Distal Myopathy with Rimmed Vacuoles (DMRV)/Distal muscular dystrophies are a group of rare, genetic, inherited primary muscle disorders showing progressive weakness and atrophy preferentially in the hands, forearm, lower legs, or feet. The distal muscles are those farther from the center of the body and include the muscles of the lower arms and legs and the hands and feet. Conversely, the proximal muscles are the muscles closest to the center of the body such as the muscles of the shoulder, pelvis, and upper arms and legs. Extensive progress in understanding the molecular genetic background has changed the classification and extended the list of confirmed entities to almost 20 different disorders, making the differential diagnostic procedure both easier and more difficult. Distal phenotypes first have to be differentiated from neurogenic disorders. The axonal form of Charcot–Marie–Tooth disease with late-onset distal weakness and distal forms of chronic spinal muscular atrophy may mimic those of the distal dystrophies. Increasing numbers of reports suggest increasing awareness of distal phenotypes in muscular dystrophy. DD usually appears between ages 40 and 60. But it can sometimes show up as early as the teenage years. DD affects both men and women.
Synonyms of Distal Myopathy
- Distal Muscular Dystrophy
- Welander’s distal myopathy,
- Finnish (tibial) distal myopathy,
- Miyoshi distal myopathy,
- Nonaka distal myopathy,
- Gowers–Laing distal myopathy,
- Hereditary inclusion-body myositis type 1,
- Distal myopathy with vocal cord and pharyngeal weakness, and
- ZASP-related myopathy
Subdivisions of Distal Myopathy
- Distal Myopathy 3 (MPD3)
- Distal Myopathy with Rimmed Vacuoles (DMRV)
- Distal Myopathy with Vocal Cord and Pharyngeal Signs
- Inclusion Body Myopathy Type 2 (IBM2)
- Laing Distal Myopathy
- Laing Early-Onset Distal Myopathy
- Miyoshi Myopathy
- Nonaka Myopathy
- Tibial Distal Myopathy
- Udd Distal Myopathy
- Welander Distal Myopathy
Causes of Distal Muscular Dystrophies
All forms of DD are caused by changes (mutations) in certain genes. Changes in several different genes can cause different types of DD.
Muscles are made up of bundles of long muscle fibers (muscle cells). These fibers contract when nerve signals from the brain go to the specific spot (junction) where the nerve activates the muscle. In some cases, the mutations that cause DD are in genes that make certain molecules within muscle cells.
The genes in your body usually occur in pairs. You inherit a copy from each parent. A change in only 1 copy of the gene is enough to cause most forms of DD. This means the disease passes down in a dominant manner. In some other types of DD, the disease occurs only if you have changes in both copies of the gene. These recessive forms of DD include Nonaka distal myopathy and Miyoshi muscular dystrophy. In Finnish distal myopathy, people with 1 copy of the changed gene have a weakness in the muscles in the fronts of the lower legs (the tibial muscles) after age 40. People with Finnish DD who inherit 2 changed genes have muscle problems in childhood. They may need a wheelchair by age 30
The cause of this dystrophy is very hard to determine because it can be a mutation in any of at least eight genes and not all are known yet. These mutations can be inherited from one parent, autosomal dominant, or from both parents, autosomal recessive. Along with being able to inherit the mutated gene, distal muscular dystrophy has slow progress therefore the patient may not know that they have it until they are in their late 40s or 50s. There are eight known types of distal muscular dystrophy. All of these affect different regions of the extremities and can show up as early as 5 years of age to as late as 50 years old.
Because the genetic defects that cause DD are usually passed on through families (hereditary), you have a higher risk for DD if the condition runs in your family. Some forms of DD are much more common in certain groups. For example, Nonaka distal myopathy most commonly appears in people of Japanese descent. Finnish (tibial) distal myopathy happens more often in people of Finnish descent.
Symptoms of Distal Muscular Dystrophies
Typically, the first symptom of distal muscular dystrophy (DD) is weakness in the distal muscles — those farthest away from the hips and shoulders such as those in the hands, feet, lower arms or lower legs. With time, other muscle groups may become affected as well.
- Distal myopathy with vocal cord and throat (pharyngeal) weakness affects the hands, legs, and voice. It may cause difficulty swallowing. It usually happens between ages 35 and 60.
