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Muscular Dystrophies Patarawan Woratanarat, MD, PhD Department of Orthopaedics Faculty of Medicine...
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Transcript of Muscular Dystrophies Patarawan Woratanarat, MD, PhD Department of Orthopaedics Faculty of Medicine...
Muscular Dystrophies
Patarawan Woratanarat, MD, PhD Department of Orthopaedics
Faculty of Medicine Ramathibodi Hospital
A 7-year-old boy presents with progressive weakness of both legs for 4 years.
Definition A group of noninflam
mation inherited distroders
progressive degener ation and weakness o
f skeletal muscles without cause in peri
pheral / central nervo us system
Classification
- Sex linked: DMD, BMD, EDMD Autosomal recessive: LGMD, infantile
FSHD Autosomal dominant: FSHD, distalMD,
ocular MD, oculopharyngeal MD.
Duchenne Muscular dystrophy
Guillaume Benjamin Amand Duchenne (French neurologist, 1 8 6 0 s)
Duchenne Muscular dystrophy
Etiology single gene def
ect Xp21.2 region absent dystrop
hin
Duchenne Muscular dystrophy
Duchenne Muscular dystrophy
DMD: pathology
DMD: Epidemiology Most common male, Turner syn
drome 1:3500 live male
birth 13/ new mutati
on 6 5 % family histo
ry
DMD: Clinical manifestation
- Onset : age 3 6 years Progressive weaknes
s Pseudohypertrophy o
f calf muscles Spinal deformity Cardiopulmonary inv
olvement - Mild moderate MR
Pseudohypertrhophy of calf muscle, Tip toe gaitforward tilt of pelvis, compensatory lordosis
Disappearance of lordosis while sitting
DMD: Diagnosis
Gower’s sign
DMD: Diagnosis
Gait absent DTR Ober test Thomas test Meyeron sign Macroglossia Myocardial dete
nnnnnnnnn 80IQ ~
20Increase CPK (0
Myopathic change inEMGnnn nn nnnnnnnnnnnn
Immunoblotting: Abs ence dystrophin
DNA mutation analysis
Western blotNormal dystrophin bands (230kD)
DMD: Natural history Progress slowly and c
ontinuously muscle weakness
-- lower > upper extremities
unable to ambulate: -10 year (7 12)
death from pulmonar -y/ cardiac failure: 2 3 rd decade
DMD: Treatment Prednisolone Dystrophin replace
ment Maintain function
PMR orthosis cardiopulmonary R
n Counselling
DMD: Treatment
Surgery Foot & ankle: Achillis, Tibialis posterior
release Knee: Yount, hamstring release Hip: Ober, modified Soutter procedure
An 8-yr-old boyUnable to stand
Percut. TenotomyAchillis tendon
Ambulate with orthosis
DMD: Treatment
DMD: Treatment Surgery
nnnnnnnnnn -: Spinal deformity: posterior spinal fusion +
pelvis
Becker muscular dystrophy
Peter Emil Becker (German doctor, 1950s)
Becker muscular dystrophy
Milder version of DMD
Etiology single gene defect short arm X chrom
osome altered size & decr
eased amount of dystrophin
Becker muscular dystrophy
BMD: Epidemiology
Less common 1: 30000 live male birth
Less severe Family history: atypical MD
BMD: Clinical manifestation
Similar & less severe than DMD Onset: age > 7 years Pseudohypertrophy of calf Equinous and varus foot High rate of scoliosis Less frequent cardiac involvement
BMD: Diagnosis The same as DMD Increase CPK (<20
0x) Decrease dystrop
hin and/or alteredsize
BMD
Nat ur al hi st or y Slower progression ambulate until adoles
cence longer life expectancy
Treatment the same as in DM
D forefoot equinous:
plantar release, mi -dfoot dorsal wedg
e osteotomy
- Emery Dreifuss muscular dystrophy
Epidemiology Male: typical phenoty
pe Female carrier: partial
Etiology - X linked recessive 28Xq Emerin protein (in
neuclear membrane)
EDMD: Clinical manifestation Muscle weakness Contracture
Neck extension, elbow, achillis tendon
EDMD: Clinical manifestation
Scoliosis: common, low incidence of progression
Bradycardia, 1st degree AV block sudden death
EDMD
Diagnosis Gower’s sign Mildly/moderately
elevated CPK EMG: myopathic Normal dystrophin
Natural history 1st 10 y: mild weakness Later: contracture,
cardiac abnormality 5th-6th decade: can
ambulate Poor prognosis in
obesity, untreated equinus contractures.
EDMD: Treatment Physical therapy
Prevent contracture: neck, elbow, paravertebral muscles
For slow progress elbow flexion contracture Soft tissue contracture
Achillis lengthening, posterior ankle capsulotomy + anterior transfer of tibialis posterior
Spinal stabilization For curve > 40 degrees
Cardiologic intervention Cardiac pacemaker
- Limb girdle muscular dystrophy
Eitology Autosomal recessive at chromosome
15q Autosomal dominant at 5q
Epidemiology Common More benign
- Limb girdle muscular dystrophy
an absence of functional sarcoglycans components of the dystrophin glycoprotein complex (DCG).
