Other Neuromuscular Disorders

Other Neuromuscular Disorders

George H. Thompson

Frank R. Berenson

Neuromuscular disorders other than cerebral palsy and myelodysplasia are less common; however, patients with these disorders do present in pediatric orthopaedic and neuromuscular clinics. These disorders include the muscular dystrophies and congenital myopathies, spinal muscular atrophy, Friedreich ataxia, hereditary motor sensory neuropathies (HMSN), and poliomyelitis. It is important that an accurate diagnosis be established so that an effective treatment program can be planned and initiated. Delaying the diagnosis of these disorders may lead to inappropriate treatment; furthermore, the mother of an affected child might have further pregnancies and give birth to another child with the genetic disorder (1). Accurate diagnosis requires a careful evaluation of history, physical examination, and appropriate diagnostic studies (2).


The history should include the details of pregnancy, delivery, and growth and development of the child involved. Questions should be asked regarding in utero activity, complications of delivery, birth weight, Apgar score, problems during the neonatal period, age at achievement of developmental motor milestones, age at onset of the current symptoms, and information that will clarify whether the condition is static or progressive. Systemic symptoms, such as cardiac disease, cataracts, seizures, or other abnormalities, should also be ascertained.

The family history is important in diagnosis because these disorders, with the exception of poliomyelitis, are genetic in origin. In order to arrive at an accurate diagnosis, family members of the child or adolescent involved may need to be examined for subtle expressions of the same disorder and may also be required to undergo hematologic or other studies.


Most children who present for evaluation of a suspected neuromuscular disorder usually have one or more of the following: a delay in developmental milestones, abnormal gait, foot deformity, or spinal deformity. There is usually a history of progression. Physical examination consists of a thorough musculoskeletal and neurologic evaluation. Observing the child walking and performing simple tasks, such as rising from a sitting position on the floor, can be useful. Observation of the gait may reveal decreased arm swing, circumduction of the legs, scissoring, or short cadence. Standing posture may reveal increased lumbar lordosis or a wide base position for balance. Also, in the standing position, the appearance of the feet should be observed. Pes cavus or cavovarus deformities are common physical findings in many of these disorders. Having the child walk on the heels and toes gives a gross assessment of motor strength, and having the child run may reveal an increase in muscle tone or ataxia. There is an increased incidence of scoliosis in patients with neuromuscular disorders (3, 4).

Inspection of the skin should be performed for evidence of skin rashes or other abnormalities. Typical facies of the patient with spinal muscular atrophy and congenital myotonic dystrophy should become familiar to orthopaedic surgeons. The tongue should be examined to detect evidence of fasciculation suggestive of anterior horn cell diseases. Excessive drooling is common in both cerebral palsy and congenital myotonic dystrophy. In the latter, nasal speech may also be present. A thorough ophthalmologic examination is necessary in order to elicit external ophthalmoplegia or retinitis pigmentosa. In myotonic dystrophy, cataracts may develop during adolescence.

Muscle testing should be carefully performed. Generally, myopathic disorders selectively affect proximal limb muscles before affecting distal muscles. Early in the disease process, the muscles demonstrate proportionally greater weakness than
would be expected from the degree of atrophy. The converse is true in neuropathies.

A careful neurologic evaluation usually completes the musculoskeletal examination. Sensory responses must be checked individually and recorded. Decreased vibratory sensation may be present in HMSNs such as Charcot-Marie-Tooth disease. In spinal muscular atrophy, the deep-tendon reflexes may be absent, but in cerebral palsy, they are increased. A positive Babinski sign confirms upper motor neuron disease. Abnormalities in the Romberg test and rapid alternating movements may indicate cerebellar involvement. Mental function evaluation may be necessary, because organic mental deterioration may be part of some neurologic syndromes. In many cases, the assistance of a pediatric neurologist can be invaluable in performing a careful neurologic and mental evaluation, because minor subtleties may offer clues to diagnosis.


Appropriate diagnostic studies are imperative for the accurate diagnosis of myopathic and neuropathic disorders (5, 6). These can be divided into hematologic studies, electromyography (EMG) with nerve conduction studies and needle electrode exam, muscle biopsy, and nerve biopsy. Molecular diagnostic studies have become available for many of these disorders, including Duchenne and Becker muscular dystrophies, myotonic dystrophy, the hereditary sensory motor neuropathies, and spinal muscular atrophy.

