Dystrophy progressive muscular (DMP)


I- Introduction :

  • The DMP are a group of hereditary pathology of various etiologies and variable course.
  • They affect the muscles that have reached maturity and have structural common denominator the dystrophic appearance clearly shown on histological examination of a tissue sample muscle.
  • They are expressed clinically by a deficit in muscle strength associated with atrophy topography usually proximal

II- History and succession classifications :

Before Father of genetics, DMP classification was based on clinical symptoms and transmission mode.

Recent advances made in genetics have allowed a new precise classification, based on cell pathophysiology and the identification of genes and / or pr- involved.

III- pathologic study :

The DMP have as a common denominator the & rsquo; dystrophic appearance characterized:

  • L & rsquo; irregularity of muscle fiber size (FM).
  • Necrotic fibers.
  • Fiber regeneration.
  • Proliferation of fatty tissue that replaces the muscle tissue

IV- Description of different types of WMD :

A- Les dystrophinopathies :

1- Clinical description of dystrophinopathies :

  • They are represented by Duchenne de Boulogne (DMD) and Becker (BMD). They are gonosomal transmission (Only boys are affected)
  • They are the leading cause of myopathy in the male child, They are linked to a quantitative abnormality and / or qualitative dystrophin.
  • Dystrophin is a Professor- from 427 KD a, made of 3685 AA, encoded by the DMD gene, which consists of 79 exons. D s & rsquo; d & rsquo acts; a Pr- ubiquitaire (skeletal muscle, the heart, smooth muscle and brain), topography : under membrane

Description of Duchenne de Boulogne (DMD) :

early age
  • very early, from the antenatal period.
  • usually between 3-4 years
  • No pathological manifestation is present at birth especially not hypotonic.
Between 3-6 years
  • On delayed with a tendency to move on tiptoe.
  • Difficulty running, jump, to go upstairs.
  • Falls are common.
  • The motor deficit predominates on the muscles of the pelvic girdle subtrochanteric : Gowers (+) with a waddling gait.
  • A lumbar lordosis.
  • The muscles of the shoulder girdle are affected late.
Between 7-10 years
  • gradual increase of the deficit of the pelvic girdle- trochanteric and glenohumeral extending triceps, biceps, the wrist extensors and flexors of the neck.
  • The muscles innervated by cranial nerves are respected.
  • Atrophy of the muscles involved in the motor deficit.
  • Decrease see abolition of deep tendon reflexes.
Between 10-12 years
  • Loss of ambulation.
  • An important step in the evolution of the disease. Often precipitated by infection or surgical episode.
At the age of 20 years
  • All muscles are paralyzed with the exception of finger flexors which retain some strength.
  • Muscles, oculomotor and throat are still intact.
  • Macroglossia discomfort swallowing.
  • Death occurs after respiratory complications decubitus.

2- Other events :

achievement heart: it is almost constant, it causes in DC 10-50% cases. Were especially dilated cardiomyopathy

respiratory impairment: it is early (bronchial congestion. Pneumonia and respiratory failure.

Mental disorders: present in 40 % especially of DMD patients

Description of Becker muscular dystrophy (BMD) :

  • L & rsquo; mean age at onset of BMD is del2 years.
  • it s’ expresses a deficit of pelvic d & rsquo; slow evolution secondarily reaching the shoulder girdle.
  • It may be noted cramps and myalgia.
  • Deep tendon reflexes are preserved long.
  • The loss of walking is between: 14-18 years.
  • Cardiac involvement is possible.
  • IQ is at the limit of normal.

3- Additional examinations of dvstrophinopathies :

a- Determination of muscle enzymes :

CPK et LDH : increased d & rsquo; a constant and major.

b- electromyographic (EMG) : it shows a rich drawn in potential power unit which Y amplitude and duration are reduced.

c- Muscle biopsy : it shows the formula dystrophic, a size irregularity of muscle fibers (FM) with necrosis – regeneration of (FM) and proliferation of fatty tissue.

specific diagnostic means

d- Analysis of dvstrophin : Immunohistochemistry / The Western Blot allow detection of dvstrophine.

At the Duchenne: dystrophy is absent

At the Becker : it is present but its molecular weight is abnormal.

e- genetic study :

The dystrophin gene is altered by 3 types of mutations. deletions are observed in 65 %, duplication in 5 % and point mutations in 30 % cases.

B- Description of muscular dystrophy d & rsquo; EMERY DREIFUSS (SMEs) :

  • Autosomal dominant (AD), autosomal recessive (WITH) and linked recessive & rsquo; X (RLX).
  • Is defined by the triad:
  1. Early retractions especially at the elbow flexors, the sural triceps and posterior muscles of the neck
  2. Weakness and muscle atrophy in early Humeral-peroneal slowly evolving
  3. cardiomyopathy

C- Description myopathies belts :

  • Myopathies belts are a group of neuromuscular disorders very heterogeneous both clinical and genetic
  • They are distinguished by their AD transmission mode or AR.
  • Clinically they manifest by a motor deficit & rsquo; gradual installation 02 belts variable slow evolution, often accompanied by spinal deformities (hyperlodose) and of retractions tendon.
  • The term LGMD is recent (Walton et Natrass 1950). Since 1995 was set by reference to the transmission mode number " 1 "For AD forms and the number" 2 "For forms and AR Locus corresponding classified alphabetically and chronologically