- Finnish (tibial) distal myopathy affects the legs, particularly the muscles near the shin. It usually shows up after age 40, and most people with this DD can still walk throughout their life. People who inherit 2 copies of the defective gene may have more severe weakness beginning in childhood. They may not be able to walk later. Their heart may also be affected.
- Hereditary inclusion-body myopathy type 2 shows up between ages 25 and 40. It usually weakens the foot and thigh.
- Miyoshi distal myopathy causes weakness that begins in the calf muscles. It shows up between ages 15 and 30. Some people with this form of DD may eventually be unable to walk.
- Nonaka distal myopathy affects the muscles near the shin first. It then affects muscle groups in the upper arm, upper leg, and neck. The thigh muscle (quadriceps) usually stays healthy.
- Welander distal myopathy usually affects the arms first and then the legs. It shows up in people between ages 40 and 50.
- Clinical presentation is diverse and can range from asymptomatic electrical myotonia to severe weakness and disability, including cardiac conduction defects, infertility, cataracts, and insulin resistance.[rx]
- Other signs and symptoms of myotonic dystrophy include clouding of the lens of the eye (cataracts) and abnormalities of the electrical signals that control the heartbeat (cardiac conduction defects).
- MD includes hypotonia and muscle weakness typically presenting from birth to early infancy, poor or decreased motor abilities, delay or arrest of gross motor development, joint and/or spinal deformities.
- Feeding difficulties, joint contractures, spinal deformities, respiratory compromise, and cardiac involvement.
- Joint contractures of shoulders, elbows, knees, and Achilles tendons often with associated prominent distal joint laxity but long finger flexor stiffness.
- Muscle weakness, gradually increasing difficulty with walking
- Severe upper extremity muscle weakness[rx]
- Toe-walking[rx]
- Use of Gower’s Maneuver to get up from floor[rx]
- Difficulty breathing[rx]
- Skeletal deformities of the chest, and back (scoliosis)[rx]
- Pseudohypertrophy of calf muscles[rx]
- Muscle cramps[rx]
- Heart muscle problems[rx]
- Elevated creatine kinase levels in blood[rx]
- Waddling gait
- Mild intellectual impairment
- Breathing difficulties
- Swallowing problems
- Lung and heart weakness
- Calf deformation
- Limited range of movement
- Respiratory difficulty
- Cardiomyopathy
- 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]
Or
- Abnormal, sometimes waddling, walk
- Joints that are fixed in a contracted position (late in the disease)
- Large and muscular-looking calves (pseudohypertrophy), which are not actually strong
- Loss of muscle mass, thinning of certain body parts
- Low back pain
- Palpitations or passing-out spells
- Shoulder weakness
- Weakness of the muscles in the face (later in the disease)
- Weakness in the muscles of the lower legs, feet, lower arms, and hands (later in the disease)
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Proximal muscle weakness (pelvic and/or shoulder girdle) with early-onset (age <12 years), adult-onset, or late-onset (age >30 years)
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Symmetric atrophy and wasting of proximal limb and trunk muscles; calf hypertrophy is rarely and sometimes only transiently present [Fardeau et al 1996].
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Scapular winging, scoliosis, Achilles tendon contracture, and other joint contractures (including hip, knee, elbow, finger, and spine)
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Waddling gait; tip-toe walking; difficulty in running, climbing stairs, lifting weights, and getting up from the floor or from a chair
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Sparing of facial, ocular, tongue, and neck muscles
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Elevated creatine kinase (CK) concentrations, especially in childhood or adolescence, with or without overt muscle symptoms
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Absence of cardiomyopathy and intellectual disability
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Back pain and myalgia; present in 50% of individuals with dominantly inherited calpainopathy [Vissing et al 2016]
Diagnosis of Distal Muscular Dystrophies
History and Physical
It includes detailed birth history, medical/surgical history, and 3-generation family history. Clinical features associated with myotonic dystrophy are as follow:[rx]
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Prenatal – polyhydramnios, reduced fetal movements, preterm delivery <36 weeks, small for gestational age.