Hematologic Studies.

The measurement of serum creatine phosphokinase (CPK) is the most sensitive test for demonstrating abnormalities of striated muscle function. The level of elevation parallels the rate and amount of muscle necrosis and decreases with time as the muscle is replaced by fat and fibrous tissue. The highest CPK levels are typically seen in the earliest stages of Duchenne or Becker muscular dystrophy, in which increases of 20 to 200 times the normal values may be found (6). The level of elevation of CPK does not correlate with the severity or rate of progression of the disorder. The highest levels are usually found in Duchenne muscular dystrophy. Umbilical cord blood CPK levels should be obtained in all male infants who are suspected of having this disorder (7). Birth trauma may elevate the CPK in umbilical cord blood, but in the healthy child, this elevation disappears promptly, whereas the enzyme level remains elevated in muscular dystrophy. Serum CPK may be mildly or moderately elevated in other dystrophic disorders, such as facioscapulohumeral muscular dystrophy and Emery-Dreifuss muscular dystrophy. It is also mildly elevated in female carriers of Duchenne muscular dystrophy, although they are asymptomatic. In congenital myopathies and peripheral neuropathies, the CPK levels are usually normal or only mildly elevated. In other neuromuscular disorders that do not directly affect striated muscle, the CPK levels are normal. Serum enzymes, such as aldolase and serum glutamic oxaloacetic transaminase (SGOT), are also important in the study of striated muscle function. Aldolase levels correlate well with the CPK levels.


EMG can differentiate between a myopathic and a neuropathic process but is rarely helpful in establishing a definitive diagnosis. Characteristics of neuropathic disorders include the presence of fibrillation potentials, increased insertional activity, and high-amplitude, increased-duration motor unit potentials (6). The fibrillation potential represents denervated individual muscle fibers firing spontaneously.

The EMG in myopathy is characterized by low-voltage, short-duration polyphasic motor unit potentials (6). Myopathies rarely demonstrate EMG changes characteristic of a neuropathy, although in an inflammatory muscle disease with significant muscle breakdown, there may be prominent fibrillations. The use of an experienced electromyographer is imperative in the accurate performance of the test and interpretation of EMG data.

Nerve Conduction Studies.

Nerve conduction studies are important in the establishment of the diagnosis of peripheral neuropathy in children. Nerve conduction velocities are normal in children with anterior horn cell diseases, nerve root diseases, and myopathies. The normal value in the child older than 5 years is 45 to 65 m per second. In infants and younger children, the velocity is lower because myelination is incomplete.

Motor conduction velocity may be slowed in HMSN (e.g., Charcot-Marie-Tooth disease) before clinical deficits are present. The nerve conduction studies can help determine whether the neuropathy involves an isolated nerve or is a disseminated process.

Muscle Biopsy.

Historically, muscle biopsy has been the most important test in determining the diagnosis of a neuromuscular disorder. More recently, molecular genetic testing has become equally, if not more, important. Muscle biopsy material is usually examined by routine histology, special histochemical stains, and electron microscopy. The criterion for selecting the muscle for biopsy is clinical evidence of muscle weakness. Muscles that are involved but are still functioning are selected in chronic diseases, such as Duchenne muscular dystrophy, because they demonstrate the greatest diagnostic changes. A more severely involved muscle may be chosen in an acute illness because the process has not had sufficient time to progress to extensive destruction. In patients who have proximal lower extremity muscle weakness, biopsy of the vastus lateralis is performed, whereas in those with distal weakness, a biopsy of the gastrocnemius is performed. Biopsy of the deltoid, biceps, or triceps is performed for shoulder girdle or proximal upper extremity weakness.

