Duchenne & Becker muscular dystrophy – causes, symptoms, treatment & pathology

Duchenne & Becker muscular dystrophy – causes, symptoms, treatment & pathology

With muscular dystrophy, “dys” means bad
or difficult, and “troph” means nourish; so muscular dystrophy basically refers to
the muscle appearing poorly nourished because of degeneration, which leads to muscle weakness. Under a microscope, a biopsy of the tissue
shows changes in the muscle itself but not in the nerve or neuromuscular junction; this
distinguishes muscular dystrophy from other problems that cause muscle weakness as a result
of nerve damage, like neuropathies. Muscular dystrophy is actually a group of
disorders, all of which are caused by genetic mutations. Within that group, dystrophinopathies are
the most common, which includes Duchenne muscular dystrophy, or DMD, and Becker muscular dystrophy,
both of which result from mutations in the dystrophin gene. In addition to those two, genetic mutations
in other genes are responsible for several dozen other muscular dystrophies, some of
which code for proteins that form a protein complex with dystrophin protein. These other muscular dystrophies, therefore
end up causing a lot of the same symptoms as the dystrophinopathies. Now, the fact that both Duchenne and Becker
muscular dystrophy result from mutations in the same dystrophin gene means that they are
“allelic disorders,” and when a mutation occurs in dystrophin that’s severe enough
to result in no protein at all, for example a nonsense or a frameshift mutation, the result
is Duchenne muscular dystrophy, which ends up being the more severe of the two, with
symptoms usually presenting by age 5. On the other hand, mutations that allow for
a misshapen protein to form, like missense mutations, lead to Becker muscular dystrophy
which is basically a milder form of Duchenne muscular dystrophy that presents later on,
usually between age 10 to 20. Alright so the dystrophin gene is a huge gene
on the X-chromosome, that has 79 exons and is over 2 million base pairs in length. By comparison, most genes have only about
10 exons and are 50 thousand base pairs in length. More base pairs and more exons mean that there
are more chances for mistakes during meiosis, which is when the egg or sperm are being created. Most of these gene mutations are deletions
or duplications of one or more exons, and a small amount are point mutations. Now males males have one X and one Y chromosome,
and females have two X chromosomes. This means it’s way more common in boys,
because they only have one copy of the dystrophin gene, and if that copy’s defective, it’s
the only one available to muscle cells, whereas girls with a defective dystrophin gene might
have another functional one. Since this is linked to the X chromosome,
both Duchenne and Becker muscular dystrophy are called X-linked recessive. In females, though, only one X chromosome
gets expressed, and the other is inactivated, called X-inactivation or lyonization. Now if this inactivation’s random, you’d
expect about half of the female’s cells to have a functional dystrophin gene and the
other half to have a defective dystrophin gene, and these people are typically asymptomatic. Having said that, if more cells end up with
the defective dystrophin gene, and less with the functional one, they can end up being
“manifesting carriers,” meaning that they manifest or show some symptoms. Alright so the dystrophin protein links intracellular
actin with the “dystrophin-associated protein complex,” which is a cluster of cytoplasmic
and cell membrane proteins that are anchored to the extracellular matrix around the muscle
cell, making that link between cytoskeletal actin and the extracellular matrix stabilizes
the sarcolemma, or muscle cell membrane, in the same way that a large wooden support beam
running along the roof keeps a house sturdy. Without the support of dystrophin in place,
the sarcolemma essentially wilts and becomes unstable. Over time, cellular proteins like creatine
kinase, or CK, start escaping the damaged cell and calcium starts to enter the cell,
and this ultimately leads to cell death. In the short term, there is muscle regeneration
resulting in muscle fibers of different sizes, but in the long term, the muscles atrophy
and are infiltrated by fat and fibrotic tissue, which leaves them really weak. This process is particularly noticeable in
the legs, and children with Duchenne muscular dystrophy begin to walk later in childhood,
and they have they have a “waddling” gait, and they tend to develop calf pseudohypertrophy,
where they have visibly enlarged calves which are large because of fat and fibrotic tissue
rather than muscle tissue. Another classic sign of Duchenne muscular
dystrophy is Gowers’ sign, where if a child is lying down flat on their stomach, they
will slowly stand up with the help of their arms, because of weak muscles around the hips
and upper legs. Later symptoms include needing a wheelchair
because of severe weakness, developing respiratory failure because of a weak diaphragm, scoliosis,
and developing dilated cardiomyopathy and arrhythmias since the dystrophin protein is
also expressed in heart muscle. Unfortunately, these complications often lead
to a shortened lifespan. For diagnosis, people with Duchenne or Becker
muscular dystrophy often have a high creatine kinase level, and the diagnosis can be confirmed
by looking for mutations in dystrophin (by either DNA tests or Western blot), as well
as having a muscle biopsy with staining for dystrophin. Unfortunately, there are no great treatments
for Duchenne or Becker muscular dystrophy. Glucocorticoids can sometimes slow degeneration,
but can also result in side effects like excessive weight gain. Other treatments like physical therapy and
conditioning can improve quality of life, but they don’t reverse the underlying process. Given the possibility of genetic inheritance,
counseling parents of the person and understanding the risk of having another child with these
conditions is important. About 2/3 of the time the person’s mother
is a carrier and the the other 1/3 of the time the disease is sporadic, which means
it’s caused by a new mutation. If the mother is a carrier, and we look at
her future sons, half or 50% will end up having the mutation, and if we look at her future
daughters, half or 50% of them will be carriers for the mutation. Okay so as a quick recap: the protein dystrophin
is super important for stabilizing the muscle cell membrane. Mutations in the dystrophin gene that lead
to a loss of dystrophin leads to duchenne muscular dystrophy, whereas mutations in the
dystrophin gene that leads to misshapen dystrophin leads to Becker muscular dystrophy. Thanks for watching, you can help support
us by donating on patreon, or subscribing to our channel, or telling your friends about
us on social media.