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Neonatal – hypotonia, hyporeflexia, muscle weakness (distal > proximal), neck muscle weakness (flexion), myopathic facies (ptosis, facial diplegia, atrophy of temporalis muscles, tent-shaped mouth), contractures, arthrogryposis, scoliosis, talipes equinovarus, visual impairment (cataract, lens opacification), respiratory distress, weak cough, sleep apnea, pulmonary hypoplasia, bronchopulmonary dysplasia, raised right hemidiaphragm, pneumothorax, recurrent infections/otitis media, aspiration pneumonia, feeding and sucking difficulties, gastroparesis, GERD, constipation/diarrhea, fecal incontinence, increased sensitivity to anesthesia (due to respiratory muscle compromise and central dysregulation of breathing), cardiac conduction disturbances, valve defects (mitral), and early death.
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Infancy and childhood, age 1 to 10 years – usually, they are able to walk with improvement in motor function; however, progressive weakness restarts in the 2nd decade. Myotonia (by 10 years of age), intellectual disability (50-60%), autism, ADHD, psychiatric disorders, vision problems (hyperopia, astigmatism, cataract), excessive daytime sleepiness, cardiac and endocrine complications.
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Respiratory – respiratory difficulties are found in 50% of neonates and are the main cause of neonatal mortality and used to distinguish between mild and severe CDM.
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Musculoskeletal – proximal muscle weakness in DM1 indicates a poor prognosis. The biphasic course in myotonic dystrophy shows improved/stable disease until adolescence/young adult with gradual deterioration. Complications of muscle weakness may include scoliosis and contractures producing foot deformity and toe walking. Bulbar muscle weakness may produce swallowing, speech, and language difficulties.
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Cognition – Cognitive impairment is one of the most common and challenging manifestations of childhood DM1. CDM patients are most affected, with IQ range 40 to 80, mean 70 (average normal 100). Cognitive impairment correlates with the severity of weakness, size of CTG repeat, and maternal transmission.
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Sleep – excessive sleep disorder and sleep apnea may adversely affect learning, memory, high-level cognitive processing, and physical functioning, exacerbating psychomotor and cognitive delays.
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Psychosocial – 50% of children have psychiatric diseases (phobia, depression, anxiety), and ADHD. Avoidant personality, apathy, and autistic features may be present.
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Cancer – There is an increased risk of cancer in patients with type 1 myotonic dystrophy, including thyroid, uterine, choroidal melanoma, colon, testicular, prostate, and basal cell cancer.
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Other – features of adult “classic” myotonic dystrophy are not evident in childhood, including cataracts, significant cardiac disorders, and diabetes mellitus. Lens pathology is evident in 40% and can predict future cataracts. Conduction disturbances observed on ECG, or valve abnormalities may be symptomatic. Hypothyroidism, hypogonadism, growth hormone abnormalities, and androgen insensitivity are rare. In contrast, testicular atrophy and infertility are common in CDM males, as are irregular menses in CDM females.
Physical Exam
- Vital signs, weight, height, and head circumference measurements are essential. Comprehensive neonatal exam looking for dysmorphic features, contractures, scoliosis, pulmonary and cardiac evaluation for abnormal chest rise, or murmurs.
- Abdominal exam for organomegaly, back for scoliosis, the musculoskeletal system for contractures, detailed neurological exam assessing mental status, cranial nerves (myopathic facies, ptosis, dysphagia, weak cry/cough/gag, respiratory failure), motor (axial and appendicular hypotonia, frog-like posture, decreased movements), reflexes, Babinski response, sensory, coordination and primitive reflexes.
- Examine mother (myopathic facies, shake hand as myotonia prevents the prompt release of grip, percussion with a reflex hammer, by tapping thenar, wrist extensor will produce involuntary muscle contraction with a delay in relaxation, called percussion myotonia).[rx]
Laboratory Tests
When myotonic dystrophy is suspected after history and examination, creatinine kinase level followed by dystrophin gene deletion analysis or muscle biopsy with dystrophin antibody staining is the mainstay of the laboratory studies to confirm the diagnosis.[rx] However, in most instances, muscle biopsy is avoided, and genetic testing is confirmatory.
