MUSCULAR D

YSTR

OPHY

Midhun Paul

Monalisa

Simson

WHAT IS DUCHENNE MUSCULAR DYSTROPHY?

DUCHENNE MUSCULAR DYSTROPHY IS A GENETIC OR HEREDITARY MUSCLE CONDITION; CHARACTERIZED BY PROGRESSIVE SKELETAL MUSCLE WEAKNESS, DEFECTS IN MUSCLE PROTEINS, AND THE DEATH OF MUSCLE CELLS AND TISSUE.

FUNCTION OF DYSTROPHIN

Dystrophin provides strength to muscle cells by linking the internal cytoskeleton to the surface membrane.

Without this structural support, the cell membrane becomes permeable. As components from outside the cell are allowed to enter the internal pressure of the cell increases until the cell bursts and dies.

HOW MUSCULAR DYSTROPHY IS CAUSED?????

In DMD, absence of the dystrophin protein weakens the connections between all of the proteins in the muscle and the cell membrane.

Eventually the cell membrane becomes weaker and ruptures.

As a result, particles, such as calcium, can move in and out of the ruptured cell membrane.

As calcium moves into the muscle cell, it will cause contraction at the damaged site and muscle fibers will break. When this is severe enough, the muscle will begin to waste away

It is due to mutation of a gene, responsible for production of dystrophin

The DMD gene is located on the Xp 21 band of the X chromosome

Mutations leading to the absence of dystrophin

WHERE IS THIS GENE??????

DUCHENNE MUSCULAR DYSTROPHY INHERITANCE

During the translocation process, a mutation occurs.

Mutations leading to the absence of dystrophinVery Large Deletions (lead to absence of dystrophin)

Mutations causing reading errors (causes a degraded, low functioning DMD protein molecule)

Stop mutationSplicing mutationDuplicationDeletionPoint Mutation

TO WHOM IT WILL BE EFFECTED

Mother carries the recessive gene and passes it to her child

Trait is usually expressed in males only

WHAT ARE THE SYMPTOMS????• Muscle weakness• Delayed development of muscle motor skills• Problems walking (delayed walking)• Difficulty using one or more muscle groups

(depends on the type of dystrophy)• Eyelid drooping (ptosis)• Drooling• Hypotonia • Mental retardation ( only present in some types of

MD)• Joint contractures (clubfoot, clawhand or others)

• Onset : age 3-6 years

• Progressive weakness

• Pseudohypertrophy of calf muscles

• Spinal deformity

• Cardiopulmonary involvement

Mild - moderate MR

DMD: Clinical manifestation

Pseudohypertrhophy of calf muscle, Tip toe gaitforward tilt of pelvis, compensatory lordosis

Laboratory TestMuscle biopsy: the primary test used to confirm the diagnosis. DNA test Serum CPK (creatine phosphokinase-an enzyme found in muscle)

may be elevated. EMG (electromyography) may confirm that weakness is caused by

destruction of muscle tissue rather than damage to nerves. ECG (electrocardiography) to monitor changes in cardiac status

Myoglobin - urine/ serum:    When muscle is damaged, the myoglobin is released into the bloodstream. It is filtered out of the bloodstream by the kidneys, and eliminated in urine. In large quantities, myoglobin can damage the kidney and break down into toxic compounds, causing kidney failure.

LABORATORY DIAGNOSIS

LDH:   LDH is most often measured to evaluate the presence of tissue damage. The enzyme LDH is in many body tissues, especially the heart, liver, kidney, skeletal muscle, brain, blood cells, and lungs.

Creatinine : A normal (usual) value is 0.8 to 1.4 mg/dl.  Creatinine is a breakdown product of creatine, which is an important constituent of muscle. A serum creatinine test measures the amount of creatinine in the blood.  Greater-than-normal levels may indicate: Muscular dystrophy. Lower-than-normal levels may indicate: Muscular dystrophy (late stage)

AST: The normal range is 10 to 34 IU/L. An increase has many indications, one of them being progressive MD.

FACTS ABOUT MUSCULAR DYSTROPHY

DMD affects mostly males at a rate of 1 in 3,500 births.

There are over 200 types of mutations that can cause any one of the forms of muscular dystrophy.

DMD is the most severe and common type of muscular dystrophy.

DMD is characterized by the wasting away of muscles.

DMD is the most aggressive form of muscular dystrophy.

Diagnosis in boys usually occurs between 16 months and 8 years.

Parents are usually the first to notice problem. Death from DMD usually occurs by age of 30