Duchenne Muscular Dystrophy (DMD) is the commonest of all muscular dystrophies due to defects in the X chromosome.
Xp21 on X chromosome
1: 3500 male birth
X-Linked recessive transmission; So only in BOYS (or in girls with sex chromosome disorder)
Failure to code in the dystrophin gene
Dystrophin gene: Required for the stability of cell membrane of cardiac and skeletal muscles
Clinical Features of Duchenne Muscular Dystrophies
Symptoms began at the age of 3-6 years with insidious onset
Key role: Diagnosis of disease early birth of another affected child can be avoided
Proximal muscle is affected first than distal (Glutei, quadriceps, tibialis anterior)
Wide-based stance and gait
Foot: Equinus
Pelvic: Anterior tilt
Lordotic Spine
Extended neck
Calf muscle: Bulky ( Replacement of fat -> Psuedohypertrophy)
Difficult in standing and climbing: Can’t run properly=Frequent falls
Grower’s Sign: The child climbs up supporting his own leg due to Gluteus Maximus and thigh muscles
Upper limb weakness follows around 3-5 years
At 10 years child becomes dependent on a wheelchair, rapid deterioration of spinal posture (Scoliosis)
At < 30 years: Cardio-pulmonary failure is the Cause of Death
Laboratory:
Increase excretion of creatine
Decrease creatinine in urine
Creatine: Synthesize from glycine and other amino acids in the liver and is deposited in muscle
Creatinine: Arises from muscle creatine due to loss of phosphate from creatine phosphate
When the muscle is destroyed: It is less capable of storing creating= excreated rather than converting to creatinine
Normal :
- Creatinine excretion: 22 mg/ kg/ 24 hr
- Creatine excretion: 2-3 mg/kg/24 hr
Serum enzymes
Elevation of serum aldose and creatine phosphokinase (diagnostic of myopathy)
[ Creatine phosphate (Increase in skeletal muscles) is more specific than aldolase]= Also found in nonmuscular sites (Liver and blood cells)
24-hour urinary creatine excretion
For a quantitative assessment of the progression of the disease
Electromyographic Studies
Individual motor unit potential decreases in size during voluntary contraction and the number and rate of unit firing increase
Genetic testing
DNA polymerase chain reaction
Muscle Biopsy
Tissue obtained from the weakest accessible muscle
< 50% strength : More likely to give (+) biopsy
Vastus lateralis: Most common muscle biopsy
Dystrophin analysis can be done
Pathology
Gross Appearance:
- Enlarged gastrocnemii: Fatty tumors (not like muscles)
- Other muscles are small: Color varies from yellowish to pinkish-gray
- Pale translucent appearances: Resembling fish flesh
- Depends upon the relative amount of fat/ fibrous tissue
- Which replaces muscle fibers
Microscopic Appearance:
- Loss of muscle fibers due to segmental necrosis
- Subsequent fragmentation of fibers
- Necrosis:- Phagocytosis and proliferation of histocytes in these zones
- Sacrolemma nuclei: Enlarged
- Increase interstitial connective tissue
- Infiltration of fatty/ adipose tissue
- Heart: Myocardial fibrosis
Treatment Options:
Duchenne Muscular Dystrophies treatment is explained below
No definite treatment : Ultimate fatal
Principle :
Achieving stabilization and balance so as to enable the patient to ambulate independently or with little support for a long period
Medical Therapy:
Corticosteroids:
- Their anti-inflammatory action can help in preserving muscle strength and increase the duration of ambulation
- Side effects: Osteoporosis, Risk of fractures, Cataracts
Glutamine and creatine have mixed responses but are well tolerated
Aminoglycosides (Eg. Gentamycin):- Also shows improvement in muscle power — where defects are due to stop codon
Physical and Surgical Therapy
Maximize the duration of ambulation and prevent complications of immobilization:- Once the child loses the power to move independently
Instructions for exercises, stretching, and walking with crutches
Contracture of the lower extremity frequently develops at an early age; especially in the calf muscle, tensor fascia lata, iliotibial band, and equinus deformity of the foot associated with some flexion deformity of hip, Knee, lumbar lordosis
Contracture must be treated at an early stage by stretching and splinting at night
If contracture progresses: Surgical correction may be necessary
Heel cords
Released by subcutaneous tenotomies and toe to groin cast applied with knees in extension and the ankles in 10-degree dorsiflexion
Following this procedure: Patient no longer can stabilize knee provided by fixed plantar flexion of feet
Consequently, the long brace may be worn
Tight iliotibial bands
Released by Yount’s Procedure
The large rectangular segment of the band to the corresponding intermuscular septum removed
The hip and knee show maximum flexion contracture
Posterior tibial Muscle
Always retain considerable power for long periods
Can be transferred by interosseous route to 3rd cuneiform to reinforce dorsiflexion
Postoperatively: Patients are immediately allowed to walk, if necessary with a walking cast
Followed by bracing
Because immobilizing these patients rapidly weakens them
Management of Scoliosis
Curve progression occurs: Can be up to 90 degrees
Previously: To retards the progression of scoliosis plastic jacket/corset was used but is avoided nowadays
No role in the prevention of curve progression but further decreases the pulmonary function
If scoliosis is marked ( > 30 degrees): Instrumentation and spinal fusion are advised which maintain pulmonary function and improve quality of life
But if the life span is < 2 years: Spinal surgery is contraindicated
Gene therapy: Dystrophin in the form of myoblast is introduced: Have not been successful in humans
Details on Scoliosis
