-SHUCHI JOSHI ARIP :30-2:30

  Muscular Dystrophy (MD) is a group of inherited diseases in which the voluntary muscles progressively weaken overtime.  Heart and other organs can also be affected.  MD affects more than 50,000 Americans.  9 major types:  Duchenne, Myotonic, Becker, Limb-girdle, Facioscapulohumeral, Congenital, Oculopharyngeal, Distal, and Emery-Dreifuss

  Can occur at any age  Most common in young males.  Type is based on what age the individual is when muscular dystrophy appears

  Defects in certain genes  The type of MD is determined by which gene is defective  In 1987, the muscle protein associated with DMD was given the name dystrophin  When the gene fails to produce dystrophin, Duchenne MD occurs Causes

 Duchenne muscular dystrophy

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  1 in 3500 male births  X- linked recessive disease  Early onset often before school age  Begins with proximal muscle weakness around age 4  Progresses to distal muscles, making walking more difficult  Around age 10, most children are in wheelchairs  Some experience cognitive problems ]

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  Asymptomatic at birth - Early gross motor skills ( rolling over, sitting, standing) may be normal or mildly delayed  Poor head control in infancy may be the first sign of weakness  Walking achieved at the normal age - but hip girdle weakness may be seen as early as the 2nd year - waddling gait Clinical features

  Weakness starts in pelvic girdle- Extensor muscles of back affected –  Toddlers may assume a lordotic posture when standing to compensate for gluteal weakness.  Cannot bend forward without falling Clinical features

  Presents – 2- 4 yrs  Frequently falls, has difficulty getting up, climbing stairs or getting in and out of a car  An early Gower’s sign is often evident by age 3 yr and is fully expressed by age 5 or 6 yr

 Gets up climbing up his legs- Gower’s sign

  Enlargement of the calves (pseudohypertrop hy) and wasting of thigh muscles is a classic feature.  Next most common site of muscular hypertrophy - tongue, forearm.

  Pseudohypertrophy also seen - triceps, quadriceps  Pseuhypertrophy of muscle fibers - i nfiltration of muscle by fat, and proliferation of collagen.  Fasciculations of the tongue do not occur.

 Pseudohypertrophy seen in supra, infraspinatus, deltoids – Valley sign 15

  Hypertrophy of calf muscles with tightening of tendo achillis- Toe walking  By 8 yrs –walking becomes difficult  Knee jerks disappear early but ankle jerk may be preserved  Positive valley sign Clinical features

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Clinical features cont.  By 12 yrs – wheel chair bound –  Loss of lordosis - lose stabilization of spine ↓ Tendency to tilt to one side ↓ Develop– Scoliosis ↓ Bunching of ribs leads to Esophageal reflux with acute esophagitis, hematemesis, aspiration pneumonitis 18

Clinical features cont.  Intellectual impairment in all  % - IQ < 70  Contractures most often involve the ankles, knees, hips, and elbows.  Cardiac muscle may be affected – Cardiomyopathy  Die by 18 yrs – respiratory failure, pneumonia, aspiration, heart failure 19

  The function of distal muscles is usually well preserved - child can continue using eating utensils, a pencil, and a computer keyboard.  Respiratory muscle involvement - weak and ineffective cough, frequent pulmonary infections  Pharyngeal weakness - episodes of aspiration, nasal regurgitation of liquids, and an airy or nasal voice quality  Extraocular muscles - well preserved

  Death occurs usually at about 18 yr of age.  The causes of death are respiratory failure in sleep, intractable heart failure, pneumonia, or occasionally aspiration and airway obstruction

Laboratory findings  Serum creatinine phosphokinase (CPK)  even in presymptomatic stages, including at birth > 10,000 units ( range 15,000 – 35,000 IU/L) Normal level < 160 IU/L  Other lysosomal enzymes of muscles: Aldolase, Aspartate aminotransferase – increased (less specific) 23

  Electromyography (EMG) shows characteristic myopathic features : amplitude and duration of MUAP decreased, polyphasic potentials  Nerve conduction velocity- normal, No evidence of denervation EMG

  Diagnostic (Vastus lateralis/ Gastrocnemius) Myopathic changes –  endomysial connective tissue proliferation  Scattered degenerating and regenerating myofibers Muscle biopsy –

Muscle biopsy 26

Others  Cardiac evaluation  CXR  ECG  ECHO 27

  Molecular genetic diagnosis - demonstrating deficient or defective dystrophin by immunohistochemical staining of sections of muscle biopsy

Management  No medical cure or a method of slowing its progression. Multidisciplinary approach:  Exercise – physical exercise, physiotherapy  Dietary – prevent obesity  Orthopedic  Psychological  Education  Genetic counselling 29

  Corticosteroids can slow muscle damage in patients with Duchenne muscular dystrophy.  Phenytoin, procainamide, or quinine may treat delayed muscle relaxation for those with Myotonic MD.  Medications can also be prescribed to treat heart problems in some forms of muscular dystrophy. Medications

  Preservation of a good nutritional state  Adequate calcium intake - to minimize osteoporosis  sedentary children burn fewer calories than active children and depression is an additional factor – these children tend to eat excessively and gain weight – Obesity makes a patient with myopathy even less functional

  Primary focus is on gaining muscular strength and endurance  Aerobic exercise is important in preventing excess body fat, as well as decreasing cardiovascular risk factors  Stretching increases ROM and prevents contractures  For children, exercise activities should be as game- like as possible Benefits of Exercise

Some approaches  Experimental approach – Myoblast transfer therapy  Unproven approach – I/M injection of recombinant dystrophin gene  " minigenes, " which carry instructions for a slightly smaller version of dystrophin 33

  Pulmonary infections should be promptly treated.  O 2 therapy  Ventilator  Scoliosis surgery  Tracheotomy To improve breathing:

  Prenatal diagnosis for women having risk pregnancies - with a family history of muscular dystrophy.  Identification of dystrophin gene axon deletions in a male fetus - Couples may elect to terminate the pregnancy if the fetus is affected. GENETIC COUNSELLING

  This disease was first described by Becker and Klener in 1955  X-linked recessive  Late onset – ambulatory till late adolescence  Calf pseudohypertrophy, cardiomyopathy, increased CPK are similar to DMD  Learning disabilities are less Becker muscular dystrophy

  Initially experience difficulties between 5-15 years  Becker patients ambulate beyond 15 years  Majority of patients survive into 4 th or 5 th decade

  X-linked disorder characterized by :  contracture at elbow, ankle and neck,  Cardiomyopathy  Conduction disturbances  Progressive weakness  Proximal U.L. Weakness (scapulohumeral)>Distal L.L. (peroneal)  CPK levels moderately elevated EMERY DREIFFUS MUSCULAR DYSTROPHY

  Weakness in limb girdle distribution with sparing of facial, extra ocular and pharyngeal muscles.  Spared mentation  Calf hypertrophy uncommon  Cardiomyopathy less predictabe LIMB GIRDLE MUSCULAR DYSTROPHY

  Facial, shoulder girdle, proximal arm muscles involved  Patient can’t close eyes forcefully, whistle or hold air in oral cavity  Scapular winging  Foot drop- weak anterior tibial muscles  No hypertrophy  Less pelvic girdle involvement  Sensorineural hearing loss  Cardiac ms, mentation –spared  CPK levels- mildly elevated  EMG- neurogenic picture FASCIOSCAPULOHUMERAL DYSTROPHY

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