Duchenne Muscular Dystrophy

Sri Abboy, MD Genetics Department x 4114

Overview
Basic information about Duchenne muscular dystrophy Inheritance Prevalence Symptoms Treatments

Duchenne Muscular Dystrophy

Defect in muscle proteins

absence of dystrophin protein weakens connections between proteins in muscle and cell membrane calcium moves in and out of ruptured cell membrane as calcium moves into muscle cell, it causes contraction at damaged site and muscle fibers break If severe enough, muscle will begin to waste away

Death of muscle tissue

Progressive muscle weakness

Where is the Gene?

Inheritance

Mother carries the recessive gene and passes it to her child Trait is usually expressed in males

DMD Pedigree

The X chromosome carrying the disease-causing mutation can be tracked through the family. Note: Shaded squares = affected males: dots in circles = carrier females.

Inheritance

XX

XY

XX
Normal female

XX
Carrier female

XY
Normal male

XY
Affected male

Prevalence of DMD

Affects one in 3500 to 5000 newborn males 1/3 of these with previous family history 2/3 sporadic

due to mutation in mothers egg or early embryogenesis

- mother is a new mutation carrier due to mutation in her mothers egg or fathers sperm

Symptoms of DMD

Delayed developmental milestones Loss of motor skills

Muscle weakness Difficulty climbing stairs or hills Difficulty rising (Gowers sign)

Characteristic gait
Calf hypertrophy Clumsiness/frequent falls

Difficulty walking/running

Gowers sign

Weakness of proximal muscles, especially in lower extremities Patient has to use his hands and arms to "walk" up his own body from a squatting position due to lack of hip and thigh muscle strength

Treatments for DMD

To

improve breathing:
therapy

O2

Ventilator Scoliosis

surgery

Tracheotomy

Treatments

To improve mobility:

Physical therapy
Surgery on tight joints Prednisone Non-steroidal medications Wheelchair

The Beginning of Gene Therapy for DMD

Advances in Gene Therapy

Researches have developed "minigenes," which carry instructions for a slightly smaller version of dystrophin that can fit inside a virus Researchers have also created the socalled gutted virus, a virus that has had its own genes removed so that it is carrying only the dystrophin gene

Problems with Gene Therapy

Muscle tissue is large and relatively impenetrable

Viruses might provoke immune system and cause destruction of muscle fibers with the new genes

Resources

Support groups

Face to face, telephone, internet, chat rooms

Sources of friendship and empathy for persons with MD; Exchange ideas and inspirations http://www.mdausa.org for information about groups in specific regions

MDA

Assist in funding

Wheelchairs and braces Equipment loans and repairs, community programs, summer camps