Muscular Dystrophy Disease

BASICS

DESCRIPTION

Inherited, progressive diseases of muscle with wide ranges of clinical expression. Included:

Congenital muscular dystrophy (CMD)
Congenital myotonic dystrophy
Duchenne's muscular dystrophy (DMD)
Becker's muscular dystrophy (BMD)
Myotonic dystrophy
Fascioscapulohumeral dystrophy (FSH)
Limb girdle dystrophy
Emery-Dreifuss muscular dystrophy (ED)
System(s) affected: Musculoskeletal, Nervous
Genetics: See Causes and Risk factors
Incidence/Prevalence in USA:
- Duchenne's muscular dystrophy (DMD): 1 per 3000 male births
- Myotonic dystrophy: 1 per 10,000 births
Predominant age:
- Birth to infancy: Congenital muscular dystrophy with or without cerebral involvement, congenital myotonic dystrophy
- Infancy to early childhood: Duchenne's muscular dystrophy (DMD), Becker's muscular dystrophy (BMD), fascioscapulohumeral dystrophy (FSH)
- Late childhood to adolescence: BMD, FSH, myotonic dystrophy
Predominant sex: Male > Female (DMD and BMD caused by defect in same gene)

SIGNS AND SYMPTOMS

DMD and BMD:
- Leg pain may be an early complaint
- Normal motor milestones until child begins to walk
- Clumsiness – frequent falls, toe-walking, waddling gait
- Weakness – inability to jump or climb stairs, weak neck flexors, Gower's sign, lumbar lordosis
- Pseudohypertrophy of calf muscles and contractures of heel cords
- Kyphosis and scoliosis
- Progressive decline in vital capacity
Myotonic dystrophy:
- Facial weakness – open, triangular mouth and droopy eyelids
- Sustained muscle contraction with percussion of thenar eminence
- Weakness in distal limbs
- High forehead with receding hairline
- Neonatal form – hypotonia, respiratory distress, hip dislocations
- Cataracts, gonadal dysfunction, cardiac conduction defects/arrhythmias
- Difficulty in letting go (myotonia) after handshake
FSH:
- Facial weakness – inability to completely close eyes or whistle, pouting expression with transverse smile
- Shoulder and proximal arm weakness: inability to do push-ups, horizontal clavicles, exaggerated biceps size ("Popeye" arms), winging of the scapula
- Retinal vascular abnormalities in most patients
ED:
- Toe walking and small biceps
- Contractures of neck, biceps, Achilles tendons – even without significant weakness
- Cardiac conduction abnormalities with risk of sudden death

CAUSES

X-linked: DMD and milder allelic form BMD have gene deletion, in 2/3 of patients, at Xp21.2 for production of "dystrophin"; ED have abnormal gene at Xq 28
Autosomal dominant: Myotonic dystrophy gene mapped to short arm of chromosome 19. FSH gene mapped to 4q35.

RISK FACTORS

X-linked: affected male on maternal side of family (although female carriers may rarely be symptomatic)
Autosomal dominant – affected parent: Myotonic dystrophy more severe if mother is affected parent
Autosomal recessive: CMD gene mapped to chromosome 6q2

DIAGNOSIS

LABORATORY

Creatine kinase:
- Marked elevation in DMD
- Moderate elevation in BMD, FSH
- Normal in congenital muscular dystrophy, late DMD

Drugs that may alter lab results:

Opiates including codeine, heroin, meperidine, and morphine
Dexamethasone
Ethanol
Digoxin
Furosemide
Aminocaproic acid
Halothane
Imipramine
Phenobarbital
Lithium
Clofibrate

Disorders that may alter lab results:

Polymyositis/dermatomyositis
Muscle trauma - exercise, seizures, IM injections, needle EMG
Hypothyroidism, hyperthyroidism
Myocardial infarction, stroke, sepsis, shock

