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Duchenne's Muscular Dystrophy - Coggle Diagram
Duchenne's Muscular Dystrophy
Pathogenesis
Gene for DMD is present on the X chromosome and is recessive
Females are typically carriers of DMD whereas males present with the symtpoms
This is a frameshift genetic mutation that is normally an insertion or deletion of a coded portion of a gene
Atrophy beings in the pelvic and shoulder regions, but as the disease evolves other muscle areas like the trunk or forearms
If the disease affects the trunk it can eventually lead to deterioration of the heart and respiratory muscles which can become detrimental to one's health
As some muscle groups are atrophied, the calves appear larger than normal
Atrophy and wasting of voluntary muscles commonly occurs first and leads to decreased mobility
Atrophy in the gastrointestinal region can result in either constipation or diarrhea as the muscles of the digestive tract suffer from discoordination and slower movements
Occurs due to mutations in the gene that makes cytoskeletal protein dystrophin (427-kDa gene)
With a diminished dystrophin supply, the dystrophin-associated protein complex is unstable, which can lead to fiber damage and membrane leakage
This makes the sarcolemma of muscle cells weaker due to lack of the dystrophin protein production and circulation
Patients who have DMD lack enough of the dystrophin protein in their bodies, so the cytoskeleton isn't able to be linked to the extracellular matrix
There are considered to be 5 stages associated with the progression of DMD
Diagnosis (infancy/childhood)
Early ambulatory (childhood)
Late ambulatory (late childhood/adolescent/young adult)
Early non-ambulatory (adolescent/young adult)
Late non-ambulatory (adult)
Clinical Manifestations
Walking on toes or a waddling gait
Eventually the ability to walk may be lost
By 10-12 years old, a wheelchair is typically necessary
From around age 8, leg braces may be required to ease the activity of walking
Due to tight tendons and ligaments in the heel that cause it to become raised
Delayed growth and development of muscles
Frequent falls and difficulty with stairs
Delayed movement from or to a sitting or standing position (known as Gower's sign)
Wasting or atrophy of muscles due to weakness
Enlarged calf muscles (due to fat in the calves, not muscle)
Potential dyshagia
By age 3 there are signs that point to DMD in affected individuals
Respiratory problems and difficulty breathing occur due to lack of strength in the diaphragm, inspiratory, expiratory, and accessory breathing muscles
Reduced bone density, especially in the hips and spine
Cardiomyopathy (deterioration of the heart muscle) can occur later on in the disease progression
Some individuals display signs of cognitive impairments or learning disabilities
Elevated creatine kinase levels
Sources
Cropper, C. (2017, October 20). Risk factors for duchenne muscular dystrophy identified. Retrieved February 11, 2021, from
https://www.utsouthwestern.edu/newsroom/articles/year-2017/duchenne-muscular-dystrophy-risk-factors.html/
Johns Hopkins Medicine. (2021, January). Duchenne muscular dystrophy. Retrieved March 1, 2021, from
https://www.hopkinsmedicine.org/health/conditions-and-diseases/duchenne-muscular-dystrophy
Muscular Dystrophy Association. (2019, October 02). Diseases - dmd - diagnosis. Retrieved March 7, 2021, from
https://www.mda.org/disease/duchenne-muscular-dystrophy/diagnosis
Muscular Dystrophy Association. (2021, February 08). Diseases - dmd - medical management. Retrieved March 9, 2021, from
https://www.mda.org/disease/duchenne-muscular-dystrophy/medical-management
National Institute of Health. (2020, September 11). What are the treatments for muscular DYSTROPHY (MD)? Retrieved March 7, 2021, from
https://www.nichd.nih.gov/health/topics/musculardys/conditioninfo/treatment
NCH Healthcare System. (2020, January 31). Muscular dystrophy. Retrieved February 15, 2021, from
https://www.nchmd.org/education/mayo-health-library/details/CON-20375371
Nowak, K., & Davies, K. (2004, September 5). Duchenne muscular dystrophy and dystrophin: Pathogenesis and opportunities for treatment. Retrieved February 5, 2021, from
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1299132/
Patient Project Muscular Dystrophy. (2018, April 23). What is Duchenne? Retrieved March 31, 2021, from
https://www.parentprojectmd.org/about-duchenne/what-is-duchenne/progression/
CDC. (2020, October 27). MD STARnet data and statistics. Retrieved February 16, 2021, from
https://www.cdc.gov/ncbddd/musculardystrophy/data.html
Acsadi, G., MD. (2021, March 25). Duchenne muscular dystrophy. Retrieved February 5, 2021, from
