PROGRESSIVE MUSCULAR DYSTROPHIES

BSPT 3Y2-1 HGD101

2. SEMESTER, 17-18

AMIHAN – INTRO, ANATOMY AND PHYSIOLOGY, PT MX

CABACUNGAN – PHARMACOLOGICAL MX
FLORES – MEDICAL MX
GONZALES – LIMB GIRDLE MUSCULAR DYSTROPHY
MAJAM - BECKER MUSCULAR DYSTROPHY, DIAGNOSIS
MEDENILLA - PATHOGENESIS
NANIT - ETIOLOGY
PATRON - EMERY-DREIFUSS MUSCULAR DYSTROPHY
RAVANERA - FASCIOSCAPULOHUMERAL MUSCULAR DYSTROPHY
SALVATERA - DUCHENNE MUSCULAR DYSTROPHY
VALDE - PROGNOSIS
GAOIRAN - EPIDEMIOLOGY

 PROGRESSIVE MUSCULAR DYSTROPHIES (PMD)

◦ Abnormality of any component of the lower motor neuron (anterior horn cell, peripheral nerve,
neuromuscular junction, presynaptic or postsynaptic region), or muscle
◦ Is the largest and most common group of progressive and neuromuscular disorders of the childhood.
◦ genetic in origin
◦ Characterized by ongoing symmetrical muscle wasting without neural of sensory deficits but with
increasing deformity and disability.
 4 TYPES OF MUSCULAR DYSTROPHY
◦ Duchenne's MD (X-linked; recessive)
◦ Becker's MD (X-linked; recessive)
◦ Fascioscapulohumeral MD (autosomal dominant or recessive; 4q35)
◦ Limb-girdle Dystrophy (autosomal dominant; 15q15.1)
 PMD
◦ In all forms of MD there is a primary degeneration of muscles with a gradual loss of strength, but each
type differs as to which muscle group are affected.
 RELATED ANATOMY AND PHYSIOLOGY
 TYPES OF MUSCLE TISSUE
◦ Skeletal
◦ Cardiac
◦ Smooth

 MUSCLE PROTEINS
◦ Active: Contractile
▪ Myosin heavy chain – motor for ms cxn; binds to action to generate contraction force.
▪ Actin – binds with myosin to translate force and shorten sarcomere
◦ Active: Regulatory
▪ Tropomyosin – Regulates the interaction bet actin and myosin, stabilizes actin filament
▪ Troponin – influences the poistion of tropomyosin; binds with calcium ions
▪ Myosin light chain – influences the contraction velocity of the sarcomere; modulates the kinetics
of cross bridge cycle
◦ Structural
▪ Nebulin – anchors actin to z disc
▪ Titin – creates passive tension within the stretched sarcomere; acts as a molecular spring
▪ Desmin – helps to stabilize the longitudinal and lateral alignment of adjacent sarcomeres
▪ Vimentin – helps maintain periodicity of z discs
▪ Skelemin – helps stabilize the position of M lines
▪ Dystrophin – provides structural stability to the cytoskeleton and sarcolemma of the muscle fiber
 ▪ Integrins – stabilizes the cytoskeleton of the muscle fiber
 FUNCTIONS OF MUSCULAR SYSTEM
◦ Body movement (Locomotion)
◦ Maintenance of posture
◦ Respiration
◦ Diaphragm and intercostal contractions
◦ Communication (Verbal and Facial)
◦ Constriction of organs and vessels
◦ Peristalsis of intestinal tract
◦ Vasoconstriction of blood vessels and other structures (pupils)
◦ Heart beat
◦ Production of body heat (Thermogenesis)
 EPIDEMIOLOGY
◦ 20-30 per 100,000 live births
◦ DMD occurs 1 in 3500 live male births
◦ BMD occurs 1 to 3 in 100,000 live male births
◦ Male > Female
◦ BMD: 12-27 per million
◦ FSHD: 10-20 per million live births
 ETIOLOGY
◦ All dystrophies are inherited disorders
◦ DMD & BMD are X-linked recessive caused by mutations in the dystrophin gene (muscle protein) in
the Xp21 gene loci
◦ FSH is AD disorder with the onset in early adolescence
◦ The son/daughter of a person affected with FSH is at 50% risk of inheriting the defective gene
◦ LGD maybe inherited in several ways but is usually and AR d/o of late chilhood or adolescence.
◦ Parents of LGD patients will not exhibit the disorder but there is a 1 in 4 chance of every pregnancy
producing a child (son/daughter)
◦ FSH & LGD may affect both gender
 PATHOGENESIS
◦ AUTOSOMAL DOMINANT
▪ 50-50 chance
▪ X-linked dominant
▪ M/F
▪ Damaged gene: Dominant gene
◦ AUTOSOMAL RECESSIVE
▪ 50% unaffected
▪ 25% carrier
▪ X-linked recessive
◦ Dystrophin is localized to the intracellular side of the plasma membrane of all myogenic cells, certain
types of neurons, and in small amounts of other cell types
◦ Dystrophin deficiency at the plasma membrane of muscle fibers disrupts the membrane cytoskeleton
and leads to the secondary loss of other components of the muscle cytoskeleton
◦ There will be a replacement of the muscle and eventual failure of regeneration with muscle fiber death
and fiber loss
 DUCHENNE MUSCULAR DYSTROPHY (DMD)
◦ ETIOLOGY
▪ X-linked disorder
▪ Xp21 gene loci
▪ DMD/BMD gene occupies 2.5 million base pairs of DNA on the X chromosome and is about 10x
larger than the next largest gene identified to date
▪ Most common and most severe of the muscular dystrophies
▪ ABSENT or LOSS of dystrophin gene
▪ Onset : age 3-6 years
◦ CLINICAL MANIFESTATIONS
▪ (+) Gower sign
▪ (+) Waddling gait
▪ (+) Posterior Axillary Depression Signwide arch to the mandible and maxilla with separation of
teeth
▪ Frequent falls, difficulty climbing stairs
▪ (+) Tip toes contracture of TAs and Peroneals
▪ Increased lumbar lordosis
▪ Pseudohypertrophy
▪ Enlarged tongue (macroglossia)
▪ Proximal muscle weakness
▪ Weakness of neck flexors
▪ 10-12 y/o are no longer able to walk
▪ Currently no cure and death occurs in mid twenties due to respiratory insufficiency and/or heart
failure