- Blood and urine tests – can detect defective genes and help identify specific neuromuscular disorders. On microscopic examination, the hallmark of congenital muscular dystrophy is ongoing myofiber necrosis and regeneration. Active muscle fiber necrosis and a cluster of basophilic regenerating fibers are more prominent at a younger age. In contrast, myofiber splitting with necrosis, increased internal nuclei, fiber hypertrophy, fatty replacement, and endomysia fibrosis are conspicuous in older age.[rx][rx]
- Creatine kinase – is an enzyme that leaks out of the damaged muscle. Elevated creatine kinase levels may indicate muscle damage, including some forms of congenital muscular dystrophy before physical symptoms become apparent. A creatine kinase level (CK), aldolase, alanine aminotransferase (ALT), and aspartate aminotransferase (AST), nerve conduction studies and EMG should be considered. However, creatine kinase levels may vary from being completely normal to significantly elevated based on phenotype. An elevated CK, aldolase level, usually signifies a dystrophic process.
- 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 congenital muscular dystrophy.
- 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 congenital muscular dystrophy 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 congenital muscular dystrophy. 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]
- Molecular Genetic Testing (first line) – targeted analysis of the DMPK gene appears positive for a heterozygous pathogenic variant in nearly 100% of affected individuals. If the diagnosis is uncertain, the panel can be completed. The multigene panel can include testing for the DMPK CTG repeat expansion and other disorders of interest, depending on the laboratory.
- Genetic counseling – can help parents who have a family history of congenital muscular dystrophy/ myotonic dystrophy 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 and congenital 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]
- Liver function tests – for transaminases, pulmonary function tests, and spinal radiographs to follow the progression of scoliosis are also important but less important. Elevations in the hepatobiliary enzymes alkaline phosphatase, gamma-glutamyl transferase (GGT), serum aspartate aminotransferase, and serum alanine aminotransferase can be seen. Elevations do not correlate with the severity of muscle weakness, disease duration, or serum levels of creatine kinase.[rx]
Radiographic Tests
- 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.[rx]
- Brain MRI – may show ventricular dilatation, cortical atrophy, hypoplasia of the corpus callosum, and white matter abnormalities.[rx][rx][rx][rx]
Other Tests
- 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, and congenital muscular dystrophy, 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]
- Electrodiagnostic (EDX) testing – has been the modality of choice for diagnosis prior to molecular testing. It has the capability to diagnose patients who are clinically asymptomatic or have subtle findings.[rx] Motor nerve conduction studies (NCS) show decreased amplitude with normal latency and normal conduction velocities. Sensory nerve conduction studies are typically normal. Electromyography (EMG) typically has normal insertional activity. Early recruitment with short duration and small amplitudes motor unit potentials are observed. Myotonic discharges are highly specific and consist of spontaneous discharges that have a waxing and waning of amplitude and frequency, typically from around 150/second to 20/second.[rx][rx] It is shown that evaluating distal muscles is more sensitive for detecting myotonic discharges than proximal muscles.[rx]
- Congenital 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, and congenital muscular 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 congenital muscular dystrophy. Changes in muscle fibers that are evident in a rare form of distal congenital muscular dystrophy 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]
- DNA banking Test – is the storage of DNA (typically extracted from white blood cells) for possible future use. Because it is likely that testing methodology and our understanding of genes, allelic variants, and diseases will improve in the future, consideration should be given to banking the DNA of affected individuals.
- 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 in 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]
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Muscle histopathology – shows nonspecific myopathic or dystrophic changes, including variation in fiber size, increase in internal nuclei, increase in endomysial connective tissue, and necrotic fibers. Electron microscopy may reveal specific alterations in nuclear architecture [rx]. Inflammatory changes may also be found in LMNA-related myopathies including EDMD [rx]. Muscle biopsy is now rarely performed for diagnostic purposes because of the lack of specificity of the dystrophic changes observed.
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Immunodetection of emerin – In normal individuals, the protein emerin is ubiquitously expressed on the nuclear membrane. Emerin can be detected by immunofluorescence and/or by western blot in various tissues: exfoliative buccal cells, lymphocytes, lymphoblastoid cell lines, skin biopsy, or muscle biopsy [rx].
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In individuals with XL-EDMD, emerin is absent in 95% [rx].
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In female carriers of XL-EDMD, emerin is absent in varying proportions in nuclei, as demonstrated by immunofluorescence. However, the western blot is not reliable in carrier detection because it may show either a normal or a reduced amount of emerin, depending on the proportion of nuclei expressing emerin.
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In individuals with AD-EDMD, emerin is normally expressed.