Other LGMD result from the absence of functional caveolin-3
- Limb girdle muscular dystrophy
Clinical manifestation Age of onset: 3rd
decade Initial:
pelvic/shoulder m. (proximal to distal)
Similar distribution as DMD
LGMD Classification
Pelvic girdle type common
Scapulohumeral type
rare
Diagnosis Same clinical as
DMD/BMD carriers Moderately
elevated CPK Normal dystrophin
LGMD Natural history
Slow progression After onset > 20
y: contracture & disability
Rarely significant scoliosis
Treatment Similar to DMD Scoliosis: mild, no
Rx.
Fascioscapulohumeral muscular dystrophy
Etilogy Autosomal
dominant Gene defect
(FRG1) Chromosome
4q35 Epidemiology
Female > male
Clinical manifestation Age of onset: late
childhood/ early adult
No cardiac, CNS involvement
FSMD: Clinical manifestation
Muscle weakness face, shoulder,
upper arm
Sparing Deltoid Distal pectoralis
major Erector spinae
“Popeye” appearance Lack of facial
mobility Incomplete eye
closure Pouting lips Transverse smile Absence of eye and
forehead wrinkles
FSMD: Clinical manifestation
Winging scapula Markedly decreased
shoulder flexion & abduction
Horizontal clavicles forward
sloping
Rare scoliosis
FSMD Diagnosis
PE, muscle biopsy Normal serum CPK
Natural history Slow progression Face, shoulder m.
pelvic girdle, tibialis ant
Good life expectancy
Treatment Posterior scpulocostal
fusion/ stabilization (scapuloplexy)
Distal muscular dystrophy
Autosomal dominant trait
Rare Dysferlin (mb prot)
defect Age of onset: after
45 y
Distal muscular dystrophy
Initial involvement: intrinsic hands, claves, tibialis posterior
Spread proximally Normal sensation
DD: Classification Welander distal myopathy Finnish/Markesbery distal myopathy Miyoshi distal myopathy Nonaka distal myopathy Gower: autosomal dominant, Chromosome 14 Hereditary inclusion-body myositis Hereditary inclusion-body myuositis Distal myopathy with vocal cord & pharyngeal
weakness
Congenital muscular dystrophy
Etiology Autosomal recessive Integrin, fugutin defect
Laminin 2 chainmerosin
CMD: Epidemiology
Rare Both male and female
Classification Merosin-negative Merosin-positive Neuronal migration
Fukuyama Muscle eye-brain Wlaker-Warburg
CMD: Clinical manifestation
Stiffness of joint Congenital hip
dislocation, subluxation
Achillis tendon contracture, talipes equinovarus
Scoliosis
CMD Diagnosis
Muscle Bx: Perimysial and endomysial fibrosis
Treatment Physical therapy Orthosis Soft tissue
release Osteotomy
SummaryClinical DMD LGMD FSMD DD CMD
Incidence common less Not common
Rare Rare
Age of onset
3-6 y 2nd decade
2nd decade
20-77 y At/ after birth
Sex Male Either sex M = F Either sex Both
Inheritance
Sex-linked recessive
AR, rare AD
AD AD Unknown
Muscle involve.
Proximal to distal
Proximal to distal
Face & shoulder to pelvic
Distal Generalized
Muscle spread until late
Leg, hand, arm, face, larynx,eye
Upper ex, calf
Back ext, hip abd, quad
Proximal -
SummaryClinical DMD LGMD FSMD DD CMDPseudohypertrophy
80% calf
< 33% Rare no No
Contracture Common Late Mild, late Mild, late Severe
ScoliosisKyphoscoliosis
Common, late
Late - - ?
Heart Hypertrophytachycardia
Very rare
Very rare Very rare Not observed
Intellectual decrease Normal Normal Normal ?
Course Stead, rapid
Slow Insidious benign Steady
Thank you
Infantile fascioscapulohumeral muscular dystrophy
Etiology Autosomal
recessive Unidentified gene
Clinical manifestation Facial diplegia Sensorinueral hearing
loss Mobius type of facial
weakness Walk with hands and
forearms folded across upper buttocks
**Marked & progressive lumbar lordosis (pathog)
Less common equinous, scoliosis
IFSMD Natural history
Infancy: facial diplegia
Childhood: sensorineural hearing loss
2nd decade of life: wheelchair bound, severely compromised pulmonary function
Treatment Flexible
equinous/equinovarus foot: AFO + TAL
Hip flextion contracture: no Rx in ambulate pt.
Spinal deformity in wheelchai ambulator: orthosis+ post spinal fusion with instrumentation
Scapulothoracic stabilization: not necessary
Ocular muscular dystrophy
Rare Age of onset: adolescence Extraocular muscle weakness
diplopia limit ocular movement May involve proximal upper
extremities Slowly progressive
Oculopharyngeal muscular dystrophy
Autosomal dominant with complete penetrane
Age of onset: 3rd decade
Ptosis in middle life
OPMD Pharyngeal
involvement Dysarthria Dysphasia Repetitive
regurgitation Frequently
choking