100 Replies to “Duchenne & Becker muscular dystrophy – causes, symptoms, treatment & pathology”

  1. I am from Bangladesh. My younger brother is suffering from DMD. He is now 13 years old. Is there any treatment discover yet? Please inform me….

  2. 在下有點個人意見:雖然看上去肌肉像是不發達,但實際情況可能是:有些肌肉沒收到或沒反應神經系統所發的訊號,而無法收縮(像是過不到電)。修正方法是封閉這些特殊肌肉的微動脈,使他收不到養份,並帶走原先儲存在的養(可能要用微電/抽走/化學流失的方法)

  3. For all of you guys out there with functioning muscles… you are very, very, very lucky. I have DMD, and it is the worst thing you can think of. I wouldn't wish this on my worst enemy.

  4. Great video and very clearly explained. I wonder about the inheritance description though. If mum is a carrier you say, "50% will end up having the mutation". Not necessarily so. Instead, there is a 50% chance of inheritance with each new pregnancy.

  5. Just for some more info, I'm an interesting case. Diagnosed at 5 (DMD), symptoms at this age, but did well past wheelchair stage, diagnosed changed to (severe BMD), nonsense mutation determined, now 26, still fully mobile, driving with no mods, but still progressing. Waiting for Translarna to be approved in Canada.

