22213745 Muscular Dystrophy

8/14/2019 22213745 Muscular Dystrophy

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Muscular Dystrophies

Lhedaven C. Santos R.N.


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Muscular Dystrophies

Progressive hereditary degenerative diseases of the skeletal muscle

Intact spinal motor neurons, muscular nerves, and nerve endings in

the presence of severe degenerative changes in muscle fibers

General features:

symmetrical distribution of weakness and atrophy

intact sensation

preservation of reflexes

heredofamilial

Classified by clinical types, pattern of inheritance and by the

abnormal gene or its protein product


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Etiology The abnormal gene and the gene product for Duchenne and

Becker identified by Kunkel in 1986

Dystrophin is the protein encoded by the affected gene

Dystrophin absent in Duchenne and structurally abnormal in

Becker

Dystrophin in normal skeletal and cardiac muscle is localized in

the sarcolemma (cytoplasmic site) and interacts with F-actin of

the cytoskeleton (reinforcing structure of muscle cell)

Dystrophin also bound to a complex of sarcolemmal proteinsknown as dystrophin associated proteins (DAP)


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Etiology

Loss of dystrophin leads to disruption of the

dystroglycan-protein complex rendering the

sarcolemma susceptible to breaks duringcontraction

These defects are shown to allow ingress of

EC fluid and calcium which activateproteases and cause protein degradation

Leakage of CK into serum is then seen


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Duchenne MD

Incidence rate 13-33 per 100,000 male births annually

X-linked recessive

30% of cases represent new mutations

Females can present disease if only one chromosome is present

(Turner) or due to inactivation of the normal paternal X

chromosome in large proportion of embryonic cells (decreased

expression of the normal dystrophin allele)


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Clinical findings

Recognized usually in third year of life due to delay

in motor milestones or due to frequent falls

Latter sway back and waddling gait (weak gluteus

medius) as well as climbing stairs become more

affected

Elevated CK may be the first clue


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Clinical findings

Muscles mostly affected

early: illiopsoas, quadriceps, gluteal

latter: pretibial, pectoral girdle (serratus, pectorals,latissimus) and upper limbs (biceps, brachioradialis)

Muscles pseudo-hypertrophied

gastronemius, lateral vastus and deltoid

have rubbery feel and are less strong and hypotonic

than normals


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Clinical findings

Weakness of abdominal and paravertebral muscles

- lordotic posture and protuberant abdomen when

standing and rounded back when sitting Weak extensors of the knee and hip - difficult to

climb stairs or from a chair

Use of hands to compensate for weakness when

rising from sitting position or from floor


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Gowers maneuver

4 point position

Hands up to thigh

alternately


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Clinical Findings

Ocular, facial and bulbar and hand muscles are usually

spared

Limbs later become flaccid but as disability progresses

fibrous contractures appear due to immobility

Early in the disease there is equinovarus due to weak

pretibial and peroneal muscles; later knee contractures

appear due to weak quadriceps

Pelvic tilt also seen later due to contracture of hip flexors

this is compensated with lordosis when standing


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Clinical Findings

Contractures contribute to eventual loss of ambulation

Scoliosis appears due to unequal weakening of paravertebral

muscles usually after walking is not possible

As muscle atrophy progresses DTRs are lost

Bones are thin and demineralized

Can have mild mental retardation

Although smooth muscle is usually spared heart is usuallyaffected


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Clinical Findings

Cardiac problems:

Arrhythmias

prominent R waves in right precordial leads and deep Q waves in

left precordial and limb leads as result of replacement fibrosis of the

basal part of the left ventricular wall

Death is usually 2dary to pulmonary infection and respiratory

failure or in some due to cardiac decompensation

No more than 25% of patients survive beyond 25 years


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Muscle biopsy

In all dystrophies loss of

muscle fibers, residual fibers of

small and larger size in

haphazard arrangement andincrease in lipocytes and

fibrosis

Duchenne -Early: segmental degeneration,

phagocytosis and evidence of regenerative

activity

basophilia of sarcoplasm

hyperplasia and nucleolation of sarcolemmal

nuclei

myotubes and myocytes

Necrotic sarcoplasm and sarcolemma

removed by mononuclear cells

Hyalinization of the sarcoplasm of muscle

fibers as marker of irritability of m fiber

Fibers eventually degenerate and disappeardue to exhaustion of regenerative capacity


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Becker Muscular Dystrophy

Incidence estimated to be 3-6 per 100,000 male births

X-linked disorder

Later onset than Duchenne (mean age 12 years but range 5-45 y/o)

