An overview on Muscular dystrophy

2. Objectives
 Objectives of this presentation is to share following aspects of
Muscular dystrophy:
 Etymology, Definition and Incidence.
 Causes and Pathogenesis
 Types.
 Clinical features of different types.
 Screening and diagnosis.
 Management.

3. Etymology
 Greek term –Dystrophy
 Dys - Aberrent
 Trophy-Nourishment (Aberrant growth or nutrition of
muscle fibers)

4. Definition
There is no single disease called MUSCULAR DYSTROPHY .The term
designates a group of genetically determined progressive, primary
disorders of muscle that vary in inheritance pattern. Age of onset,
initial muscle attacked and the rate of progression.

5. Incidence
 Mostly affects boys (rarely girls)
 1 in 35000 male births (DMD)
 5.4 IN 100,000 MALE BIRTHS (BMD)

6. Causes
 Genetic deficiency of the muscle protein Distrophin.
 Inherited defective gene.
 New mutation in a gene rather than an inherited defective gene.
Distrophin:
 Primary product of DMD gene.
 High molecular weight cyto skeletal protein.
 Occurs in skeletal muscle ,smooth muscle, brain, peripheral nerves
and several other tissues.

7. Pathogenesis
As muscular dystrophy is a genetic disorder with deletation mutation
affecting the xp 21 region on short arm of X chromosome, distrophin
encoded by this genelocus, is absent. Distrophinis apart of large
complex of sarcolemmal protein and glycoprotein and lack of
distrophin leads to osmotic fragility of muscle fiber.

8. Muscle fibres become more succeptible to damage
Sarcolemma damage
Leakage of creatinine kinase
Take of excess calciam
Cause further damage
Necrosis of muscle fibres (voluntary muscles initially)
Phagocytosis of degenarating fibres
Replacement of small muscle fibres which are rich in fat and connective
tissues
Interstitial fiborsis(contracture formation)
Finally involvement of other organs and involuntary muscles
MUSCULAR DYSTROPHY

9. TYPES
Each type of muscular
dystrophy is a distinct entity
having difference in inherita-nce
pattern, age of onset,
clinical features, other
system
involvement and clinical
course.

10. TYPE GENET
ICS
AGE OF
ONSET
INVOLVEMENT PROGRESSI
ON
Duchenne's XR 2-5 years Pelvic girdle Fast
Beker's XR 8-10 years Pelvic girdle Slow
Emery-
Driefuss
XR/AD 5-15 years Biceps,tirceps and peroneal muscles Slow
Limb-girdle AR/DR 10-30 years Pelvic/shoulder girdle Slow
Congenital AR Newborn
period
Generalized Slow
Distal AR/DR 12-30 yeare Gastronemius slow
Fascio-
Scapulo-
Humoral
AD Adolescent Face,shoulder and upper arm Variable
Myotonic
dystrophy
AD Newborn
period-adult
Face,sternocledomastoidand girdle
muscle
slow

11. CLINICAL FEATURES
-Vary according to the type of muscular
dystrophy.In general they may
include:-
-Muscle weakness.
-apparent lack of coordination.
-Progressive creeping,resulting in
contracturesof musclesadn loss of
mobility.
C/F OF DIFFERENT TYPE OF M.D.
Dystrophies-These type of M.D. are due
to genetic deficiency of muscle protein
DYSTROPHIN viz.
*Duchenne M D.
*Becker M.D.

12. DUCHENNE MD
Early menifestations-
1.First sings appear around age 2-5 years.
2.The child may appear clumsy while walking.
3.Tiptoe walking and frequent falls.
4.Waddling gait with a compensatory lumbar
lordosis.
5.Difficulty in getting up from lying or sitting
position.
6.Difficulty in climbing up stairs and raise the
hand above the shoulder or comb the hair.
7. Hypertrophy of calf muscle(at 4-5 years).
Gowers sign:-It is early common sign of
M.D.To get up from the ground,the child WALK
up his thighs with his hand.
It indicates weakness of pelvic girdle muscle.

13. GOWER'S SIGN

14. Late menifestation
1.Problem get steadily worse over the next several years.
2.Muscle weakness first affect feet,front of
thighs,hips,belly,shoulder and elbow, later it affects
hand,face and neck muscle.
3.Tendon reflexs are sluggish or absent.
4.Development of contactures.
5.Most children become unable to walk by age 10.
6.Wheel chair dependancy occurs by age 12.
7.Also develop severe curve of spine.
8.Other system involvement-
*Cardiac involvement-(Fibrosis– posterio-basal portion of left
ventricular walls)-
-onset usually after the age of 10 years.
-Cardiomyopathy develops(almost all patient) beyond the age
of 18 years.
-Congestive cardiac failure and arrythmias.
-In 10% cases death occur due to cardiac dysfunction.

15. Respiratory involvement:-
-Resiratory muscle weakness including diaphragm.
-pulmonary insufficiency and resp. infection(pneumonia).
-Death at about late teens or early 20‘s.
GIT involvement :-
-Acute gastric dilatation(Intestinal pseudo obstruction)
-Sudden episode of vomiting with pain and distension.
-Leads to death .
Nervous system involvement:-
-The mean IQ is 80.
-1/3 of children having IQ below 75.
-25% of frank mental defect.