  6. such a nice short video that states all points without beating around the bush 🙂 thank you so much this helped me understand it easily

  7. I have BMD
    I'm 47 a male.
    I'm Still walking but with a cane and walk very slow
    I'm still driving a car too
    I was diagnosis with Becker's muscular dystrophy at age 29
    I'll be honest I'm having a real hard time mentally dealing with muscular dystrophy at 47
    I like to stay busy doing stuff but I can't bend down pick stuff up that I drop alot because my right arm has gotten very weak in the 2 years

  8. My brother passed away from this disease this year a week before his birthday back in March of 2018

  9. Thanks for helping at end moments…. m abt 2 write exms …. thanks for awesome explanation…😊

  10. The enlarged calf muscles with BMD are maybe one of the biggest hinderences as the quad muscle has to work even harder as there is definetly alot more more weight due to the fatty tissue if only there was a way of gaining lean muscle in the calf or even reducing the fatty tissue it may help quality of life. Personally ive tried quite a few supplements like aloe vera and creatine but little results now im trying testosterone booster few weeks in there could be some extra strength overall and with your core, i will report back if anything more dramatic. I know they have done testosterone therapy for DMD and there have been benefits but that is pure form of testosterone perscripted by a doctor unsure if it would help BMD also.

    Stay strong folks there has been breakthroughs so hopefully in the not to distance future we could have something. Im 32 btw with BMD and im doing fairly well still able to walk good distances and get up stairs slowly and at times disguise my condition altogether.

  11. There is a new drug they just started testing in the US this year, but it is already approved in Germany and in the UK. We enrolled our little son (7 yo) only 3 months ago (in may) and are seeing some progress in walking. Moreover, it is free because it is a part of an FDA study. I'm just sending messages to folks in the community spreading the news. Find me on facebook Jessica Titoff

  12. My cousin is suffering from duchenne muscular dystrophy…
    Is there any treatment
    Can a person get recovery out of this 😭
    I'd someone can help so please mention

  13. I think I got the speratic mutation for beckers becuase none of my late family has it. But at the same time my brother has it and it affects him differently than me. While I have the worst of it my brother has less of an effect. Apparently its rare, like 1% rare to have two brothers with different mutations of the same genetic disease.

  14. the pain of beckers is ungodly. It feels like something is eating you on the inside of the muscle and believe me when I say I would give this to my worst enemy.

  15. I am a 4th-year medical student and today I made a friend in the hospital with Becker muscular dystrophy. He is 40 years old and has been living in the hospital for many years because of the complications and need for monitoring. Anyway, I just wanted to say that he has literally the best personality, polite, and funny. I really admire him for educating himself and becoming the person he is now, also his the kind of person that you would never get bored while talking to him. Words wouldn't be enough to describe him. God bless him. Just wanted to say have some faith, it is the beginning of a long journey be strong.

  16. shout out to my dad who has MD. he's the strongest man i know and i love him with all mt heart, and am so happy that he is still here, although walking is hard for him. <3

  17. Hi, I'm tushar, i'm 17, i'm from Guwahati, Assam, India.. i hve DMD, i can't walk since 2013 when i broke my right ankle.. i tried to walk, but it was difficult and painful.. i'm in wheelchair, can't go to school, i read books at home, i play video games on Playstation 3 for time pass, i'm really bored.. i hope there's cure comes out fast.

  18. I am an Italian girl who likes foreign languages, especially English, I am studying hygiene and anatomy in this last period of school because I would like to be part of the nursing environment. From this video I managed to understand everything, despite myself both Italian. My compliments. A nice clear video and well-made patterns and designs.

  19. Lost my little brother because of DMD.. back then there was'nt any cure for this.. i hope everyone that has it have a long life because now they finally have a way to cure this.

  20. My mother died at progressive muscular dystrophy
    She didn’t survive at that sick I’m 10 old today I’m going to a brave boy
    When my mother is not in our home she was a greatness mother in my life
    Then the doctor said “there’s weather a heart and lungs is going to be low”
    Then I woke up to my bed and called my grandma we crying then I saw her she is ded
    Then I saw my grandpa bring her to funeral parlor then I saw my mom she peed in her bed

    I sent this to everyone family, my step sister, and my father
    Pls don’t hate me I’m just trying to say this comment to my mother died

    I’m 10 old i born
    2008 December 10

    God bless to y’all to read this comment

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