PATHOLOGICAL FINDINGS

Muscle biopsy
- DMD: fiber splitting, necrosis, regeneration with interspersed fibrosis
- FSH: highest yield in supraspinatus muscle with occasional degenerating fibers and small angulated fibers with inflammatory cells
- ED: type I fiber atrophy

SPECIAL TESTS

EMG in myotonic dystrophy - high frequency repetitive, waxing and waning discharges ("dive-bomber" effect)

IMAGING

Brain MRI in CMD shows diffuse white matter changes resembling leukodystrophy

DIAGNOSTIC PROCEDURES

Muscle biopsy of moderately weak muscle (vastus lateralis, triceps) not studied by needle electromyography
Dystrophin level from muscle biopsy. In DMD dystrophin content is <3% normal; in BMD dystrophin content is <20% normal.
Prenatal diagnosis
- DMD and BMD: Dystrophin studies in chorionic villus sampling and amniocytes; analysis of fetal RBCs in maternal blood; Pre-implantation diagnosis
- CMD: Merosin-alpha-2 subunit in trophoblast

TREATMENT

APPROPRIATE HEALTH CARE

Outpatient with team approach - neurologist, orthopedic surgeon, physical and occupational therapists, social worker, and orthotist

GENERAL MEASURES

Physical therapy to maintain neuromuscular function
Orthoses to sustain walking and delay development of scoliosis
Respiratory care, ventilation during sleep for nocturnal hypoventilation syndrome

SURGICAL MEASURES

Surgical release of contractures or fixation of joints

ACTIVITY

Exercise as desired, but stop short of muscle pain or exhaustion

DIET

Monitor nutrition and fat stores because of increased caloric requirements

PATIENT EDUCATION

Family and individual counseling
Genetic counseling
Printed material and clinical services available through the Muscular Dystrophy Association, 3561 E. Sunrise Dr., Tucson, AZ 85718; (800) 221-1142

FOLLOW UP

PREVENTION/AVOIDANCE

Maternal carrier status evaluation in DMD (80% sensitive) and BMD (60% sensitive) by creatine kinase levels
DNA probes for carrier status determination and antenatal diagnosis in DMD and BMD
DNA linkage techniques in selected families for antenatal diagnosis of myotonic dystrophy

POSSIBLE COMPLICATIONS

Cardiac arrhythmias or myopathy
- Especially in ED
- In DMD (< 80%)
- In BMD (< 40%)
Hypertension – FSH
Dysphagia or acute gastric dilation – DMD, myotonic dystrophy
Malignant hyperthermia – DMD
Respiratory failure and early death – congenital muscular dystrophy (15%), neonatal-onset myotonic dystrophy (> 50%)
Endocrinopathies – myotonic dystrophy
Cataracts – myotonic dystrophy
Sensorineural hearing loss – FSH
Seizures and cerebral dysplasia – congenital muscular dystrophy with cerebral involvement (> 50%)
Increase in fetal breech presentation in female carriers of DMD

EXPECTED COURSE AND PROGNOSIS

DMD and BMD:
- Progressive weakness, contractures, inability to walk
- Kyphoscoliosis and respiratory compromise
- Early death (Duchenne's 16 ± 4 years; Becker's 42 ± 16 years)
Myotonic dystrophy (neonatal onset) and congenital muscular dystrophy with cerebral involvement:
- Progressive hypotonia and weakness
- Respiratory failure and early death
Other types:
- Slow progression and near normal life span

MISCELLANEOUS

ASSOCIATED CONDITIONS

Mental retardation - DMD (25%), myotonic dystrophy with early onset
Malignant hypothermia may be seen in patients with DMD

AGE-RELATED FACTORS

Pediatric: N/A
Geriatric: N/A
Others: N/A

PREGNANCY

Refer mother with myotonic dystrophy to perinatologist

OTHER NOTES

N/A

ABBREVIATIONS

CMD = Congenital muscular dystrophy
DMD = Duchenne's muscular dystrophy
BMD = Becker's muscular dystrophy
FSH = fascioscapulohumeral dystrophy

Clinical Investigations

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