage and heat treatments also may be helpful.
- Defibrillator or Cardiac Pacemaker – Cardiac function requires monitoring, and pacemaker placement may be a consideration if there is evidence of heart block.[rx] Individuals with either Emery-Dreifuss or myotonic dystrophy may require a pacemaker at some point to treat cardiac problems. Management of cardiomyopathy and arrhythmias may be life-saving.[rx] In patients with severe syncope, established conduction system disorders with second-degree heart block previously documented, or tri-fascicular conduction abnormalities with significant PR interval lengthening, consideration needs to be given towards placement of a cardiac pacemaker.[rx] An advanced cardiac block is also an indication to install a pacemaker.[rx]
- Shoulder Surgery – Individuals with facioscapulohumeral muscular dystrophy may benefit from surgery to stabilize the shoulder.
- Spinal Correction – Scoliotic surgery is an option when curves exceed 20 degrees to prolong respiratory function or walking ability or both.[rx]
- Tendon or muscle-release surgery – is recommended when a contracture becomes severe enough to lock a joint or greatly impair movement. The procedure, which involves lengthening a tendon or muscle to free movement, is usually performed under general anesthesia. Rehabilitation includes the use of braces and physical therapy to strengthen muscles and maintain the restored range of motion. A period of immobility is often needed after these orthopedic procedures, thus the benefits of the procedure should be weighed against the risk of this period of immobility, as the latter may lead to a setback.
- Surgery to reduce the pain and postural imbalance – caused by scoliosis may help some individuals. Scoliosis occurs when the muscles that support the spine begin to weaken and can no longer keep the spine straight. The spinal curve, if too great, can interfere with breathing and posture, causing pain. One or more metal rods may need to be attached to the spine to increase strength and improve posture. Another option is spinal fusion, in which bone is inserted between the vertebrae in the spine and allowed to grow, fusing the vertebrae together to increase spinal stability.
- Cataract surgery – involves removing the cloudy lens to improve the person’s ability to see.