Muscular dystrophy & cerebral palsy Flashcards
Muscular Dystrophy (MD)
- Inherited myopathic disorders characterized by progressive weakness
and wasting
Different types of Muscular dystrophy
– Duchenne
– Becker
– Limb-Girdle
– Facioscapulo-humeral
– Emery-Dreifuss
– Distal
– Ocular
– Oculopharyngeal
– Myotonic dystrophy
Duchenne Dystrophy epidemiology
– Rare muscle disorder, one of the most frequent genetic conditions
affecting approximately 1 in 3,500 male births worldwide.
– Average Age of diagnosis: 5 years old (3-6yo)
* About 2.5 years from initial symptoms to diagnosis
– More than 30 forms of MD, Duchenne is the most common
– >90% of people with the disease are in wheelchairs by age 15
The Role of Dystrophin in duchenne dystrophy
– Protein coded by DNA→RNA→Protein
– Anchor complex of other proteins responsible for communication with the extracellular matrix (eg. Ca++)
– Malformation or absence can cause gaps in cell membrane
– Decreased function of muscle cells and lead to death of cells
Duchenne Dystrophy clinical presentation
– Proximal muscle weakness
– Thin, weak thighs
– Weak gluteal muscles
– Pseudohypertophy “fat calves”
– Tip toe walking
– Poor balance
– Shoulders and arms held back
– Gower’s sign (walk up body to stand)
– 1/3 of pts have cardiomyopathy by
14 yo, virtually all pts by 18 yo
– Wheelchair dependent by 10-12 yo
Duchenne Dystrophy diagnosis
– Clinical presentation leading to suspicion
– Muscle biopsy with immunostaining analysis of dystrophin
– DNA analysis for mutations on X chromosome
– Can also get a CK if suspicious, can be 100 x normal limit
Duchenne Dystrophy treatment
– Supportive care
* PT for active and passive exercise, OT, Speech Therapy, Respiratory
Therapy
* Bracing limbs
– Medication
* Prednisone or deflazacort (corticosteroids)
– Surgery
* Mostly for scoliosis causing internal organ issues
Becker Dystrophy
- Becker is very similar to Duchenne except…
– Dystrophin gene is functioning, but abnormally.
– Malformed Dystrophin is produced in low concentration
– Think of a slow progressing Duchenne MD
Becker Dystrophy presentation
– Same as Duchenne, but slower progression and slower onset.
– Pts may have normal lifespan
Becker Dystrophy treatment
– Supportive care
– Medication
* Prednisone or deflazacort (corticosteroids)
– Surgery
* Mostly for scoliosis causing internal organ issues
Myotonia = ____
Sustained contraction
Myotonic Dystrophy types 1 and 2
Type 1: DMPK gene on chromosome 19
– Normal DMPK Expression = Myotonic Dystrophy Protein Kinase(DMPK)
* In muscle, DMPK turns off myosin phosphatase
and allows relaxation of muscle contraction
Type 2: CNBP gene on chromosome 3
– Normal CNBP Expression = Cellular Nucleic Acid Binding Protein (CNBP)
* Found in muscle and heart tissue, exact function is unclear, but thought to be a regulatory protein for other proteins
Myotonic Dystrophy “anticipation”
- A parent who already has a CTG or CCTG expansion will pass an already expanded CTG or CCTG sequence to offspring
- As the offsprings cells replicate the expansion is greater and symptoms appear sooner than parents.
- If the offspring passes their expansions along to the next generation,
then the expansion becomes greater and symptoms appear earlier and so does severity. - The process continues and families start to see earlier onset and severity so they start to “anticipate” the onset in following generations
Myotonic Dystrophy: type 1 presentation
– Congenital form is seen at birth with hypotonia
and inability to breathe or feed, not a good survival
rate
– Adult form: weakness develops later in life
* Mostly seen in facial features and distal limbs
– Ptosis, hollow cheeks, prominent forehead
– Hand muscle weakness
– lower leg, toe, or foot drop
* Sustained contraction of:
– handshake
– calf muscles
– toes
Myotonic Dystrophy: Type 2 presentation
– Only seen in Adults
* More mild than Type 1
* Proximal muscles affected (type 1 was more distal muscles)
– Hips and thighs
– Shoulders and upper arms
* Weakness and delayed relaxation of muscles in areas listed
– Trouble climbing stairs
– Difficulty standing
– Difficulty lifting
Myotonic Dystrophy diagnosis
– Clinical Presentation
* Age of onset between 20-40 ish
* Family history
– Lab testing - DNA testing to confirm CTG or CCTG repeats
Myotonic Dystrophy treatment
– Mexiletine first-line for those pts limited by myotonia (no treatment for
weakness)
* Can potentiate cardiac arrhythmias
– Do not use in pts with 2 nd or 3 rd degree AV block or with
abnormal EKG
– Other meds: Procainamide, phenytoin, quinidine, carbamazepine
– Bracing of effected weak limbs, wheelchairs
– PT, OT, other adjunctive therapies and specialists (eg. Cardiology)
Cerebral Palsy =
brain disease causing paralysis
* Cerebral Palsy is an umbrella term for a group of non progressive movement disorders affecting how a person moves.
* Syndrome, not a specific disorder
Cerebral Palsy etiology
– Prematurity, Low birth wt - Physical stress and demands on the immature brain is thought to put this population at higher risk
– In utero disorders
– Neonatal encephalopathy
– Kernicterus (bilirubin encephalopathy)
– Perinatal asphyxia, stroke, CNS infections account for 15-20% of
cases
– Multiparity
Cerebral Palsy - Pathophysiology
– Injury or abnormal development of the prenatal and neonatal brain can occur at any
time
* depending on stage of development, varied demonstrations of CP can be manifested
* Usually damage from genetic abnormalities, toxic or infectious etiology, or vascular
insufficiency
* Prematurity - physical stress and demands on the immature brain is the main
thought as to why immature infants are at higher risk
Location of damage to the brain can dictate what symptoms are demonstrated with cerebral palsy
- Cerebellum – Coordination of movements
- Motor Cortex – Initiation of movements
- Basal Ganglia –Initiation and prevention of movements
Cerebral Palsy - etiology
– Hypoxic-ischemic injury
– Structural malformations
– Vascular disorders
– Intraventricular or subarachnoid
hemorrhage
– Intrauterine infections
– Toxins
– Trauma
– Metabolic disorders
– Prematurity (low birth wt)
– Hemolytic diseases
– Maternal hyperthyroidism
– Maternal seizures
– Maternal infection
– Stroke
– Meningitis
– Sepsis
– Third trimester bleeding
– Incompetent cervix
– Maternal use of hormones
– Meconium in amniotic fluid
Cerebral Palsy Classifications
– Severity – Gross Motor Function Classification System (GMFCS)
– Body area – Monoplegia, Diplegia, Hemiplegia, Quadriplegia
– Type – Spastic, Dyskinetic, Ataxic, Mixed
Gross Motor Function Classification System (GMFCS) for cerebral palsy
– Level 1 - Walks without limitations
– Level 2 - Walks with limitations
– Level 3 - walks using a hand-held mobility device
– Level 4 - Self-mobility with limitations; may use powered mobility
– Level 5 - Transported in a manual wheelchair