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Immunodetection of FHL1 – In controls, the three FHL1 isoforms (A, B, and C) are ubiquitously expressed in the cytoplasm as well as in the nucleus. The isoforms can be detected by immunofluorescence and/or western blot in fresh muscle biopsy or myoblasts, fibroblasts, and cardiomyocytes [rx].
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In individuals with FHL1-related XL-EDMD, FHL1 is absent or significantly decreased [rx].
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In female carriers of FHL1-related XL-EDMD, FHL1 is expected to be variably expressed.
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- Immunodetection of lamins A/C – Lamins A/C are expressed at the nuclear rim (i.e., nuclear membrane) and within the nucleoplasm (i.e., nuclear matrix). Depending on the antibody used, lamins A/C can be localized to both the nuclear membrane and matrix or to the nuclear matrix only. However, this test is not reliable for confirmation of the diagnosis of AD-EDMD because in AD-EDMD lamins A/C is always present due to the expression of the wild-type allele at the nuclear membrane and in the nuclear matrix. Western blot analysis for lamin A/C may contribute to the diagnosis, but yields normal results in many affected individuals[rx].
- Radionuclide angiography – using MUGA (multi–gated acquisition) scan reveals the deteriorating ventricular function with reduction of the left ventricular ejection fraction followed by reduction of the right ventricle ejection fraction.
- Heart muscle biopsies – (taken from 2 individuals) showed increased interstitial fibrosis compatible with dilated cardiomyopathy [rx]. Oxidative staining was normal without focal oxidative defects or significant disarray of the cardiomyocyte structure, in contrast to the classic observation in hypertrophic cardiomyopathy.
- Heterozygotes – In contrast to individuals with heterozygous pathogenic variants in TTN associated with add distal myopathy, the heterozygous parents of individuals with Salih myopathy remain asymptomatic with no cardiac or muscle disorder
Treatment of Distal Muscular Dystrophies
Clinicians should refer patients with muscular dystrophy to a clinic that has access to multiple specialties (e.g., physical therapy, occupational therapy, respiratory therapy, speech and swallowing therapy, cardiology, pulmonology, orthopedics, and genetics) designed specifically to care for patients with muscular dystrophy and other neuromuscular disorders in order to provide efficient and effective long-term care
Non-Pharmacological treatment
- Assisted ventilation – is often needed to treat respiratory muscle weakness that accompanies many forms of myotonic dystrophy, 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 myotonic dystrophy/congenital muscular dystrophy, 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/ myotonic 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 congenital muscular dystrophy often lack a critical protein, such as dystrophin in congenital muscular dystrophy, myotonic dystrophy, or sarcoglycan in some of the limb-girdle myotonic dystrophy. 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 congenital muscular dystrophy and potentially restore muscle function in affected persons.
- Gene replacement therapy – Gene therapy has the potential for directly addressing the primary cause of congenital muscular dystrophy 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 myotonic dystrophy the large size of the gene to be replaced. For that myotonic dystrophy 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.
- Myoblast transplantation – A case series evaluating myoblast transplantation into the tibialis anterior in 3 male participants with BMD pretreated with cyclosporine A provided insufficient evidence to determine the efficacy of myoblast transfer in BMD.
- Neutralizing antibody to myostatin – A phase 1 randomized controlled study of a neutralizing antibody (MYO-029) to an endogenous inhibitor of muscle growth (myostatin) performed in 116 participants with different types of muscular dystrophies provided evidence that MYO-029 is probably safe and tolerable in patients with BMD, LGMD2A–E, and LGMD2I. The study was not designed to assess the efficacy or long-term safety.
- Growth hormone for BMD – A randomized study evaluating the effects of subcutaneous growth hormone (sGH) in 10 patients with BMD provided insufficient evidence to support or refute the use of sGH to improve cardiac and pulmonary function in patients with BMD.
- Hand training program in Welander distal myopathy – A case series of a hand training program in 12 patients with Welander distal myopathy provided insufficient evidence to support or refute the benefit of the exercise program.
- Endurance training – Two case series studying the effect of endurance training in 9 ambulatory patients with LGMD2I and 11 men with BMD provided insufficient evidence to determine the benefit of endurance training to improve maximal oxygen uptake, maximal workload, and other patient-reported outcomes.
