Muscular Dystrophies Patarawan Woratanarat, MD, PhD Department of Orthopaedics Faculty of Medicine Ramathibodi Hospital

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Muscular DystrophiesPatarawan Woratanarat, MD,
PhDDepartment of OrthopaedicsFaculty of
Medicine Ramathibodi Hospital
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A 7-year-old boy presents with progressive
weakness of both legs for 4 years.
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Definition

• A group of noninflammation inherited distroders
• progressive degeneration and weakness of skeletal
  muscles
• without cause in peripheral / central nervous
  system

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Classification

• Sex-linked DMD, BMD, EDMD
• Autosomal recessive LGMD, infantile FSHD
• Autosomal dominant FSHD, distalMD, ocular MD,
  oculopharyngeal MD.

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Duchenne Muscular dystrophy

• Guillaume Benjamin Amand Duchenne
• (French neurologist, 1860s)

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Duchenne Muscular dystrophy

• Etiology
• single gene defect
• Xp21.2 region
• absent dystrophin

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Duchenne Muscular dystrophy
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Duchenne Muscular dystrophy
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DMD pathology
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DMD Epidemiology

• Most common
• male, Turner syndrome
• 13500 live male birth
• 1/3 new mutation
• 65 family history

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DMD Clinical manifestation

• Onset age 3-6 years
• Progressive weakness
• Pseudohypertrophy of calf muscles
• Spinal deformity
• Cardiopulmonary involvement
• Mild - moderate MR

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Pseudohypertrhophy of calf muscle, Tip toe
gait forward tilt of pelvis, compensatory lordosis
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Disappearance of lordosis while sitting
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DMD Diagnosis
Gowers sign
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DMD Diagnosis

• Increase CPK (200x)
• Myopathic change in EMGBx m. degeneration
• Immunoblotting Absence dystrophin
• DNA mutation analysis

• Gait
• absent DTR
• Ober test
• Thomas test
• Meyeron sign
• Macroglossia
• Myocardial deterioration
• IQ 80

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Western blot Normal dystrophin bands (230kD)
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DMD Natural history

• Progress slowly and continuously
• muscle weakness
• lower --gt upper extremities
• unable to ambulate 10 year (7-12)
• death from pulmonary/ cardiac failure 2-3rd
  decade

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DMD Treatment

• Prednisolone
• Dystrophin replacement
• Maintain function
• PMR
• orthosis
• cardiopulmonary Rx
• Counselling

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DMD Treatment

• Surgery
• Foot ankle Achillis, Tibialis posterior
  release
• Knee Yount, hamstring release
• Hip Ober, modified Soutter procedure

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DMD Treatment
Percut. Tenotomy Achillis tendon
An 8-yr-old boy Unable to stand
Ambulate with orthosis
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DMD Treatment

• Surgery
• Upper extremity -
• Spinal deformity posterior spinal fusion
  pelvis

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Becker muscular dystrophy

• Peter Emil Becker
• (German doctor, 1950s)

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Becker muscular dystrophy

• Milder version of DMD
• Etiology
• single gene defect
• short arm X chromosome
• altered size decreased amount of dystrophin

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Becker muscular dystrophy
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BMD Epidemiology

• Less common
• 1 30000 live male birth
• Less severe
• Family history atypical MD

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BMD Clinical manifestation

• Similar less severe than DMD
• Onset age gt 7 years
• Pseudohypertrophy of calf
• Equinous and varus foot
• High rate of scoliosis
• Less frequent cardiac involvement

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BMD Diagnosis

• The same as DMD
• Increase CPK (lt200x)
• Decrease dystrophin and/or altered size

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BMD

• Natural history
• Slower progression
• ambulate until adolescence
• longer life expectancy

• Treatment
• the same as in DMD
• forefoot equinous plantar release, midfoot
  dorsal-wedge osteotomy

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Emery-Dreifuss muscular dystrophy

• Etiology
• X-linked recessive
• Xq28
• Emerin protein (in neuclear membrane)

• Epidemiology
• Male typical phenotype
• Female carrier partial

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EDMD Clinical manifestation

• Muscle weakness
• Contracture
• Neck extension, elbow, achillis tendon

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EDMD Clinical manifestation

• Scoliosis common, low incidence of progression
• Bradycardia, 1st degree AV block ? sudden death

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EDMD

• Natural history
• 1st 10 y mild weakness
• Later contracture, cardiac abnormality
• 5th-6th decade can ambulate
• Poor prognosis in obesity, untreated equinus
  contractures.