Muscle biopsies can be performed as an open procedure (8) or by percutaneous needle (9). The biopsies are obtained under general anesthesia, spinal anesthesia, regional nerve block, or a field block surrounding the area of incision. It is important that local anesthetic not be infiltrated into the biopsied muscle, because this may alter the morphology of the muscle. The vastus
lateralis is the most common muscle chosen. A 4-cm incision is made and the underlying fascia is incised longitudinally. The muscle is directly visualized in order to avoid including normal fibrous septae in the specimens. Muscle clamps are used for obtaining three specimens. The clamps are oriented in the direction of the muscle fibers. A 2- to 3-mm piece of muscle is grasped in each end of the clamp. The muscle is cut at the outside edge of each clamp and a cylinder of muscle is excised. The use of a muscle clamp helps keep the muscle at its resting length and minimizes artifact. One specimen is quickly frozen in liquid nitrogen (-160°C) to prevent loss of soluble enzymes. This specimen is used for light microscopy with a variety of special preparations. The other specimens are used for routine histology and electron microscopy. The wound is subsequently closed in layers. Electrocautery may be used during the closure. If it is used before the biopsy, it may inadvertently damage the specimens and alter the morphology.

Nerve Biopsy.

Occasionally, biopsy of a peripheral nerve is helpful in demyelinating disorders. Usually, the sural nerve is selected for biopsy because of its distal location and lack of autogenous zone of innervation. The patient notices no sensory change or only a mild sensory diminution after excision of the 3-to 4-cm segment of the nerve. Hurley et al. (8) reported a single incision for combined muscle and sural nerve biopsy. An incision over the posterolateral aspect of the calf allows access to the nerve and either the soleus or the peroneal muscle. This avoids the necessity for making two incisions. This technique was demonstrated to be useful in disorders in which both a muscle and a nerve biopsy may be necessary for arriving at a diagnosis.

Other Studies.

Other studies that may be helpful in establishing the diagnosis of a neuromuscular disorder include electrocardiogram (ECG), pulmonary function studies, magnetic resonance imaging (MRI), ophthalmologic evaluation, amniocentesis, and pediatric neurology evaluation.

Duchenne muscular dystrophy, Friedreich ataxia, and myotonic dystrophy demonstrate ECG abnormalities. Duchenne muscular dystrophy is frequently associated with mitral valve prolapse secondary to papillary muscle involvement (10, 11). Arrhythmias under anesthesia have been reported with both Duchenne and Emery-Dreifuss muscular dystrophies (12, 13).

Pulmonary function studies demonstrate involvement of respiratory muscles, but they do not establish the diagnosis. If respiratory muscle involvement is present, the rate of deterioration can be followed up with periodic studies. This is important if surgery is contemplated in children or adolescents with muscular dystrophy, spinal muscular atrophy, or Friedreich ataxia. The forced vital capacity (FVC) is the most important study after arterial blood gas measurements (14).

MRI has been demonstrated to distinguish muscles affected by neuropathic disorders from those affected by myopathic disorders (15). Imaging estimates of the disease severity by degree of muscle involvement correlate well with clinical staging. MRI may also be important in selecting appropriate muscles for biopsy.

Ophthalmologic evaluation may demonstrate subtle or more obvious ocular changes associated with specific disorders.


Genetic research through molecular biologic techniques has tremendously enhanced our understanding of the genetic aspects of many of these disorders (16, 17). The determination of the exact location of chromosomal and gene defects has led to the possibility of genetic engineering being used to correct these disorders. Unfortunately, genetic testing is quite costly, and for many disorders, such testing is not commercially available. Also, a negative test does not necessarily exclude certain disorders. For this reason, the decision to carry out genetic testing should be made only by a neuromuscular specialist or geneticist. In each of the various disorders, the current status of genetic and molecular biology research is discussed in this chapter.


The muscular dystrophies are a group of noninflammatory inherited disorders with a progressive degeneration and weakness of skeletal muscle that has no apparent cause in the peripheral or the central nervous system (CNS). These have been categorized according to clinical distribution, severity of muscle weakness, and pattern of genetic inheritance (Table 16-1). An accurate diagnosis is important, both for prognosis and management of the individual patient and for identification of genetic factors that may be crucial in planning for subsequent children by the family involved.


Duchenne Muscular Dystrophy.

Duchenne muscular dystrophy is the most common form of muscular dystrophy (18).

TABLE 16-1 Classification of Muscular — Dystrophies

Sex-linked muscular dystrophy




Autosomal recessive muscular dystrophy


Infantile facioscapulohumeral

Autosomal dominant muscular dystrophy





Transmission is by an X-linked recessive trait. A single gene defect is found in the short arm of the × chromosome. The disease is characterized by its occurrence exclusively in the male sex, except for rare cases associated with Turner syndrome. In this rare event, the XO karyotype who carries the defective gene may demonstrate the phenotype found in male patients with the disorder (6). This disorder is associated with a high mutation rate, and a positive family history is present in approximately 65% of the cases. Duchenne muscular dystrophy occurs in approximately 1 in 3500 live male births, with about one-third of the children involved having acquired the disease because of a new mutation.

