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99 Cards in this Set
- Front
- Back
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DM1 genetics |
mutation in DMPK gene on chromosome 19 results in CTG trinucleotide repeat with anticipation
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DM2 genetics |
mutation in ZNF9 gene (zinc finger protein 9) in chr 3 results in CCTG repeat, no anticipation
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myotonic dystrophy 1 neurologic presentation |
can be congenital, childhood or adult onset
temporalis and sternocleidomastoid atrophy (hatchet face) grip and percussion myotonia with warm-up phenomenon distal weakness, foot drops weakness of facial muscles --> ptosis and facial droop frontal balding |
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treatment for severe myotonia
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mexiletine 150 tid
dilantin |
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systemic manifestations of DM1
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cataracts
gynecomastia sleep apnea with excessive daytime sleepiness and fatigue cardiac conduction defects diabetes male hypogonadism |
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myotonic dystrophy 2 presentation
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proximal weakness instead of distal weakness in DM1
muscle cramps and pains less severe neurologic and systemic disease |
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neuromuscular disorders that present with myotonia
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myotonic dystrophies
myotonia congenita --> autosomal dominant myotonia and recessive generalized myotonia neuromyotonia syndromes |
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myotonia congenita etiology and pathophysiology
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loss of function mutations of CLCN1 gene which encodes CIC-1 chloride channel essential for muscle
chromosome 7 decreased muscle channels on muscle membrane --> hyper-excitability and sustained contraction |
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myotonia congenita presentation
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prologued muscle contractions --> dysphagia, recurrent falls
warm-up effect --> muscle loosens with repetition autosomal dominant myotonia --> Thomsen's --> since birth, milder, hands/face/eyelids recessive generalized myotonia --> Becker's --> age 4-12, hypertrophy with weakness legs > face, severe |
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neuromyotonia syndrome presentation
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generalized stiffness
delayed relaxation hyperhidrosis direct percussion does not elicit myotonia continues during sleep or general anesthesia |
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dermatomyositis presentation
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proximal muscle weakness and muscle pain
heliotrope rash over eyelids, cheeks and/or chest Gottron's papules over MCP and PIP joints, elbows, knees associated with cancers --> breast, lung, ovarian, gastric |
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dermatomyositis work-up
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sometimes elevated CPK
elevated ESR, CRP EMG --> small polyphasic units with increased insertional activity, positive waves and fibs anti-Jo-1 antibodies, anti-SRP, anti-Mi2 |
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dermatomyositis antibodies
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anti-Jo-1 antibodies, anti-SRP, anti-Mi2
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dermatomyositis associated conditions |
associated with paraneoplastic syndrome from breast, lung, ovarian or gastric cancers
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dermatomyositis biopsy |
perifascicular atrophy +- perivascular and perimysial inflammatory CD4 cells
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polymyositis presentation |
painless proximal muscle weakness +- viral prodrome of fever, malaise, anorexia
most common in women 40-60 |
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polymyositis work-up
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CPK elevated up 100-fold
EMG --> small brief polyphasic units with fibs and positive waves biopsy --> endomysial CD8 cells with invasion of muscle fibers |
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polymyositis biopsy
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endomysial CD8 cells with invasion of muscle fibers
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inclussion body myositis presentation |
distal weakness of finger flexor muscles
quadriceps weakness and atrophy male > female most common myopathy in patients > 50 |
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inclussion body myositis work-up
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EMG --> prominent spontaneous activity with early recruitment
biopsy --> rimmed vacuoles and inclussion bodies, endomysial inflammation, variation in fiber size with hypertrophy |
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inclussion-body myositis biopsy
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rimmed vacuoles and inclussion bodies
endomysial and perimysial inflammation variation in fiber size and shape |
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myofibers
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syncytial muscle cell contains myofilaments of actin and myosin
can be intrafusal or extrafusal |
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endomysium
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connective tissue that surrounds myofibers
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muscle fascicle |
bundle of myofibers surrounded by perimysium
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perimysium |
connective tissue that surrounds muscle fascicles
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epimysium |
connective tissue that surrounds a muscle with its hundreds of fascicles
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extrafusal fibers |
contraction across joints
type I and type II |
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type I myofibers
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high oxidative metabolism, low glycogen
extrafusal slow-twitch fatigue-resistant red/dark muscle pale in alkaline ATPase; dark in acid ATPase |
