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