muscular dystrophy. an overview

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An overview on Muscular dystrophy

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Page 1: Muscular dystrophy. an overview
Page 2: Muscular dystrophy. an overview

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.

Page 3: Muscular dystrophy. an overview

Etymology

Greek term –Dystrophy

Dys - Aberrent

Trophy-Nourishment (Aberrant growth or nutrition of muscle fibers)

Page 4: Muscular dystrophy. an overview

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.

Page 5: Muscular dystrophy. an overview

Incidence

Mostly affects boys (rarely girls)

1 in 35000 male births (DMD)

5.4 IN 100,000 MALE BIRTHS (BMD)

Page 6: Muscular dystrophy. an overview

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.

Page 7: Muscular dystrophy. an overview

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.

Page 8: Muscular dystrophy. an overview

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

Page 9: Muscular dystrophy. an overview

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.

Page 10: Muscular dystrophy. an overview

TYPE GENETICS

AGE OF ONSET

INVOLVEMENT PROGRESSION

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

Page 11: Muscular dystrophy. an overview

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.

Page 12: Muscular dystrophy. an overview

DUCHENNE MDEarly 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.

Page 13: Muscular dystrophy. an overview

GOWER'S SIGN

Page 14: Muscular dystrophy. an overview

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.

Page 15: Muscular dystrophy. an overview

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.

Page 16: Muscular dystrophy. an overview
Page 17: Muscular dystrophy. an overview

BECKER MDMilder 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.

Page 18: Muscular dystrophy. an overview

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

Page 19: Muscular dystrophy. an overview

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.

Page 20: Muscular dystrophy. an overview

FASCIO-SCAPULOHUMORAL MD

-Menifest around puberty.-Involvement of facial,shoulder and proximal arm muscle.-Winging and elevation of scapulaeoccur.

-Footdrop occur.-Hypertrophy does not occur.-Progress of weakness is slow.-Pelvic-girdle involvement lateand less.

-Cadiomyopathic and neurogenic changes occur.

Page 21: Muscular dystrophy. an overview

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 Polyneuritis3 Warding Haffman disease. 4 Endocrine myopathies.5 Glycogen storage disease of muscle.6 Poliomylities.7 Cerebral palsy etc.

Page 22: Muscular dystrophy. an overview

SCREENING AND DIAGNOSISLab 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.

Page 23: Muscular dystrophy. an overview

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

Page 24: Muscular dystrophy. an overview

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.

Page 25: Muscular dystrophy. an overview

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.

Page 26: Muscular dystrophy. an overview

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

Page 27: Muscular dystrophy. an overview

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).

Page 28: Muscular dystrophy. an overview

COPING SKILLS

Page 29: Muscular dystrophy. an overview

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