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type II myofibers
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extrafusal
fast-twitch rich in glycogen and myophosphorylase dark in alkaline ATPase; pale in acid ATPase |
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intrafusal fibers
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myofibers within muscle spindle or golgi tendon organ
contain sensory stretch and tension receptors |
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stretch reflex
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monosynaptic reflex
stretch of muscle spindle --> Ia afferents of dorsal root ganglion --> alpha motor neuron fires |
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golgi tendon reflex
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polysynaptic reflex
stretch of golgi organ --> Ib afferents of dorsal root --> inhibitory interneuron --> inhibits alpha motor neuron |
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muscle depolarization physiology
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Ach binds Ach receptor on outer muscle membrane -->
depolarization --> activation of voltage-gated Na and K channels --> influx of Na through T-tubules and depolarization of inner membrane --> activation of dihydropyridine receptors (L-type voltage-gated Ca channels) --> activation of calcium-release channels (ryanodine receptors) --> release of calcium into sarcoplasmic reticulum --> muscle contraction |
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classification of muscular dystrophies
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dystrophinopathies --> Duchene, Becker's
FSHD limb-girdle muscular dystrophies myotonic dystrophy emery-dreifuss |
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presentation of dystrophinopathies
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x-linked --> affects only males but subclinical disease in female carriers
proximal muscle weakness calf pseudohypertrophy cramps, aches, pains toe walking, Gower sign dilated cardiomyopathies hyperCKemia Duchenne onset --> 3-5 years, more severe Becker's onset --> teenager or adult, less severe |
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genetics of dystrophinopathies
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x-linked recessive
mutation of DMD (dystrophin) gene on Xp21 duchenne --> no dystrophyn at all becker's --> some dystrophin present, disease is milder and later onset |
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treatment of dystrophinopathies
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corticosteroids --> slow disease progression, prolong ambulation by 1-3 years
ACEi --> for dilated cardiomyopathy pulmonary hygine and noninvasive ventilation |
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complications of dystrophinopathies
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dilated cardiomyopathy and arrhythmias
kyphoscoliosis restrictive lung disease cognitive impairment joint contractures |
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dystrophinopathy EMG
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low amplitude small units with early recruitment
with or without membrane instabiity |
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dystrophinopathy biopsy
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fibrosis and fat infiltration in endomysium
marked variability in fiber size inflammatory infiltrates regenerating fibers |
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emery-dreifuss muscular dystrophy presentation
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childhood onset
prominent elbow, wrist, ankle and back contraction deformities humeroperoneal weakness cardiac conduction defects and cardiomyopathies |
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emery-dreifuss muscular dystrophy complications
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cardiac conduction defects, heart blocks, arrhythmias, sudden cardiac death
require AICDs early |
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emery-dreifuss muscular dystrophy genetics
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variable genetics and phenotypes but classic emery-dreifuss is x-linked recessive
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FSHD presentation |
usually onset before age 20
bilateral scapular winging triple bulge sign --> deltoid, bone and trapezius bumps when arms are raised weakness of facial and scapular muscles, biceps, triceps, pectoralis, serratus anterior usually asymetric |
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FSHD genetics
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autosomal dominant decrease in D4Z4 repeats in chr 4
up to 30% of cases are sporadic |
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FSHD complications
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neck and back pain due to paraspinal muscle weakness
kyphosis hearing loss in 75% retinal vascular abnormalities LE weakness in peroneal muscles, 20% may eventually require wheelchair |
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FSHD EMG
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low amplitude small units with early recruitment
with or without membrane instabiity |
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most important glycogen storage diseases
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Pompe's (GSD II) --> alpha-glucosidase deficiency or acid maltase
Cori (GSD III) --> debranching enzyme deficiency Andersen (GSD IV) --> McArdle (GSD V) --> myophosphorylase deficiency |
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glycogen storage disease type II pathophysiology
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acid maltase deficiency/ lysosomal alpha glucosidase deficiency leads to accumulation of glycogen
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glycogen storage disease type II phenotypes |
severe infantile form (Pompe's disease)
juvenile onset adult onset |
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Pompe's disease presentation
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glycogen storage disease type II severe infantile phenotype
hypotonia, macroglosia, hepatomegaly cardiac symptoms and failure to thrive respiratory failure and death by two years |
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glycogen storage disease type II juvenile form