- Strength training and aerobic exercise training – The evidence base regarding the effectiveness of rehabilitation management of muscular dystrophies is limited. However, the available evidence suggests that this population would benefit from strengthening and aerobic fitness training programs. Due to the muscle degeneration in muscular dystrophy, there may be some risk of exercise-induced muscle damage, myoglobinuria, and subsequent overwork weakness following supramaximal, high-intensity exercise. There have been several randomized or quasirandomized controlled trials comparing strength training programs, aerobic exercise programs, or both to non-training controls in patients with a variety of neuromuscular disorders
- Nutrition – Patients with muscular dystrophy may have difficulty receiving adequate oral intake due to dysphagia or the inability to feed themselves due to arm weakness. Maintaining adequate nutrition and body weight is important for optimizing strength, function, and quality of life. When oral intake is inadequate, other means of maintaining intake (e.g., gastrostomy or jejunostomy feeding tubes) may be needed to maintain optimal nutrition. There is evidence from related conditions (amyotrophic lateral sclerosis [ALS]) that maintenance of nutrition and body weight prolongs survival.
Supportive Physiotherapy
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 congenital muscular dystrophy 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 congenital muscular dystrophy 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 congenital muscular dystrophy, 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 congenital muscular dystrophy. 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 congenital muscular dystrophy who have a swallowing disorder and find it difficult to pass from or liquid from the mouth to the stomach. [rx]
Medication
There is no specific treatment to stop or reverse any form of congenital muscular dystrophy. 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]
- Endocrine Management – In case of impaired growth and delayed puberty, advice from endocrinologists plays a crucial role in the development of the child.[rx] Progressive scoliosis and contracture require surgical intervention to prolong ambulation.[rx]
- Corticosteroid – deflazacort at a dose of 0.9mg/kg/day has been the mainstay of treatment.[rx][rx][rx] Corticosteroids should be started before physical disability and continue even after the loss of ambulation and in more severe cases.[rx] It is beneficial for improving pulmonary function, delays scoliosis (decreases the need for surgery), delaying the onset of cardiomyopathy, and prolongs survival.[rx][rx] Corticosteroid dose should be reduced by 25% to 33% in case of side effects.[rx]
- Nitric oxide – has become the drug of treatment in some cases to increase the blood supply to muscles through vasodilation.
- Non-Steroidal Anti-Inflammatory Drugs – Treatment involves the administration of non-steroidal anti-inflammatory drugs to decrease pain and inflammation.[rx]
- 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]
Medication should not be used
Avoidance of specific agents, including
- Inhaled sedation (halothane),
- IV sedation (thiopentone),
- Muscle relaxants (succinylcholine, vecuronium),
- Neostigmine, and
- Some chemotherapy is essential.
- Propofol-induced pain can induce myotonia.[rx]
Surgical Treatment
- 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.[rx]
- 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.
- Tracheostomy – and assisted ventilation are needed for patients with respiratory failure, and treatment of cardiomyopathy with ACE inhibitors and beta-blockers can help prolong survival.[rx]
- Cataract surgery – involves removing the cloudy lens to improve the person’s ability to see.
Novel Therapies
-
Antisense Oligonucleotides (AONs) – work by degrading the CUG expansion, or by binding to CUG expansion to inhibit RNA sequestration and sites for abnormal MBNL binding.
-
Recombinant Adeno-associated viral (rAAV) – stimulates overexpression of MBNL1, to prevent sequestration. Inhibition of CUG-BP1 activity via small molecules (pentamidine) or by inhibiting protein kinase C (involved in activating CUG-BP1) can also prevent sequestration.
-
Clustered regularly interspaced short palindromic repeats (CRISPR/Cas) – cleave and degrade CUG mRNA expansion.
The following recommendations are acquired from Consensus-based care recommendations for congenital and childhood-onset myotonic dystrophy type 1 published in 2019,[rx], and 2- Consensus Statement on Standard of Care for Congenital Muscular Dystrophies, published in 2014.[rx]
- Neurology – disclosure of diagnosis should address five items: diagnosis, prognosis, recurrence risk, treatment plan, and family/community support. Patients should be followed by an experienced multidisciplinary team in the neuromuscular clinic. Routine surveillance every 3 to 4 months for infants less than 12 months, and 4 to 6 months in toddlers of more than 12 months. Allied health teams include nurses, physical and occupational therapists, speech and language therapists, social workers, and genetic counselors. Focusing on the financial burden and psychosocial aspects is vital. Referral to ophthalmology and other services, as discussed below, is recommended.