17. BECKER MD
Milder form of dystrophinopathies.
-Generally affect older boys and young men.
-Early onset-between age 5-15.
-Although an onset in third and fourth decade or
even later can occur.
-Patient ambulate beyond age 15 and often well
into adulthood.
-Progresses more slowely usually over several
decades.
-s/s of BMD are similar to those of DMD.
EMERY-DRIEFUSS M.D.-
-Usually begins at shoulders, upper arm, shins
etc.
-Contractures develops at
elbow,ankle,neck,spine etc.
-Cardiomyopathy,cunduction disturbance.
-Begin at childhood to early teen years and
progresses slowly into adult life.

18. LIMB- GIRDLE MD(LGMD)
-Caused due to sacroglycanopathies.(mutation in
sarcoglycan gene)
-First demonstrate weakness in limbs,girdle(pelvic-pectoral)
muscle.
-Gradually involves facial,extraocular and
pharyngeal muscle.
-Calf hypertrophy present.
-Cardiomyopathy less predictable.
-Progress slowly from early childhood to adulthood.
- DISTAL MD-
-Involvement of muscles farthes away from centre
of body.
-Muscles of hand,forearm,feet and lower leg.
-less severe and slow progress.
-begin in adulthood between the age of 40 and60

19. CONGENITAL MD
-At birth or first few weeks of birth.
-Hypotonia and proximal muscular weakness(non-progressive).
-Most affected children eventually may able to stand with
support or few learn to walk.
-Joint contractures develops.
-CNS involvement is prominent.
-(Muscle biopsy:-marked elevation oin endomysial and
perimysial connective tissue.
Western blot:- deficiency of merosin.
MRI:- white matter change.
Chorionic villous material for prenatal diagnosis)
Fukuyama CMD- in Japenese, Dutch,German children.
-associated with cardiomyopathy,mental
retardation,seizures and growth failure.

20. FASCIO-SCAPULOHUMORAL MD
-Menifest around puberty.
-Involvement of facial,shoulder and
proximal arm muscle.
-Winging and elevation of scapulae
occur.
-Footdrop occur.
-Hypertrophy does not occur.
-Progress of weakness is slow.
-Pelvic-girdle involvement late
and less.
-Cadiomyopathic and neurogenic
changes occur.

21. MYOTONIC DYSTROPHY
-Multisystem disorder(cardiac,CNS,endocrine,etc).
-Muscular weakness with myotonia.
-Neonate has tented upper lips,difficulty in sucking and swallowing.
-Generalized hypotonia
-Respiratory distress.
-Delayed motor development.
-Mental retardatiopn.
-Immunodeficiancy.
Other symptoms- ptosis, opthalmoplegia, cardiac conduction
disturbance, dysphagia, aspiration, constipation, diarroea, etc. also
frontal balding in men, mild diabetes.
Differential Diagnosis-
1 Myopathies.
2 Polyneuritis
3 Warding Haffman disease.
4 Endocrine myopathies.
5 Glycogen storage disease of muscle.
6 Poliomylities.
7 Cerebral palsy etc.

22. SCREENING AND DIAGNOSIS
Lab diagnosis-
Blood test- serum CPK level- elevated upto
15000-20000 U/l(20-100 times
higher than normal).
Level may reduce in advance disease.
Detection of CPK can diagnose 2/3 carrier female.
Electromyography(EMG)- Decreased amplitude and duration of motor
unit potential.
-Increased frequency of polyphasic potential
.
Histopathology(muscle biopsy)
-Muscle fibres shows diffuse changes of degeneration and regeneration.
Immunohistochemistry- Dystrophin deficiency and mutation analysis on
peripheral blood leukocytes.
Gene testing- By multiplex PCR for gene detection.

23. MANAGEMENT
There is currently no defenative
treatment.But such a management can
be designed which help to prevent the
contractures, reduce the deformities
and allow the patient to remain mobile
as long as possible.Treatment may
include-
1. Various type of physiotherapy
2. Medication
3. Assistance devices
4. Surgery
5. Gene therapy

24. 1.PHYSIOTHERAPY
-Encourage ambulation with various type of physiotherapy, exercise
and daily walking.
-Exercise-*Stretching - 20 min. twice daily to prevent contractures.
* Walking - to provide regular range of motion of joint
and prevent contractures.
*Respiratory -as shouting climbing and breathing exercise.

25. 2.MEDICATION
- Myotonic MD- Mexiletine,Phenytoin,Carbamezapine, Quinine and
procanamide etc. may be used to treat delayed muscle relaxation.
- Duchenne MD-
-The only useful drug is prednisolon(to improve muscle strength
and delayed progression).
-Dose-0.75mg/kg/day for 10 days every month.
- Continue the drug as long as child is ambulatory.
-Another drug-Oxandrolone-0.1mg/kg/day for 3 months.(synthetic
testerone derivative)
-Other symptom-
1-Cardiomyopathy, CCF (conventional management)
2-Respiratory disorder- antibiotic therapy for infection.
-To vaccinate for pneumonia and H.
influenzae.
-Newer modalities- Delfazacort, albuterol, creatine,
gentamycin,calciam channel blocker and Q 10 can be used.

26. 3.ASSISTIVE DEVICES
a) Braces-To provide support for weak muscle.
-To keep muscle tendon stretched and flexible.
-For slowing the progression of contracture.
.
b)Canes, walker and wheelchairs- To maintain mobility and independence

27. c) Splints, sand bags etc- To keep patient walking better by ankle splints.
-Sand bags will help to press down the legs and help strengthen them if the
contractures of hip and knees begin to develop.
4. Surgery-a)
Tendon realease surgery – To relieve tendons of hip, knees and achillies so as release
the developed contractures.
-Surgery to correct the curvature of spine (scoliosis).

28. COPING SKILLS

29. T
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