DMD Flashcards
all movement is controlled by?
skeletal muscle
muscle are made of?
myocyte
which protein are located near the membrane myocytes?
dystrophin
what is the location of dystrophin?
dystrophin act like a chain that links the skeleton of the myocytes , made of actin , to the extra cellular matrix, which is mesh like structure outside the myocytes
This linkage prevent muscle damage when the muscle contract
or
Dystrophin is a protein located between the sarcolemma and the outermost layer of myofilaments in the muscle fiber (myofiber). It is a cohesive protein, linking actin filaments to other support proteins that reside on the inside surface of each muscle fiber’s plasma membrane (sarcolemma).
what are the three important areas in dystrophin?
actin binding end (which attach to cellular skeletons)
central rod
dystroglycan- binding end which attaches to the dystroglycan complex within the memebrane that us attached to the extra cellular matrix
fuction of dystrophin?
this linkage prevent muscle damage when the muscle contract & relax
What are three roles of calcium in the body?
Calcium is the most abundant mineral in the body and has four primary functions: making bones strong and healthy, facilitating nerve-to-nerve communication, stimulating muscle contraction, and activating blood-clotting factors.
pathophysiology
in dmd genetic mutation
/causes dystrophin to be extremely short
/
often lacking the dystroglycan binding end(making it dysfunctional)
/
becoz of this every time muscle contract small rip appear in the membrane
/
these small rip allow diffusion of various molecules into & out of the myocytes
/
the most important substance involved in damaging muscle is calcium
/
calcium ions found plentifully outside of mayocyte
/
flow in through these small rips
/
active calcium dependent cellular enzymes that break down protein called protease
/
normally by carefully regulating cellular calcium levels, these protease only break down old & damage protein
/
however in dmd
/extremely high calcium levels activate too many of these protease which begin to break down important, functional protein as well
/
this kill the myocytes
/
another important molecule that diffuse through the rips is creatine kinase
/
which leak out of the cell
& eventually into the bood
/
this elevated level of creatine kinase is blood is often used to diagnose DMD
/
creatine kinase is an enzyme that stores energy for myocytes to use during contraction
/
which less creatine kinase, less energy storage occurs which also weakned muscle
/
muscle repair & degenerate at younger age but. as the person get older, muscle no longer regenerate fast enough to keep up with the constant death of myocytes
/
instead fat & scar tissue begin to fill in the gaps
/
since the fat & scar tissue are unable to contract muscle get weaker over time
/
this weaking lead to a distinct pattern of symptoms such as gower sign where the child use his or her arm to stand up because the leg muscle are too weak
what is muscular dystrophy?
Muscular dystrophy is a group of inherited diseases that damage and weaken your muscles over time.(progressive)
This damage and weakness is due to the lack of a protein called dystrophin, which is necessary for normal muscle function.
causes
caused by mutations in the dystrophin gene on x chromosome
age population
male > female
Clinical Presentation
The muscle weakness is mainly in the ‘proximal’ muscles, which are those near the trunk of the body, around the hips and the shoulders. Weakness typically starts proximally in the lower extremities, then moves distally. Weakness in the upper extremities tends to appear later[1]. This means that fine movements, such as those using the hands and fingers, are less affected than movements like walking.
The symptoms usually start around age 1-3 years, and may include:
Difficulty with walking, running, jumping and climbing stairs. Walking may look different with a ‘waddling’ type of walk. The boy may be late in starting to walk (although many children without DMD also walk late).
When you pick the child up, you may feel as if he ‘slips through your hands’, due to the looseness of the muscles around the shoulder.
Toe-walking, In this gait pattern, children walk on their toes with feet apart to help maintain balance, with an increased curve in the lower back[10].
Frequent falls
The calf muscles may look bulky, although they are not strong.
As he gets older, the child may use his hands to help him get up, looking as if he is ‘climbing up his legs’. This is called ‘Gower’s sign’.
Some boys with DMD also have a learning difficulty. Usually, this is not severe.
Sometimes, a delay in development may be the first sign of DMD. The child’s speech development may also be delayed. Therefore, a boy whose development is delayed may be offered a screening test for DMD. However, DMD is only one of the possible causes of developmental delay - there are many other causes not related to DMD.
Contractures are a classic finding in DMD[11]. It develops when tissues, such as muscle fibers, which are normally stretchy are replaced by hardened, non-stretchy tissue[11]. They are seen as a major cause of disability[12]. They prevent normal movement, and, for children with DMD, occur often in the legs, especially the calf and muscles around the hip
Progressive enlargement of heart
respiratory insufficiency
- diaphragm spared
- due to total inactivity (respiratory infection)
superficial reflex lost
eventually deep tendon reflex are lost
functional indepedency
intelligence
iq- 75 to 80 percent
git abnormalities
constipation
obesity
emotional disturbance
Physiotherapy Management
home program
- exe
- orthotic training
deformity
- stretching
- walking
- splint
spinal deformity
- wheel chair
- spinal orthoses
active exercises
- avoid overuse
- no resistance
- no eccentric
strengthening
- isokinetic submaximal
- mild moderate
- grip
- swim & cycling
ambulation prolonged
Afo orthoses
weight control
diet
steroid use
facilitating sleep
positing
repsiratory care
family support
pain
preparation of adult life
d/f between dmd & bmd
Dmd
dystrophin gene absent or non functional
incidence 1/3600 male births
mean age at onset 3-5 years
disease progression fast
mean age at becoming non ambulatory 12 years
mean life expectancy mid 20s
onset of cardiomyopathy usually follows skeletal progression
intelligence subnormal
associated problem cardiomyopathy
Bmd
dystrophin gene partially functional incidence 3/6/1 lakh male births mean age at onset 12 years disease progression slow mean age at becoming non ambulatory 27 years
mean life expectancy mid 40s
onset of cardiomyopathy may present before skeletal symptoms
intelligence normal
associated problem color blindness
Why do boys get more DMD than girls?
Duchenne MD affects boys more often than girls because the dystrophin gene is on the X chromosome. Boys have only one X chromosome and girls have two. So girls can almost always make working dystrophin using the dystrophin gene on their second X chromosome.
