Week 5: Neuromuscular disorders Flashcards
Tell me about myotonic dystrophy
-Multisystem disorder affecting skeletal and smooth muscle, eye, heart, endocrine, CNS
3 phenotypes:
1. Classic: muscle weakness and wasting, cataracts, myotonia, cardiac conduction abnormalities, physical disability, possibly shortened lifespan, endocrine issues
2. Mild: cataract, mild myotonia, diabetes, normal lifespan
3. Congenital: hypotonia and severe weakness at birth, respiratory insufficiency, early death, surviving infants usually able to walk, ID
-Symptoms of congenital DM1: severely hypotonic at birth, contractures, poor suck and swallow, frequently need respiratory support, have slowed motor and mental development, high neonatal mortality rate
-AD repeat expansion for DMPK gene (aka DM1)
-Correlation exists between size of expansion and age of onset/severeity
-ZNF9 (now called CNBP) gene in rare cases (aka DM2)
-DM2: tetranucleotide repeat expansion
-No correlation between repeat size and severity
Feeding, tone, and respiratory all tend to improve as age
Tell me about SMA
-Clinical features: hypotonia, progressive muscle weakness, areflexic, intelligent children, tongue fasciculations, finger tremors
-Respiratory/bulbar involvement usually cause of mortality
-Extraocular and facial muscles spared
-SMN1
Tell me about Duchenne and Becker MD
-Involved dystrophin gene, most common mutations are gene deletions
-If deletion out of frame=Duchenne=absence of dystrophin
-If in frame deletion=Becker=dysfunctional dystrophin
-Female carriers are symptomatic ~10% cases
-Testing typically involves del/dup analysis and then sequencing as a secondary
Tell me a little bit about Charcot Marie Tooth disease
-Affects both motor and sensory nerves
-Symptoms: typically symmetrical and involve the senses, peripheral (or poly) neuropathy, often appears distally
-Demyelination and axonal degeneration
-Dx made by neurological exam, nerve conduction study, fhx
-4 subtypes
-Genetics: several genes, AD/AR/XL, most common PMP22 (duplication testing common) AD form
-Nerve conduction study necessary for dx MUST be abnormal
Describe what a EMG and a NCS analysis is
EMG
-The recording and study of insertion, spontaneous, and voluntary activity of muscle with a recording electrode (surface or needle)
-Checking if nerves responding correctly to signals
NCS
-Recording and analysis of electric waveforms of biologic origin elicited in response to electric or physiologic stimuli
-Check for damage/disease
What can a EMG/NCS tell you?
-Differentiate between myopathic vs neuropathic forms of disease
-In neuropathic forms can differentiate between axonal and demyelinating disease
-Whether or not nerve regeneration present
-Finds myotonic discharges
Can NOT tell you:
-May not show any change in early course or mild forms of disease
-Can be limited by patient tolerance and location of analysis
-Can’t pick up small fiber neuropathies
What are a few reasons we might perform a muscle biopsy?
-Differential dx narrowing
-Mito function/DNA
-Clarify genetic testing results
-Suspicion for inflammatory neuropathy
-Research
True or false: NGS (WES or WGS) can identify nucleotide repeat expanisions
False!
Tell me about spinocerebellar ataxia
-AD hereditary ataxia
-Causes of ataxia: hereditary (must have 1 or more: dysfunction of the cerebellum, spinal cord lesions, peripheral sensory loss) and acquired (stoke, alcoholism, vita deficiency, MS, cancer, metabolic disorders)
-Variable presentation, cannot be accurately predicted by fhx
-chronic and degenerative
-Gene: SCA1, trinucleotide repeat
What’s the pneumonic for hereditary ataxia/SCA
DANISH
D: dysmetria (lack of coordination) and dysdiadochokinesia (inability to perform coordinated, rapid movements)
A: ataxia (slowly progressive incoordination of gait, hands, speech, etc)
N: Nystagmus
I: intention tremor
S: slurred speech
H: hyperreflexia (exaggeration of reflexes)
Tell me about Huntington’s disease
-Progressive disorder of involuntary movements, cognitive decline, personality and mood disturbances
-Adult onset (>90% cases): symptoms between 30-40s
-Juvenile onset: symptoms in childhood or teens
-Dx in a symptomatic person is made off of clinical findings, fhx and when possible genetic testing results
-Not having genetic testing does not remove a clinical dx of Huntington’s
Features:
-Behavior changes
-Abnormal movements
-Memory impairment
-Rigidity
-Anxiety, stress, tension
-Difficulty swallowing
-Speech impairment
Genetics:
-HTT gene, trinucleotide expansion
-AD
-Full penetrance: 40+ repeats
-Reduced penetrance: 36-39 repeats
+May be at risk for developing HD but may not develop symptoms
-Intermediate: 27-35 repeats
+NOT at risk to develop HD, offspring may have HD
-Normal: 26 or less repeats
Is anticipation more common from male or female parent for HD?
Male, uncommon for female transmission
