Muscular Dystrophies

1. Muscular Dystrophies Lhedaven C. Santos R.N.

2. 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 it’s protein product

3. 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 proteins known as dystrophin associated proteins (DAP)

4. Etiology • Loss of dystrophin leads to disruption of the dystroglycan-protein complex rendering the sarcolemma susceptible to breaks during contraction • These defects are shown to allow ingress of EC fluid and calcium which activate proteases and cause protein degradation • Leakage of CK into serum is then seen

6. 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)

7. 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

8. 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

9. 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

11. Gower’s maneuver • 4 point position • Hands up to thigh alternately

12. 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 DTR’s are lost • Bones are thin and demineralized • Can have mild mental retardation • Although smooth muscle is usually spared heart is usually affected

13. 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

15. 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 Duchenne’s 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

16. 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

17. 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

18. Scapular winging • Weak (serratus, lower trapezius, rhomboids) stabilizers of scapula cause winging • Scapular angles can be seen when facing the patient

19. Facioscapulohumeral MD • Foot drop might be seen • Early in the disease weakness can be asymmetrical • Rare cardiac involvement • CPK normal or slightly elevated

21. 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

23. 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

24. 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)

25. 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)

28. 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/a and a/v conduction defects • Death secondary to cardiac problems although general course is benign in most

30. 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