- Respiratory – the primary goal is to monitor respiratory function, decrease secretions, and manage assisted ventilation. There is often an improvement in respiratory strength over time, and consideration for tracheostomy should be careful. Maintenance pulmonary therapy includes cough assist, breathe staking, etc. Pulmonary function testing includes vital capacity (<40% predict nocturnal hypoventilation), spirometry (>20% difference between sitting and supine vital capacity indicates diaphragmatic weakness and is a predictor of nocturnal hypoventilation). Other tests include peak cough flow, polysomnography, and blood gases. Pneumococcal and influenza vaccines are recommended, and palivizumab against RSV for children under two years of age.
- Cardiology – arrhythmias, myopathies, and structural cardiac diseases can present with lethargy, dyspnea, pallor, palpitations, and syncope. A twice-yearly assessment is required with closer follow-ups in symptomatic patients.
- Gastroenterology – serial monitoring of nutrition and growth, feeding, GI motility (GERD, dysmotility, constipation), and oral care is recommended. Feeding tubes with or without Nissen fundoplication, laxatives, antacids, proton pump inhibitors, antiemetics, and probiotics are advisable to consider.
- Malocclusion – teeth crowding, caries, and gingival hyperplasia (prolonged NPO) should prompt an orthodontist evaluation.
- Orthopedics and Rehabilitation – conservative or surgical interventions are required to manage joint contractures, scoliosis, foot, and spine deformities. Bracing, serial splinting, and assisting devices to include walkers, orthotics, scooters, and wheelchairs, might be required to facilitate standing/walking/sitting. Yearly evaluation is recommended, more frequent in younger children to assess motor development and function. Physical activity is essential as children will experience progressive improvements in proximal muscle strength.
- Pain Management – Patients with CMD are prone to developing contractures and can lead to painful spasms and joint pain. Adequate management of pain is important to achieve a good quality of life.[rx][rx][rx]
- Psychiatry – Patients with CMD with their disability are prone to develop depression and anxiety and must have a psychiatry/psychologist referral as part of multidisciplinary care.[rx]
Prevention
-
Yearly influenza vaccine
-
Pneumococcal vaccine (PPS 23)[rx]
-
Assess for, in the presence of corticosteroid intake, weight gain, dysphagia, constipation, malnutrition or prior main surgeries
-
Physical therapy to prevent muscle contractures. Promote daily or regular exercise, but if there is muscle pain, reduce activity intensity or frequency
-
Monitor for serum calcium, phosphorus, alkaline phosphatase, 25-hydroxyvitamin D (per semester), magnesium, PTH, urine calcium, and creatinine; Dual-energy x-ray absorptiometry at age three and annually; spine x-rays; bone age, especially if under corticosteroid therapy[rx]
-
Consider biphosphonates if there is a history of symptomatic vertebral fractures, not as prophylaxis
-
Baseline pulmonary function tests and biannually along with pediatric pulmonologist if the patient uses a wheelchair, age 12, or has a reduction of vital capacity of less than 80%
-
Family members or caregivers should be educated regarding manual ventilation bags, mechanical insufflation-insufflation devices.
Complications
The CTG expansions of DM affect multiple organ systems in addition to the musculoskeletal system and is associated with several complications.
Central Nervous System
-
Intellectual disabilities can be seen in all types but are not universal for all types of DM. Most commonly seen in the congenital form of DM.
-
Cerebrovascular accidents can occur secondary to DM-associated atrial fibrillation.
-
Anxiety and depression due to the loss of functional status
-
Hypersomnia and sleep apnea are common due to sleep cycle dysfunctions.
-
Ventriculomegaly is seen in congenital DM.
Ophthalmologic
-
Cataracts are almost universal in all patients with DM and are seen early with typical onset in the ’40s. Hyperopia and astigmatism can also occur.
Cardiac
-
Atrial arrhythmias, conduction system slowing, ventricular arrhythmias, cardiomyopathy, and early-onset heart failure.
Pulmonary
-
Pneumonia is common due to progressive loss of lung function and reduced lung volumes as a result of progressive neuromuscular-associated respiratory failure.