Becker muscular dystrophy is a similar, but less common and less severe form of muscular dystrophy. It occurs in approximately 1 in 30,000 live male births, becomes apparent later in childhood, and has a more protracted and variable course than Duchenne muscular dystrophy. This disorder is discussed later but is mentioned here because of the similar inheritance pattern and molecular biology abnormality.

Clinical Features.

Duchenne muscular dystrophy is generally clinically evident when the child is at an age of between 3 and 6 years. Earlier onset may also occur. The family may have observed that the child’s ability to achieve independent ambulation was delayed or that he has become a toe walker. Children at the age of 3 years or older may demonstrate frequent episodes of tripping and falling, in addition to difficulty in activities requiring reciprocal motion, such as running or climbing stairs. Inability to hop and jump normally is commonly present.

FIGURE 16-1. A: A 7-year-old boy with Duchenne muscular dystrophy demonstrates precarious stance due to mild hip abduction contractures. Observe the pseudohypertrophy of the calves. B: Posterior view demonstrates mild ankle equinus in addition to the calf pseudohypertrophy. C: Side view shows an anterior tilt to the pelvis and increased lumbar lordosis, and the head and the shoulders are aligned posterior to the pelvis. This characteristic posture maintains the weight line posterior to the pelvis and center of gravity, compensates for the muscle weakness, and helps maintain balance.

In Duchenne muscular dystrophy, there is progressive weakness in the proximal muscle groups that descend symmetrically in both lower extremities, particularly the gluteus maximus, gluteus medius, quadriceps, and tibialis anterior muscles. The abdominal muscles are involved. Involvement of the shoulder girdle muscles (i.e., trapezius, deltoid, and pectoralis major muscles) and lower facial muscles occurs later. Pseudohypertrophy of the calf muscles caused by the accumulation of fat is common but not invariably present. Most patients have cardiac involvement, most commonly a sinus tachycardia and right ventricular hypertrophy. Life-threatening dysrhythmia or heart failure ultimately develops in approximately 10% of patients. Many also have a static encephalopathy, with mild or moderate mental retardation (19). Death from pulmonary failure and occasionally from cardiac failure occurs during the second or third decades of life.

During gait the child’s cadence is slow, and he or she develops compensatory changes in gait and stance as weakness progresses. Sutherland et al. (20, 21) documented disease progression by measuring the gait variables of cadence, swing phase, ankle dorsiflexion, and anterior pelvic tilt. The hip extensors, primarily the gluteus maximus, are the first muscle group to be involved. Initially, the patient compensates by carrying the head and shoulders behind the pelvis, maintaining the weight line posterior to the hip joint and center of gravity (Fig. 16-1). This produces an anterior pelvic tilt and increases
lumbar lordosis. Cadence and swing-phase ankle dorsiflexion decrease, and the patient develops a waddling, wide-based gait with shoulder sway to compensate for gluteus medius weakness. Muscle weakness requires that the force line remains behind the hip joint and in front of the knee joint throughout single limb support (20, 21 and 22), and hip abductors and quadriceps muscles force the patient to circumduct during the swing phase of gait while at the same time shifting the weight directly over the hip joint. The generalized pelvic weakness requires considerable forward motion to be generated by the spine for the patient to advance. Ankle plantar flexion becomes fixed, and the stance phase is reduced to the forefoot, resulting in even more difficulty with balance and cadence. Foot inversion develops as peroneal strength diminishes. The tibialis posterior muscle, which is one of the last muscles to be involved, is responsible for the inversion or varus deformity of the foot.

Weakness in the shoulder girdle, which occurs 3 to 5 years later, precludes the use of crutches to aid in ambulation. It also makes it difficult to lift the patient from under the arms. This tendency for the child to slip a truncal grasp has been termed Meyeron sign. As the weakness in the upper extremities increases, the child becomes unable to move his or her arms. Although the hands retain strength longer than the arms, use of the hands is limited because of weakness of the arms.