GOWER'S SIGN
 Trendelenburg Gait
◦ Trendelenburg or “Gluteus Medius” gait pattern in a male with DMD. Note the lateral lean over the
stance side due to hip abductor weakness; ankle dorsiflexion weakness necessitates swing phase in
circumduction for clearance.
 Myopathic Stance
◦ “Myopathic” stance in an eight-year-old male with DMD. Notice the lumbar lordosis to compensate for
hip extensor weakness and primarily forefoot contact to compensate for knee extensor weakness.

◦ SECONDARY COMPLICATIONS
▪ Contractures
▪ Scoliosis
▪ Depressed tendon reflexes
▪ Respiratory Involvement
▪ Cardiomyopathy
▪ ↓ IQ
▪ Anthropometric changes
◦ DMD DIAGNOSIS
▪ Gait
▪ Absent/ or ↓DTR
▪ Ober test
▪ Thomas test
▪ Myocardial deterioration
▪ Increase CPK (200x)
▪ Myopathic change in EMGBx: m. degeneration
▪ Immunoblotting: Absence dystrophin
▪ DNA mutation analysis
 BECKER MUSCULAR DYSTROPHY (BMD)
◦ resembles DMD but with later onset and slow rate of progression
◦ ambulatory beyond 16 years of age
◦ some may be wheelchair users in their late 20s
◦ proximal muscle weakness
◦ muscle cramps are a common complain
 ◦ scoliosis and contractures are common when the child becomes wheelchair dependent
◦ Later life expectancy
◦ Milder version of DMD
◦ Later onset and a much slower rate of progression
▪ ETIOLOGY:
 single gene defect
 short arm X chromosome
 altered size & decreased amount of dystrophin
▪ CLINICAL MANIFESTATIONS
 Similar & less severe than DMD
 Onset: age > 7 years
 Pseudohypertrophy of calf
 EquinUs and varus foot
 High rate of scoliosis
 Less frequent cardiac involvement
 EMERY-DREIFUSS MUSCULAR DYSTROPHY
▪ ETIOLOGY
 X-linked recessive
 Xq28
 Emerin protein (in neuclear membrane)
▪ EPIDEMIOLOGY
 Male: typical phenotype
 Female carrier: partial
▪ COMPLICATIONS
 Muscle weakness
 Contracture
 Neck extension, elbow, achilles tendon
 Scoliosis: common, low incidence of progression
 Bradycardia, 1st degree AV block - sudden death
 FASCIOSCAPULOHUMERAL MUSCULAR DYSTROPHY (FSHMD)
◦ mild form of MD
◦ weakness and atrophy of the facial and shoulder girdle muscles
◦ Earliest sign: inability to close eyes
◦ expressionless face even when laughing and crying
◦ forward shoulders and winging may develop
◦ facial flattening, pouting lips, inability to whistle (Infants: inability to suckle)
◦ LE weakness may be delayed
▪ CLINICAL MANIFESTATIONS
 contractures, deformity, & hypertrophy are UNCOMMON
 Winging scapula
 Markedly decreased shoulder flexion & abduction
 Horizontal clavicles
 forward sloping
 ▪ Muscles affected
 Zygomaticus
 Orbicularis oris
 Orbicularis oculi
 Levator scapulae
 Serratus Anterior
 Rhomboids
 Upper Trapezius
 LIMB GIRDLE MUSCULAR DYSTROPHY
◦ slow progression
◦ mild impairment
◦ weakness at onset most often affects the pelvic or shoulder girdle musculature or both
◦ Slow course
◦ Mild impairment
◦ Muscle weakness of the upper (deltoid and biceps) arm and pelvic muscles
◦ Usually noticed in late adolescence or early adulthood but as ate as the person’s 40