https://rarediseases.org/rare-diseases/duchenne-muscular-dystrophy/
Romitti, P., Zhu, Y., & Puzhankara, S. (2015). Romitti et al. prevalence Of DUCHENNE and becker Muscular Dystrophies in the United States. pediatrics. 2015;135(3):513-521. PEDIATRICS, 135(5), 945-945. doi:10.1542/peds.2015-0652
Stanford Healthcare. (2017, September 11). Symptoms of Duchenne Muscular Dystrophy. Retrieved March 2, 2021, from
https://stanfordhealthcare.org/medical-conditions/brain-and-nerves/duchenne-muscular-dystrophy/symptoms.html
U.S. Department of Health and Human Services. (2020, September 3). Becker muscular dystrophy. Retrieved March 28, 2021, from
https://rarediseases.info.nih.gov/diseases/5900/becker-muscular-dystrophy
Treatments
Braces
Help support the foot and ankle
If one suffers from cardiomyopathy the following medications have proven to be helpful in slowing deterioration
angiotensin converting enzyme (ACE) inhibitors
angiotensin receptor blockers (ARB)
beta blockers
Corticosteroids
Glucocorticoids to increase muscle strength and slow the progression of the disease
Prednisone
Deflazacort
Help slow the progression of muscle weakness
Drugs for exon skipping
Exondys 51 (eteplirsen) injection used in patients with the mutation of the dystrophin gene amenable to exon 51 skipping
Vyondys 53 (golodirsen) and Viltepso (viltolarsen) used in patients with mutation of the dystrophin gene with exon 53 skipping
Orthopedic surgery may be required to fix extreme contractures, scoliosis, and muscle deformities
Physical and occupational rehabilitation to improve muscle strength
Respiratory therapy can be done to improve strength in diaphragm, expiratory, inspiratory, and accessory breathing muscles
Diagnostics
Molecular genetic tests can be done to identify specific a genetic mutation that leads to DMD
About 70-80% of DMD cases present with a large gene deletion or duplication
Some patients present with a very small mutation like a frameshift, deletion, or duplication
Blood tests that indicate a frequent surplus of creatine kinase in the blood
A muscle biopsy
Utilize techniques like: immunostaining, immunofluorescence or immunoblot to see antibody reactions against dystrophin
Alterations in muscle tissue that indicate towards DMD can be viewed under a microscope
The amount of dystrophin found on a biopsy helps narrow down whether or not eh patient has DMD or BMD
If one's dystrophin quantity is below 5% of the normal value, it's indicative of DMD
Electromyograms are performed to determine the source of the muscle weakness by using electrical impulses to contract and relax the muscle
Electrocardiograms may be performed to monitor heart rhythm to determine heart muscle strength or deterioration
Lung monitoring tests to evaluate strength of breathing muscles may be done to view progression of the disease
Incidence & Prevalence
Affects roughly 250,000 Americans
Onset of DMD is most common between 3-5 years of age
Impacts 1/3,500 males and occurs in 1/10,000 sex gametes like the eggs or sperm
Women pass down the DMD gene because men give their Y chromosome, not their X
For a girl to have DMD she would have to have both X chromosomes have the gene mutations for DMD
DMD is 3x more common than BMD
Becker's Muscular Dystrophy is a mutation in the DMD gene, where dystrophin is still present but in reduced quantities
The symptoms for BMD occur later and progress at slower rates than those of DMD
More prevalent in males because it's an X-linked recessive disease
Women have a 1/4 chance with each pregnancy to give birth to a daughter who carries the gene for DMD, a 1/4 chance for a normal daughter that isn't a carrier, a 1/4 possibility of giving birth to a boy with DMD, and a 1/4 possibility to have a normal son who isn't a carrier
Combined, Duchenne's Muscular Dystrophy and Becker Muscular Dystrophy impacts around 1/7,250 males from 5-24 years of age
More prevalent among Hispanic and White populations than African Americans
Risk Factors
Being a male increases the chances of having DMD due to only having 1 X chromosome
People who have a family history of DMD are more likely to possess the trait for it
Those with lower BMIs are more likely to be more heavily impacted by DMD
Those with weaker lung elasticity and function have an increased risk of dying from DMD
Evidence of a mutation at the Xp21.2 locus on the X chromosome
If a young child (specifically toddlers) constantly walk on their toes it can be an indication of early onset DMD
Being Caucasian doubles to triples the risk that a boy will be born with DMD
Increased protein levels in the blood and urine
Females with DMD are at highest risk for developing cardiomyopathy