Clinical diagnosis of Duchenne muscular dystrophy is established by physical examination, including gait and specific muscle weakness, and by the absence of sensory deficits. The upper extremity and knee deep-tendon reflexes are lost early in the disease, whereas the ankle reflexes remain positive until the terminal phase. A valuable clinical sign is the Gower sign. The patient is placed prone or in the sitting position on the floor and asked to rise. This is usually difficult, and the patient may require the use of a chair for assistance. The patient is then asked to use his or her hands to grasp the lower legs and force the knees into extension. The patient then walks his or her hands up the lower extremities to compensate for the weakness in the quadriceps and gluteus maximus. This sign may also be found in congenital myopathies and spinal muscular atrophy. The contracture of the iliotibial band can be measured by the Ober test. To perform this test, the child is placed on his or her side with both hips flexed. The superior leg is then abducted and extended and allowed to fall into adduction. The degree of abduction contracture can be measured by the number of degrees the leg lacks in coming to the neutral position. Tendo-Achilles contractures also occur. Contracture of the tendo-Achilles and the iliotibial band are the most consistent deformities noted during the physical examination.

Duchenne muscular dystrophy progresses slowly but continuously. A rapid deterioration may be noted after immobilization in bed, even for short periods after respiratory infections or, perhaps, extremity fractures. Every effort should be made to maintain a daily ambulatory program. In the absence of treatment, children are usually unable to ambulate effectively by the age of 10 years (5, 23, 24 and 25). The chief cause is loss of strength in the hip extensors and ankle dorsiflexors (26). These two factors can be used as a guide to predict when ambulation will cease. With loss of standing ability, the child becomes wheelchair dependent. This results in a loss of the accentuated lumbar lordosis that protected the child from kyphoscoliosis (27). As a consequence, most patients subsequently develop a progressive spinal deformity.

Myocardial deterioration is also a constant finding. ECG changes are present in more than 90% of children with Duchenne muscular dystrophy. The average intelligence quotient of these patients has been shown to be approximately 80 (19).

Hematologic Studies.

The serum CPK is markedly elevated in the early stages of Duchenne muscular dystrophy. This may be 200 to 300 times the normal value, but decreases as the disease progresses and muscle mass is reduced. CPK levels are also elevated in female carriers of the disease (two to three times the normal value for women and girls), although not to the same extent as in affected boys. There is an 80% consistency in the results when the CPK test is repeated at three consecutive monthly intervals (28). Aldolase and SGOT levels may also be elevated, but the elevations are not unique to striated muscle disease.


Although EMG will support the diagnosis of a myopathy, if the clinical findings and CPK are both suggestive of a muscular dystrophy, this test is typically not necessary. EMG shows characteristic myopathic changes with reduced amplitude, short duration, and polyphasic motor action potentials (6).

Muscle Biopsy.

The muscle biopsy specimen reveals degeneration with subsequent loss of fiber, variation in fiber size, proliferation of connective tissue and, subsequently, of adipose tissue as well (6). Increased cellularity is present, with occasional internal migration of the sarcolemmal nuclei. Histochemical testing reveals loss of clear-cut subdivisions of fiber types, especially with adenosine triphosphatase reaction, and a tendency toward type I fiber predominance. In the past, this was the diagnostic procedure of choice. However, the standard today is to first obtain blood samples for DNA polymerase chain reaction (PCR) testing for dystrophinopathies. If this is positive, there is no need for a muscle biopsy. If PCR testing is negative, then muscle biopsy is indicated for arriving at a definitive diagnosis.

Genetic and Molecular Biology Studies.

A single gene defect in the short arm of the × chromosome has been identified as being responsible for both Duchenne and Becker muscular dystrophies (16, 17, 29, 30). The status of genetic and molecular biology in Duchenne muscular dystrophy has been summarized by Shapiro and Specht (6). The gene is located at the Xp21.2 region and spans 2 million base pairs (31, 32). It includes 65 exons (i.e., coding regions) and encodes the 400-kDa protein dystrophin. The large size of the gene correlates with the high rate of spontaneous mutation. Dystrophin is a component of cell membrane cytoskeleton and represents 0.01% of skeletal muscle protein. Its distribution within
skeletal, smooth, and cardiac muscle and within the brain correlates well with the clinical features in Duchenne and Becker muscular dystrophies. A structural role for the dystrophin protein is suggested by studies that demonstrate concentration of the protein in a lattice organization in the cytoplasmic membrane of skeletal muscle fibers (33, 34). Demonstrable mutations, deletions, or duplications of dystrophin are found in 70% to 80% of the affected male patients (31, 32, 35, 36). The reading frame hypothesis distinguishes the mutations that correlate with the more severe Duchenne muscular dystrophy from those that correlate with the less severe Becker muscular dystrophy. Mutations that disrupt the translational reading frame or the promoter (i.e., the specific DNA sequence that signals where RNA synthesis should begin) result in a presumably unstable protein, and this correlates with Duchenne muscular dystrophy. In contrast, mutations that do not disrupt the translational reading frame or the promoter have a lower molecular weight and semifunctional dystrophin. This correlates with the less severe Becker muscular dystrophy (31, 37).