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delayed motor milestones and development with limb-girdle pattern of proximal weakness
calf hypertrophy, Gower's sign, waddling gait no hepatomegaly or cardiomegaly |
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glycogen storage disease type II adult onset form
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proximal or distal weakness and respiratory muscle weakness
no hepatomegaly or cardiomegaly |
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glycogen storage disease type II laboratory work-up
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best screening test --> dried blood spot test for alpha-glucosidase activity followed by genetic testing if abnormal
forearm test pyruvate, ammonia and lactate all normal moderate elevation of CK |
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glycogen storage disease type II EMG
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normal NCVs
EMG shows fibs, positive sharp waves, CRDs and sometimes myotonic discharges in paraspinal muscles myopathic units with early recreuitment |
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glycogen storage disease type II muscle biopsy
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prominent non-rimmed vacuoles appearance
PAS stain shows increased glycogen deposits acid-phosphatase positive lysosomes (glycogen gets stored in lysosomes) |
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Pompe's disease treatment
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enzyme replacement therapy with alglucosidase alpha
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Cori disease pathophysiology |
deficiency of debranching enzyme leads to accumulation of glycogen in the cell but not lysosome
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Cori disease presentation |
different phenotypes and age of onset
recurrent fasting hypoglycemia seizures hepatomegaly hypotonia growth retardation |
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Cori disease forearm exercise test
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normal increase in ammonia with no rise in lactate
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Cori disease biopsy |
prominent non-rimmed vacuoles appearance
PAS stain shows increased glycogen deposits acid-phosphatase negative lysosomes (glycogen does not get stored in lysosomes) |
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Andersen disease pathophysiology
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branching enzyme deficiency
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Andersen disease presentation |
different phenotypes and age of onset
may include hepatosplenomegaly, liver cirrhosis, myopathy and cardiomyopathy |
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Andersen disease muscle biopsy
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PAS-positive, diastase-resistant polyglucosa bodies (filamentous polysacchrides)
no glycogen deposits because there is no branching enzyme |
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McArdle disease pathophysiology
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myophosphorylase enzyme deficiency involved in conversion of glycogen to glucose in muscle
only affects skeletal muscle |
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McArdle disease presentation
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onset in childhood of exercise intolerance, fatigue, myalgias, cramps, poor endurance, weakness
symptoms appear after short-term intense activity or prolongued low-intensity excersise second-wind phenomenon is present |
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McArdle disease forearm exercise test
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normal ammonia with no rise in lactate
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McArdle disease muscle biopsy |
excessive subsarcolemal and intermyofibrillar glycogen deposits
staining for myophosphorylase is absent |
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calcium channelopathies
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familial hypokalemic periodic paralysis
secondary hypokalemic periodic paralysis |
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sodium channelopathies
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hyperkalemic periodic paralysis
paramyotonia congenita |
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mitochodrial myopathies
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mitochondrial epilepsy with ragged red fibers
MELAS --> mitochondrial myopathy, lactic acidosis and strokes |
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mitochondrial epilepsy with ragged red fibers
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X-linked
myoclonic and GTC seizures ataxia dementia sensorineural hearing loss optic atrophy proximal muscle weakness and exercise intolerance |
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MELAS
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mitochondrial myopathy lactid acidosis and strokes
proximal weakness and exercise intolerance recurrent migraines, hemiparesis, hemianopsia and cortical blindness plus/minus dementia and seizures |
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myelin associated proteins
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MPZ (myelin protein zero) --> PNS
myelin-associated glycoprotein --> CNS and PNS PMP22 (peripheral myelin protein 22) --> PNS MOG (myelin-olygodendrocyte glycoprotein) --> CNS OMgp (oligodendrocyte-myelin glycoprotein) --> CNS |
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X-linked myopathies
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dystrophinopathies (DMD and BMD)
myotonic dystrophy Emery-Dreifuss |
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general presentation of LGMDs
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genetic with postnatal onset
progressive weakness and atrophy of proximal muscles |
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generalities about autosomal dominant Vs. recessive LGMDs
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autosomal dominant LGMDs account for about 10-15% and have lower levels of CK
the majority of LGMDs are autosomal recessive and have high CK levels |
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most common types of LGMDs