◦ More difficult to diagnose d/t lack of consistent clinical features
◦ Scapular winging, lumbar lordosis, abdominal protrusion, waddling gait, poor balance, & inability to
raise arms may also develop
▪ ETIOLOGY
 Autosomal recessive at chromosome 15q
 Autosomal dominant at 5q
▪ EPIDEMIOLOGY
 Common
 More benign
▪ CLINICAL MANIFESTATIONS
 Age of onset: 3rd decade
 Initial: pelvic/shoulder m. (proximal to distal)
 Similar distribution as DMD
 normal dystrophin
 Natural history
 Slow progression
 After onset > 20 y: contracture & disability
▪ DIAGNOSIS
 Family history
 Physical Examination
◦ Diagnostic testing
▪ EMG
 Demonstrates short (weak duration)
 Weak bursts ( decreased amplitude) of electrical activity on affected muscles
 Muscle Biopsy
 Shows variation in size of muscle fibers
 Later stages: fat and connective tissue deposits
 Absence of dystrophin
 Demonstrates short (weak duration)
  Weak bursts ( decreased amplitude) of electrical activity on affected muscles
▪ Serum enzymes
 Creatinine kinase levels 2 to 10 times normal
 Levels are high in the first 2 years of life before the onset of clinical weakness
 But do not return to normal levels of CK until severe muscle wasting and
disability occur
▪ Muscle biopsy
 Shows variation in size of muscle fibers
 Later stages: fat and connective tissue deposits
 Absence of dystrophin
 Demonstrates short (weak duration)
 Weak bursts ( decreased amplitude) of electrical activity on affected muscles
▪ Chorion biopsy
 Prenatal biopsy diagnostic technique in which DNA is removed as early as 10
weeks gestation
 The laboratory testing can detect a deletion of the dystrophin gene in
approximately 70% of fetuses with DMD

 MEDICAL MANAGEMENT
◦ There is no known treatment to halt the progression
◦ Treatment is directed toward maintaining function of the unaffected muscle groups for as long as
possible
◦ Prevent secondary complications
◦ PHYSICAL THERAPY
◦ Cell and gene therapy
 PHARMACOLOGICAL MANAGEMENT
◦ Glucocorticoid therapy to slow the progression
◦ Increases myogenisis and enhances the expression of dystrophin thereby improving muscle force and
function and diminishing deterioration
◦ Prednisolone & Deflazcort
 PHYSICAL THERAPY MANAGEMENT
◦ Breathing techniques
◦ Home modifications
◦ Standing equipments
◦ Wheelchair
◦ Splints
◦ Active ROM exercises
◦ Grab bars
◦ Overheadslings
◦ Prolonged positioning
◦ Pool therapy
◦ Ambulation exercises
◦ Lift equipment etc
 PROGNOSIS
◦ All forms of MD are Progressive, but prognosis varies
◦ The earlier clinical signs appear, the more rapid, progressive and disabling the dystophy
 ◦ DMD: rapid and usually results to death by age 20 due to respiratory muscle dysfunction or cardiac
weakness
◦ BMD: usually live into their 40s and death secondary to respiratory dysfunction or heart failure
◦ FSH & LGD: have a normal life span
 REFERENCES
◦ Pediatric rehabilitation : principles and practice (Molnar) 4th edition
◦ Braddom's Physical Medicine & Rehabilitation 4th edition
◦ Pictures from the internet