Duchenne Muscular Dystrophy

BRIAN CHANDA CHILUBA Dip.PT; Cert. NDT NEUROLOGY CLASS PRESENTATION

Overview

Basic information about Duchenne muscular dystrophy Inheritance Prevalence Symptoms Treatments

What Is Duchenne Muscular Dystrophy?(1)

Genetic Progressive muscle weakness Defects in muscle proteins Death of muscle tissue

MUSCULAR DYSTROPHY
Muscular dystrophies - group of genetic conditions

characterized by progressive muscle weakness and wasting

(atrophy) 20 different types of muscular dystrophy exist (DMD) is named after the French neurologist Guillaume Benjamin Amand Duchenne (18061875), who first described the

disease in 1861

DMD
(DMD) is a severe recessive X-linked form of muscular

dystrophy characterized by rapid progression of muscle

degeneration, eventually leading to loss of ambulation and death DMD is caused by a defective gene for dystrophin (a protein in the muscles) or by mutations in the dystrophin gene, which is located on the X chromosome

DMD
DMD absence of the dystrophin protein weakens the

connections between all of the proteins in the muscle and the cell
membrane cell membrane becomes weaker and ruptures particles, such as calcium, can move in and out of the ruptured cell membrane

Where is This Gene?

PHYSIOLOGY OF DYSTROPHIN
The dystrophin molecule anchors the cytoskeleton of muscle cells to the extracellular matrix, via the dystrophin glycoprotein complex. This includes the sarcoglycans (mutations in which cause limbgirdle muscular dystrophies) and dystroglycans. Muscle cells that lack dystrophin are mechanically fragile, and fail after a few years, hence progressive muscle weakness.

Duchenne Muscular Dystrophy Inheritance(1)

Mother carries the recessive gene and passes it to her child

Trait is usually expressed in males only

Prevalence of DMD(1)

Affects one in 3500 to 5000 newborn males

1/3 of these with previous family history

2/3 sporadic

Symptoms of DMD(1)

Symptoms usually appear before age 6 Delayed developmental milestones Loss of motor skills Characteristic gait Calf hypertrophy Clumsiness/frequent falls

More Symptoms of DMD(1)

Muscle weakness Difficulty climbing stairs or hills

Difficulty rising (Gowers sign)

Difficulty walking/running

GOWERS SIGN

PROGNOSIS
Duchenne muscular dystrophy leads to
quickly worsening disability. Death

usually occurs by age 25, typically from

lung disorders

Treatments for DMD (1)

To improve breathing:
O2

therapy

Ventilator Scoliosis

surgery

Tracheotomy

Treatments (cont.) (1)

To improve mobility:

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

PHYSIOTHERAPY TREATMENT
AIM TO : minimize the development of contractures and deformity by developing a program of stretches and exercises where appropriate anticipate and minimize other secondary complications of a physical nature monitor respiratory function and advise on techniques to assist with breathing exercises and methods of clearing secretions

The Beginning of Gene Therapy for DMD (2)

Advances in Gene Therapy(3)

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(3)

Muscle tissue is large and relatively impenetrable

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

COMPLICATIONS
Cardiomyopathy Congestive heart failure (rare) Deformities Heart arrhythmias (rare) Mental impairment (varies, usually minimal) Permanent, progressive disability Decreased mobility Decreased ability to care for self Pneumonia or other respiratory infections Respiratory failure

References:
1. Muscular Dystrophy PowerPoint by Katherine Kolor, PhD, MS, CDC Ambassador Program, June 2005. 2. Pobojewski, S. The University Record, November 9, 1998. U-Ms improved viral vector delivers dystrophin gene to mouse muscle without major immune Response [online]. 1998. [cited 2005 June 26]. Available at URL: http://www.umihc.edu/~urecord/9899/Nov09_98/12.html 3. Journey of Love: A Parents Guide to Duchenne Muscular Dystrophy [online]. 2004. [cited 2005 June 22]. Available from URL: http://www.mdausa.org/publications/journey/5.html 4. Dictionary.com. Lexico Publishing Group, LLC. [online]. 2005. [cited 2005 June 22]. Available from URL: http://dictionary.reference.com/