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calpainopathies ~30%
sarcoglycanopathies 15-20% FKRP 15-20% dysferlinopathies 15-20% all autosomal recessive |
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forearm exercise test
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blood drawn for pyruvate, ammonia, lactate
patient performs open/closeure of hand and labs are drawn at 1, 2, 4, 6 and minutes post exercise normal response is 3-5-fold increase in pyruvate, ammonia and lactate |
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steroid-induced myopathy
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normal CK
EMG shows nonspecific myopathic changes pathology shows atrophy of type II fibers |
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centronuclear myopathy presentation
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ptosis
ocular palsies facial, pharyngeal and laryngeal muscle weakness hypotonia at birth hyporeflexia repiratory failure if severe |
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centronuclear myopathy labs, EMG and biopsy
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labs --> mildly elevated CK
EMG --> small units, early recruitment, positive waves and fibs pathology --> small and hypotrophic muscle fibers, predominantly type I and central nucleation |
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congenital muscular dystrophy general presentation
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all autosomal recessive
maniests at birth or within 2 years of life congenital hypotonia delayed motor milestones progressive disease mild-severe cognitive impairment and learning disabilities +/- seizures |
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most common congenital muscular dystrophies
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dystroglycanopathy muscular dystrophies (Fukuyama, muscle-eye-brain, WWS)
collagen type VI disroders (Ulrich, Bethlem) merosin-deficient congenital muscle dystrophy (laminin-alpha 2 deficiency) Fukuyama congenital muscle dystrophy (Japan) |
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dystroglycanopathies
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Fukuyama congenital muscle dystrophy
muscle-eye-brain disease Walker-Warburg syndrome |
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dystroglycanopathies presentation
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severity --> Fukuyama < muscle-eye-brain < Walker-Warburg
congenital muscular dystrophy at birth (floppy baby) severe MR seizures eye abnormalities --> myopia, cataracts, abnormal eye movements, pale discs, retinal detachment. no blindness. brain structural malformations --> polymicrogyria, pachygyria, agyria and others |
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congenital muscular dystrophy with merosin deficiency
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AKA laminin-alpha 2 deficiency
autosomal recessive mutations of LAMA2 gene congenital muscular dystrophy symptoms correlate with amount of deficiency seizures normal cognition no eye abnormalities cardiac abnormalities in 25% deep and subcortical white matter changes mostly periventricular and frontal U fibers |
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collagen VI-deficient congenital muscular dystrophies
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Ulrich congenital muscular dystrophy
Bethlem myopathy |
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collagen VI-deficient congenital muscular dystrophy presentation
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congenital hypotonia
proximal joint contrctures distal joint laxity folicular keratosis and abnormal keloid formation normal cognitive function and MRI imaging |
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congenital muscular dystrophy differential --> cognitive impairment and eye abnromalities
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dystroglycanopathy --> Fukuyama, muscle-eye-brain, Walker-Warburg
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congenital muscular dystrophy differential --> cardiac involvement |
congenital muscular dystrophy with merosin deficiency
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congenital muscular dystrophy differential --> distal joint laxity and keloid |
collagen VI-deficient congenital muscular dystrophy --> Ulrich, Bethlem
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congenital muscular dystrophy differential --> MRI abnormalities |
dystroglycanopathies --> Fukuyama, muscle-eye-brain, Walker-Warburg
congenital muscular dystrophy with merosin deficiency |
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congenital myopathy general presentation
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congenital hypotonia
delayed motor milestones facial muscle and respiratory involvement nonprogressive no cognitive involvement 90% normal CK in nemaline |
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most common congenital myopathies
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nemaline myopathy
central core disease centronuclear myopathy |
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oculopharyngeal muscular dystrophy
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autosomal dominant GCG repeat expansion in the poly-A-binding protein gene
pharyngeal muscle weakness --> dysphagia, dysphonia ocular muscle weakness --> ptosis +/- extraocular muscle weakness no myotonia normal CK and aldolase |
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central core myoapthy
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autosomal dominant due to mutations in RYR1 ryanodine receptor gene
proximal weakness and hypotonia at birth with delayed motor milestones spared facial, bulbar and ocular muscles pathology --> NADH stain shows loss of mitochondrial activity in the center of the fiber and along the entire length |
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statin-induced myopathy
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SLCO1B gene mutation associated
myalgias with or without CK increase asymptomatic CK increase weakness and rhabdomyolysis with elevated CK levels improvement with discontinuation concomitant use of fibrates increases risk of muscle toxicity |
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nemaline myopathy pathology
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nemaline bodies --> subsarcolemal rod-like structures |
