B6.020 Prework 2: Muscular Dystrophies Flashcards
signs of M.D. in a newborn
floppy infant often preterm poor head control poor feeding prolonged labor maternal complications
signs of M.D. in child development
delay in milestones
signs of M.D. in teens/adults
difficulty in self care, swallowing, athletic/endurance activity
things to check on ROS for MD
school functioning/cognitive development
cardiac function/ arrhythmias/ syncope
respiratory
things to check on physical exam when suspicious of MD
signs of wasting or hypertrophy/ pseudohypertrophy muscle strength hyper vs hypotonia in weak areas deep tendon reflexes normal sensation joint contracture
what is MD
group of genetic disorders that are characterized by progressive loss of muscle integrity, wasting, and weakness
characterized by degeneration and regeneration of muscle fibers (in contrast with static or structural myopathies)
populations with higher prevalence of MD
French Canadians in Quebec
Israeli Bukharan Jews
signs of Duchenne and Becker MD
- normal milestones until walking begins
- toe walking, waddling gait, difficulty climbing stairs
- progressive difficulty rising from floor or chair
- Gowers sign @ 3
- Trendelenburg gait @ 6
- pseudohypertrophy of calf muscles
- contractures of heel cords
- kyphosis and scoliosis during childhood
- decline in lung function (adolescence)
- progressive cardiomyopathy (Becker)
- intellectual impairment in 25%
forms of myotonic dystrophy (DM)
DM1 and DM2
-different genes both AD inheritance
DM1 more common
combined prevalence: 1/8000
underlying common molecular pathogenesis despite different genes
extreme variability in penetrance of specific symptoms exist in the patient population
hallmark features of DM
myotonia
cataracts
cardiac conduction defects
major differences between DM1 and DM2 presentation
- more ptosis in DM1
- distal and facial involvement absent in DM2 (proximal involvement sooner)
types of DM1
- mild (50 to 150 repeats)
- classic (150 to 1000 repeats)
- congenital (>1000 repeats)
appears of patient with severe DM1
tent shaped mouth facial diplegia indistinct or nasal speech dull expression frontal balding with temporal wasting ptosis
diagnostic challenge of DM1
wide spectrum of manifestations
many not clearly related to skeletal muscle
MSK symptoms of DM1
muscle weakness: distal limb, facial, axial
distal distribution is exception to general rule of other myopathies having proximal involvement and neuropathies typically having distal
rare to lose ambulation (splints or bracing)
myotonia
what is myotonia
slow relaxation of muscle after contraction
usually detectable at age 5
severity of myotonia does not parallel the degree of weakness
NOT painful
neurological symptoms of DM1
cognitive deficit varies from none to marked
-worse w congenital
cataracts
excessive daytime somnolence
endocrine symptoms of DM1
insulin resistance
gonadal atrophy
GI symptoms of DM1
smooth muscle involvement: slow gastric emptying, poor peristalsis, constipation
cholecystitis
CV symptoms of DM1
usually heart block in Purkinje conduction system and arrhythmias rather than cardiomyopathy
-ECG abnormalities in 37-80%
who is at risk of congenital DM
infants born to mothers with symptomatic DM
>1000 repeats in DMPK gene
symptoms of congenital DM
clubfoot and contractures generalized hypotonia and weakness at birth facial wasting require gavage feeding or vent support severe GI problems *emergent action required
mortality of congenital DM
16-41% in neonatal period
contributors to reduced survival: resp failure and elective withdrawal of care
demonstration of myotonia on physical exam
sharp percussion of muscle with a reflex hammer or after firm voluntary contraction elicits sustained involuntary contraction
fades slowly over a matter of seconds
describe the process of EMG
needle is inserted in a muscle
electrical activity is recorded while muscle is contracting and resting
denervated muscles have increased abnormal activity like fibrillation and there is decreased interference pattern with contraction
narrows Ddx by excluding primarily neuro processes
nerve conduction studies
peripheral nerve stimulated w shocks at several points along its course to a muscle
time to initiation of contraction is recorded
determines conduction velocity (often slowed in neuropathy)
importance of CK in muscular dystrophy
D/BMD values in thousands
DM -normal or mild elevation
other lab abnormalities in MD
liver enzymes and LDH often elevated
histo features on biopsy
genetics of D/BMD
deletions of DMD gene clusters around 2 hot spot regions
-multiplex PCR amplifies these regions, detects > 98% of deletions
genetics of DM
PCR of repeat region to determine presence/extent of expansion