D- Clinical description of myopathy facio-scapulohumeral (FSH) :

  • It is AD transmission whose genetic anomaly has been located since 1990 sur chromosome 4 (4q 35). It begins between 10-20 years
  • As indicated by his name, it is expressed clinically by damage to the muscles of the face, of the shoulder girdle and arms

At the front :

  • L & rsquo; blankness of the face is the essential sign of the beginning
  • Sometimes the facial damage is moderate : difficulty whistling and inflate the cheeks
  • The eyes appear wide open and Highlights : Achievement of orbicular.
  • L & rsquo; complete occlusion of the eyes can not sleep and hang above this sentence is often repeated by the sick "in the family by sleeping with open eyes".
  • Reaching the shoulder girdle is the 1FH reason for consultation, it is early and asymmetric, interested fixator muscles of the shoulder blade.
  • Reaching the upper limbs is late but consistent with normal front arm.
  • The proximal and distal muscles of the lower limbs may be affected

Additional tests :

  • CPK are normal or moderately?!.
  • L'EMG: shows a myogenic plot.
  • Muscle biopsy is not systematic, it shows dystrophic process.
  • L & rsquo; molecular abnormality : reducing the number of repetition of a sequence named D4Z4 (chomosome 4). In normal subjects is repeated 19-96 time. In the patient repeat member is small as low until 1

E- Clinical description of distal myopathies (MD) :

  • They are expressed clinically by motor deficit associated with atrophy affecting distal lower limb muscles and / or higher
  • Diagnosing (MD) is based on :

– The mode of transmission: AR AR
– The age of early onset or late.
– The location of muscle damage: distal, beginner to senior members (mains) or below (feet).

F- Congenital muscular dystrophies (DMC) :

  • The DMC is a group of hereditary muscle diseases and genetically determined transmission AR.
  • They are early revelation, usually from birth or dice them theIrish months of life
  • Their clinical picture is dominated by yn weak muscles of the limbs and trunk, hypotonia and muscle contractures
  • On distingue 3 types de DMC:

– The forms with isolated myopathy
– The forms related to ocular involvement
– The forms related to brain damage

G- Clinical description of muscular dystrophy Oculopharyngeal :

  • rare muscle disorder, de transmission AD
  • It affects 02 sexes with equal frequency, starting at age 50 – 60 years, by muscle weakness resulting in ptosis and swallowing disorders.

H- Clinical description of myotonic dystrophy :

  • multi system involvement, The most common adult DMP, she starts . 20-30 years.
  • De transmission AD
  • it combines : muscular dystrophy, a true myotonia and other organs abnormalities (eye, the nervous system, device cardiorespiratory, digestive and endocrine glands)

1- Clinical description :

a- Achieving the & rsquo; muscular system :

Is translated by :

A true myotonia, muscle atrophy and motor weakness of distal topography.

myotonia :

  • major signs of the disease, it s & rsquo; d & rsquo acts; abnormal painless and slow muscle relaxation with the waning of a voluntary contraction or provoked

It is true: clinique, mechanical and electrical (EMG).

The motor deficit :

  • Achieving the muscles of the face is early and consistent
  • The lifter reaching the upper eyelid : bilateral ptosis
  • Achieving rorbiculaire eyelids: is rare and causes difficulty closing eyes
  • Achieving the masticatory muscles (temporal, masseter and pterygoid) -* hollow cheeks, disorders of mastication, drooping jaw
  • Reaching Muscle pharyngo-laryngeal and tongue - "nasonnée voice.
  • Achieving muscle : sterno-mastoid is neck extensors is late.
  • to members : muscle damage is distal

b- Other clinical manifestations :

camera eye : cataracts, major symptom, it is present in 100% patients after 40 years.
cardiovascular system : 90% of patients have a pathological ECG
Achievement of dander and skin : (baldness 80% male patients)
endocrine events : diabetes, dysthyroidie.

2- Additional tests :

  • CPK – LDH = are normal
  • EMG myogenic with myotonia. The myotonia is as bursts of potential d & rsquo; brief power units, very close dice appear intent of the needle, short course 20-30 seconds, frequency 40-60 Hz. Their amplitude believe Decreased numbers then gradually

genetic study :

Amplifying a CTG triplet in the DMPK gene carried by the short arm of chromosome 19.

V- Supported :

A- specific therapeutic :

The management of the DMP is multidisciplinary.

1- drug therapy :

In dystrophinopathies, corticosteroids are administered orally is right 0,7 mg/kg/j.
He improved muscle strength, decline the age of loss of walking but their very significant side effects make their prescription brief.

2- Genetical therapy :

Involves transferring a normal gene to compensate for a defective gene.
It allows to correct the defective gene in situ.

B- nonspecific therapeutic :

1- Symptomatic treatment :

cardiac : ECG, échocardio, cardiac scintigraphy, heart on hotler 24 hours, conversion enzyme inhibitors are used in 1time intention when decreasing the fraction & rsquo; ejection.

Respiratory : .monitoring lung growth : functional test, 1 once a year and twice yearly when lung function deteriorates.

Orthopedic :

  • prevent joint deformities ;
  • maintain proper functioning of the muscle tissue ;
  • prevent vicious attitudes.

2- Physiotherapy :

  • fight against tendon contractures.

3- Equipment :

  • limit the deterioration of respiratory function ;
  • Allows better seating and reclining facility. To bark

Dr Y's course. suffice – Faculty of Constantine