-
Increased risk of anesthesia-related pulmonary complications[rx]
Gastrointestinal
-
Facial diplegia and oropharyngeal dysphagia can result in dysphagia and an increased risk of aspiration.
-
There is also an increased incidence of gallstones and cholecystitis due to a hypertonic gallbladder sphincter.
-
Transaminitis and liver enzyme elevations are seen for unknown reasons.
-
Increased risk of post-anesthesia aspiration due to the weakness of pharyngeal musculature.[rx]
Endocrine
-
Insulin insensitivity can be seen
-
The loss of the seminiferous tubules results and testicular atrophy results in male infertility.
-
In women, there is an increased risk of abortion, miscarriage, pre-term birth rates, and dysmenorrhea.
Dermatologic
-
Androgenic alopecia with frontal balding and increased risk of basal cell carcinoma and pilomatrixoma.[rx]
Musculoskeletal
-
There is a progressive loss of motor function with increased wheelchair dependency towards the end of life.
-
Impairments in activities of daily living (ADLs) due to distal muscle weakness of the hands and ankle dorsiflexion.
-
Myalgias are very commonly noted.
Nutrition/gastrointestinal
-
Bulbar dysfunction is universal in individuals with SMA I; the bulbar dysfunction eventually becomes a serious problem for persons with SMA II and only very late in the course of disease for those with SMA III.
-
Gastrointestinal issues may include constipation, delayed gastric emptying, and potentially life-threatening gastroesophageal reflux with aspiration.
-
Growth failure can be addressed with gastrostomy tube placement as needed.
-
Nonambulatory individuals with SMA II and III are at risk of developing obesity [rx].
Respiratory
Children with SMA I and II (and more rarely, type III) who are treated with supportive care only have a progressive decline in pulmonary function due to a combination of weak respiratory muscles, reduced chest wall, and lung compliance, and a reduction in alveolar multiplication[rx].
-
Respiratory failure is the most common cause of death in SMA I and II.
-
Decreased respiratory function leads to impaired cough with inadequate clearance of lower airway secretions, hypoventilation during sleep, and recurrent pneumonia.
-
Noninvasive ventilation, such as BiPAP, and airway clearance techniques are commonly used to improve respiratory insufficiency in those with SMA.
Orthopedic
Scoliosis, hip dislocation, and joint contractures are common complications in individuals with SMA. Scoliosis is a major problem in most persons with SMA II and in half of those with SMA III. With supportive care only:
-
Approximately 50% of affected children (especially those who are nonambulatory) develop spinal curvatures of more than 50 degrees (which require surgery) before age ten years;
-
Later in the disease course, nonambulatory individuals can develop thoracic kyphosis [rx];
-
Progressive scoliosis impairs lung function and if severe can cause decreased cardiac output [rx].
Metabolic
An unexplained potential complication of SMA is severe metabolic acidosis with dicarboxylic aciduria and low serum carnitine concentrations during periods of intercurrent illness or prolonged fasting [rx].
Consultations
Neurology and Physical Medicine and Rehabilitation
-
Oversee the patient’s non-primary medical care and help direct and coordinate care and needs
-
Should evaluate the patient annually for swallowing difficulties and functional mobility and durable medical equipment (DME) needs
-
Assess if therapy is required to improve functional mobility
-
Medications to help treat myotonia and pain
-
Electrodiagnostic testing if indicated
Cardiology
-
Indicated for those with cardiac symptoms, an abnormal annual 12-lead ECG, or those without a previous cardiac evaluation who are older than 40 years of age.[rx]
-
Due to the high incidence of cardiac involvement, cardiology referral should be considered as part of the routine multidisciplinary treatment.
Pulmonology
-
Symptoms of respiratory insufficiency, recurrent pulmonary infections, or less than 50% of predicted FVC
Ophthalmology
-
Annual eye exam that includes a slit-lamp examination
High-Risk Obstetrics and Gynecology
-
Indicated for those pregnant or considering pregnancy due to miscarriage, preterm delivery, and respiratory difficulties during pregnancy
Genetic Counseling
-
Indicated for those with a diagnosis of myotonic dystrophy and considering procreation
Physical, Occupational Therapy, and Speech-Language Pathology (SLP)
-
Indicated for impaired function, DME evaluation, and myalgias and chronic pain
-
SLP is indicated for concerns for dysphagia or dysarthria
References
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