Dystrophin testing (by dystrophin immunoblotting), DNA mutation analysis (by PCR or DNA Southern blot analysis), or both, provide methods of differentiating between Duchenne and Becker muscular dystrophies on the one hand, and other initially similar disorders [such as dermatomyositis, limb-girdle muscular dystrophy (LGMD), Emery-Dreifuss muscular dystrophy, and congenital muscular dystrophy] on the other (36, 38, 39). In the latter disorders, the dystrophin is normal. In patients with Duchenne muscular dystrophy, there is a complete absence of dystrophin, whereas in Becker muscular dystrophy, dystrophin is present, but is altered in size, decreased in amount, or both. Nicholson et al. (40) reported a positive relation between the amount of dystrophin and the age at loss of independent ambulation in 30 patients with Duchenne muscular dystrophy and in 6 patients with Becker muscular dystrophy. The researchers found that even low concentrations of dystrophin in Duchenne muscular dystrophy may have functional significance and may explain the variability of age at which ambulation ceases. The presence of partially functional dystrophin protein is sufficient to minimize the phenotypic expression, leading to the milder disorder of Becker muscular dystrophy (31, 35, 38). The same tests can be used to improve detection of female carriers (36, 39). On the basis of smaller-than-normal dystrophin protein, two atypical forms of Becker muscular dystrophy have been recognized. These are myalgia without weakness in male patients (similar to metabolic myopathy), and cardiomyopathy with little or no weakness in male patients (41).

Research studies are investigating the possibility of dystrophin replacement in diseased muscles. This involves the implantation of myoblasts, or muscle precursor cells, into the muscles of patients with Duchenne muscular dystrophy (42). This has been successful in producing dystrophin in the murine mdx model of Duchenne muscular dystrophy (43). Unfortunately, the results in human male patients have been disappointing (44, 45, 46, 47 and 48). Perhaps the most promising evolving treatment for Duchenne’s is the genetic technique of “exon skipping” or splice modulation, where there is modulation of dystrophin premessenger RNA splicing, enabling functional dystrophin protein to be produced (49).

Medication Treatments.

A number of medications have been tried to improve strength and function and prolong time to disability in Duchenne dystrophy. Steroids, such as prednisone and deflazacort, have been shown to preserve or improve strength, prolong ambulation, and slow the progression of scoliosis (50, 51, 52, 53, 54, 55, 56, 57, 58 and 59). Thus, this has become a mainstay of therapy in many neuromuscular clinics. Unfortunately, the side effects-weight gain, osteoporosis with vertebral fractures, and myopathy-limit their usefulness (37, 52, 53 and 54, 56, 60). Alternate day therapy, or pulse therapy with steroid treatment on the first 10 days of each month, may limit the side effects, slow deterioration of muscle function and not impact on patient quality of life (61, 62). Although prednisone and deflazacort appear to be equally efficacious, deflazacort appears to cause fewer side effects, especially related to weight gain (63). Creatinine supplementation has been evaluated and demonstrated an increase in handgrip strength and fat-free mass, but no improvement in functional tasks or activities of daily living (64). It did demonstrate a significant improvement in resistance to fatigue (65). Perhaps more promising is treatment with extended release albuterol, which has demonstrated increase in lean body mass, decrease in fat mass, and improved functional measures in short-term treatment of dystrophinopathy patients (66, 67). Azathioprine has also been evaluated in Duchenne muscular dystrophy but has not shown beneficial effects (68). Aminoglycoside therapy with intravenous gentamicin administration has been studied in two trials (69, 70). A decrease in serum CPK levels was demonstrated, but there was no effect on muscle strength.