Affects same muscles as Duchennes MD Patient non-ambulatory at 25-30 y/o

Death in 5th decade in most

Less frequent cardiac involvement

Serum CK 25-200 times normal

EMG: fibrillations, positive waves, low amplitude polyphasic MUP


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Facioscapulohumeral MD Slowly progressive or nearly complete arrest

Usually autosomal dominant 4 q35

Subvariety w/o facial weakness

Onset usually 6-20 y/o Difficulty raising arms above head and winging of the

scapulae first manifestations

Invariably weakness of lower trapezius and sternal part of

pectoralis

Deltoids unusually large and strong

Weak orbicularis oculi and oris,zygomaticus


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Facioscapulohumeral MD

Eventually atrophy involves sternomastoid, serratus,

rhomboid, erector spinae, latissimus and deltoids

Winged and elevated scapulae, prominent clavicles

Popeye arm: upper arm thinner than forearm

Pelvic muscles involved later and milder

Can be asymmetrical

CPK can be normal or mildly elevated Rare cardiac involvement


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Scapular winging

Weak (serratus, lower

trapezius, rhomboids)

stabilizers of scapulacause winging

Scapular angles can be

seen when facing the

patient


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Facioscapulohumeral MD

Foot drop might be seen

Early in the disease weakness can be

asymmetrical

Rare cardiac involvement

CPK normal or slightly elevated


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Scapuloperoneal MD

Autosomal dominant, Chromosome 12

Typically involves muscles of the neck, shoulder,

upper arms, anterior tibial and peroneal groups Onset usually in early or middle adulthood

Walking becomes difficult due to foot drop

Symptoms in arms and shoulders usually seen later

Progression slow in most cases


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Limb-girdle MD

Heterogeneous group Children of both sexes affected

No hypertrophy (besides SCARMD)

Adults can have weakness in either pelvic or shoulder girdle

or both, if later onset more benign course Most commonly heredited as autosomal recessive (2A-2J),

Also AD (1A-1E) forms, AD good prognosis

EMG myopathic, CK normal or only moderately elevated,

cardiac involvement infrequent


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AD Limb Girdle Dystrophies

LGMD 1 Onset is varied from 4-38 years

CPK is slightly or moderately increased

Can have flexion contractures of elbows, ankles, and IPJ

but non-disabling

Slow progression with long periods of arrest

Normal longevity

Some with facial and cardiac involvement

Includes defects in proteins located in myofibril, cell

membrane and EC (collagen proteins)


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AR Limb Girdle Dystrophies

LGMD 2

Affects males and females equally

Shoulder and pelvic girdles affected

Defects in proteins located on cell membranes but also on

myofibril+nucleus (calpain 3)

SCARMD (2C-2F)- clinically similar to DMB, from 3-12 y/o onset,

CPK 10-100 times normal, hypertrophy and joint contractures, rare

cardio involvement

Some have involvement of distal lower extremities (dysferlinopathy)


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Severe Childhood AR Muscular

Dystrophy (SCARMD) LGMD 2C -2E

Calf hypertrophy

Cardiac involvement

marked elevations of CPK early

Defect is in one of the 3 dystrophin associated glycoproteins

sarcoglycan, chr 13q

sarcoglycan is called adhalin, chr 17q21

sarcoglycan also called hetarosin , chr 4q12


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AD Limb-Girdle Dystrophy with

cardiac conduction involvement Mild proximal limb/girdle dystrophy

In half cases cardiac conduction disorders being

the major threat to life Begins in Lext then shoulders

CK normal or moderately elevated

All patients retain ambulation Mild contratures infrequent

Pacemaker required in some old patients


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Emery- Dreifuss Muscular

Dystrophy X-linked, chromosome Xq28 -emerin

Age of onset: childhood- adulthood

Weakness first upper arm and pectoral girdle; later pelvic girdle

and distal muscles in Lexts

Early appearance of contractures in elbow flexors, extensors of the

neck and posterior calf muscles

No pseudohypertrophy

Usually accompanied by severe cardiomyopathy with variable s/aand a/v conduction defects

Death secondary to cardiac problems although general course is

benign in most


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Oculopharyngeal Dystrophy

Autosomal dominant; chr 14q11.2-14q13

Usually late onset (after 45th y/o)

Bilateral ptosis and dysphagia noticed as progressive

difficulty in swallowing and change in voice, can

progress to cachexia

External ocular muscles, shoulder and pelvic muscles

can later become weak CK and aldolase might be normal

EMG only altered in the affected muscle


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LGMD

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22213745 Muscular Dystrophy