• Diagnosis
• Gowers sign
• Mildly/moderately elevated CPK
• EMG myopathic
• Normal dystrophin

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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 gt 40 degrees
• Cardiologic intervention
• Cardiac pacemaker

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Limb-girdle muscular dystrophy

• Eitology
• Autosomal recessive at chromosome 15q
• Autosomal dominant at 5q
• Epidemiology
• Common
• More benign

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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
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Limb-girdle muscular dystrophy

• Clinical manifestation
• Age of onset 3rd decade
• Initial pelvic/shoulder m. (proximal to distal)
• Similar distribution as DMD

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LGMD

• Diagnosis
• Same clinical as DMD/BMD carriers
• Moderately elevated CPK
• Normal dystrophin

• Classification
• Pelvic girdle type
• common
• Scapulohumeral type
• rare

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LGMD

• Treatment
• Similar to DMD
• Scoliosis mild, no Rx.

• Natural history
• Slow progression
• After onset gt 20 y contracture disability
• Rarely significant scoliosis

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Fascioscapulohumeral muscular dystrophy

• Etilogy
• Autosomal dominant
• Gene defect (FRG1)
• Chromosome 4q35
• Epidemiology
• Female gt male

• Clinical manifestation
• Age of onset late childhood/ early adult
• No cardiac, CNS involvement

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FSMD Clinical manifestation

• Muscle weakness
• face, shoulder, upper arm
• Sparing
• Deltoid
• Distal pectoralis major
• Erector spinae

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• Popeye appearance
• Lack of facial mobility
• Incomplete eye closure
• Pouting lips
• Transverse smile
• Absence of eye and forehead wrinkles

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FSMD Clinical manifestation

• Winging scapula
• Markedly decreased shoulder flexion abduction
• Horizontal clavicles
• forward sloping
• Rare scoliosis

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FSMD

• Treatment
• Posterior scpulocostal fusion/ stabilization
  (scapuloplexy)

• Diagnosis
• PE, muscle biopsy
• Normal serum CPK
• Natural history
• Slow progression
• Face, shoulder m. ? pelvic girdle, tibialis ant
• Good life expectancy

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Distal muscular dystrophy

• Autosomal dominant trait
• Rare
• Dysferlin (mb prot) defect
• Age of onset after 45 y

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Distal muscular dystrophy

• Initial involvement intrinsic hands, claves,
  tibialis posterior
• Spread proximally
• Normal sensation

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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

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Congenital muscular dystrophy

• Etiology
• Autosomal recessive
• Integrin, fugutin defect

Laminin ?2 chain merosin
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CMD

• Epidemiology
• Rare
• Both male and female
• Classification
• Merosin-negative
• Merosin-positive
• Neuronal migration
• Fukuyama
• Muscle eye-brain
• Wlaker-Warburg

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CMD Clinical manifestation

• Stiffness of joint
• Congenital hip dislocation, subluxation
• Achillis tendon contracture, talipes equinovarus
• Scoliosis

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CMD

• Diagnosis
• Muscle Bx Perimysial and endomysial fibrosis

• Treatment
• Physical therapy
• Orthosis
• Soft tissue release
• Osteotomy

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Summary
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Summary
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Thank you
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Infantile fascioscapulohumeral muscular dystrophy

• 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

• Etiology
• Autosomal recessive
• Unidentified gene

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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

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Ocular muscular dystrophy

• Rare
• Age of onset adolescence
• Extraocular muscle weakness ? diplopia ? limit
  ocular movement
• May involve proximal upper extremities
• Slowly progressive

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Oculopharyngeal muscular dystrophy

• Autosomal dominant with complete penetrane
• Age of onset 3rd decade
• Ptosis in middle life

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OPMD

• Pharyngeal involvement
• Dysarthria
• Dysphasia
• Repetitive regurgitation
• Frequently choking