Gene therapy for muscular dystrophies has proven difficult, primarily because of the size of the viral vectors and also because of the complications of immune reactions that may occur. Therefore, gene therapy is still very much in the early investigational stages. This treatment has been reviewed in detail by Chamberlain (71). Dystrophin delivery to muscle has been attempted with four primary vectors: adenovirus, retroviruses, adeno-associated viruses, and plasmids. Complications of this technology included triggering of a cellular immune response, poor integration of the vector into the host gene, and lack of a sustained response, to name only a few (72). Stem cell therapy may be a promising intervention for the dystrophinopathies. In the mdx mouse, bone marrow transplantation and injection of normal muscle-derived stem cells led to partial restoration of dystrophin expression (73).

Genetic and Psychological Counseling.

Proper diagnosis and early genetic counseling may help prevent the birth of additional male infants with Duchenne muscular dystrophy. It must be remembered that approximately 20% of families have already conceived and delivered a second affected male infant before the diagnosis is made in the first (78, 158). Genetic counseling with parents and family groups is important in the management of psychological problems arising when the genetic nature of the diagnosis becomes known.

Becker Muscular Dystrophy.

Becker muscular dys trophy is similar to Duchenne muscular dystrophy in clinical appearance and distribution of weakness, but it is less severe (159, 160). Onset is generally after the age of 7 years and the rate of progression is slower. The patients usually remain ambulatory until adolescence or the early adult years. The Gower maneuver may occur as the weakness progresses (Fig. 16-3). Pseudohypertrophy of the calf is common, and eventually equinus and cavus foot deformities develop (Fig. 16-4). Cardiac involvement is frequent. There may be a family history of atypical muscular dystrophy. Pulmonary problems are less severe and the patient’s life expectancy is greater.

Emery-Dreifuss Muscular Dystrophy.

Emery Dreifuss muscular dystrophy is an uncommon sex-linked recessive disorder characterized by early contractures and cardiomyopathy (12). The typical phenotype is seen only in the male sex, although milder or partial phenotypes have been reported in female carriers (163, 164, 165 and 166). Affected boys show mild muscle weakness in the first 10 years of life and a tendency for toe walking. The Gower maneuver may be present in young children. The distinctive clinical criteria occur in late childhood or early adolescence. These include tendo-Achilles contractures, elbowflexion contractures, neck-extension contracture, tightness of the lumbar paravertebral muscles, and cardiac abnormalities involving brachycardia and first-degree, and eventually complete, heart block (165, 167). The muscle weakness is slowly progressive, but there may be some stabilization in adulthood.

FIGURE 16-3. A: A 13-year-old boy with suspected Becker muscular dystrophy uses the Gower maneuver to stand from a sitting position. B: Manually assisted knee extension is necessary to achieve upright stance. C: Front view.

FIGURE 16-4. A: Pseudohypertrophy of the calves in an 18-year-old man with Becker muscular dystrophy. He is a brace-free ambulator. B: Posterior view.

Most patients are able to ambulate into the fifth and sixth decades of life. Obesity and untreated equinus contractures can lead to the loss of ambulatory ability at an earlier age (6).

The CPK level in patients with Emery-Dreifuss muscular dystrophy is only mildly or moderately elevated. EMG and muscle biopsy reveal myopathy. The diagnosis of this form of muscular dystrophy should be considered in patients with a myopathic phenotype, after Duchenne and Becker muscular dystrophies have been ruled out (usually by testing for dystrophin) (6). The condition should also be distinguished from scapuloperoneal muscular dystrophy and the rigid spine syndrome (167).

Genetic and Molecular Biology Studies.

The gene locus for the most common variant of Emery-Dreifuss muscular dystrophy, the X-linked recessive form, has been localized, in linkage studies, to the long arm of the × chromosome at Xq28 (168, 169 and 170). Rarely, an autosomal dominant form and, even less frequently, an autosomal recessive form may be seen. The autosomal dominant and autosomal recessive forms have an identified gene mutation on the lamin A/C gene on chromosome 1q21 (170). The specific type of gene testing depends on the family history and sex of the affected individual.

Jul 21, 2016 | Posted by in ORTHOPEDIC | Comments Off on Other Neuromuscular Disorders

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