Neurological/Neuromuscular Flashcards
elevated VLCFA
20% females with spastic paraparesis
X-linked
X-linked Adrenoleukodystrophy
- ABCD1*
- 3 types:*childhood, adrenomyeloneuropathy, Addison’s dosease only
Corticosteroid replacment
Bone Marrow transplant; supportive care
post mortum: beta amyloidneuotic plaques
intraneuronal neurofibrillary tangles
amyloid angiopathy
early onset familial Alzheimer’s Disease
PSEN1, APP, PSEN2
APOE e4 assoc/APOE e2 protection: Late onset familial Alzheimer’s Disease
loss of maternall imprinted contribution
15q11.2-q13
Angelman Syndrome
stroke like episodes before the age of 60
cognitive disturbance
behavioral abnormalities
migraine with aura
CADASIL
Cerebral Autosomal Dominant Arteriopathy with subcortical infarcts and Leukoencephalopathy
NOTCH3
macrocephaly developmental delay
hypotonia progressing to spacticity
increase urine NAA (N- acetyl aspartic acid)
abscence of aspartoacylase
Canavan Disease
- ASPA*
- Autosomal Recessive*
AJ ancestry
smooth tongue without typical vascularized fungiform papulae
Familial dysautonomia
X-linked
CGG triplet repeat
silencing of methylation
Fragile X
CAG repeat expansion
36-39: reduce penetrance
>40: full penetrance
>60 juvinille onset
Huntington Disease
- GALC*
- AR*
Galactocerebrosidase def
Krabbe Disease
low serum Cu and ceruloplasmin
high urinary excretion of Cu
Bx: increase liver Cu storage
Kayser-Fleisher rings
Wilson Disease
ATP7B
Loss of function
- impaired holoceruloplasmin biosynthesis and biliary excretion of copper
- copper mediated oxidative stress
- cell death
- leakage of copper into the plasma
- copper over load of tissue
CDKL5
Rett syndrome
small subset present atypically with early onset seizures
Rett Syndrome
normal function of MECP2
binds methylated CpG Islands
loss of motor neurons: UMN and LMN signs
CN VII, XI, X
toxic gain of function
- SOD1*
- Tx:* Riluzole
Amyotrophic Lateral Sclerosis
- PMP22*
17p11. 2
Duplication
nerve biopsy: segmental demyelination, myelin sheath hypertrophy
dominant negative mutations/increase dosage
Charcot Marie Tooth
CMT1A
progressive distal muscle weakness and muscle wasting
hyporeflexia
abnormal nerve condution sydies
De novo duplications (20-30%): 90% arise during male meiosis
Reciprocal deletion : Herediatary neuropathy with pressure palsies (HNPP)
Eteplirsen
antisensense oligonucleotide
induce exon skipping (exon 51)
Tx: DMD
abnormal expanded GAA repeat in intron 1
2/3 have cardiomyopathy
30% have DM
Friedreich ataxia
FXN gene
AR inheritance
Loss of function of fratatxin
full mutation >66
normal rpt: 5-33
walk on tiptoes
difficulty running
scapular winging
waddling gait
slight hyperlordosis
elevated serum CK
Calpinopathy
AR Inheritance
CAPN3 gene
increase muscle irritability
percussion induced rapid contaction
percussion induced muscle mounding
Caveolinopathy- rippling muscle disease
AD inheritance
CAV3 gene
CTG triplet repeats in 3’-UTR
cataracts/mytonia
arrhythmias
grip myotonia
respiratory distress
gain of function RNA mechanism
PCR can only detect repeats ~100 repeats
Southern blot can detect >100 repeats
Myotonic Dystrophy Type 1
DMPK gene
AD inheritance
multisystem condition
Mild: 5-150 repeats
Classic: 100-1000 repeats
Congenital: > 2000
Muscle biopsy: rod shaped structures
stained with Gomori trichrome
Nemaline Myopathy
hypotonia, weakness, depressed or absent deep tendon reflex
6 types overlap
Amish type
walking before 18 months predictive of survival
Spinal Muscular Atrophy
- Increase in SMN2 copy number can modify the _______
- SMN2 lacks exon ___
- Tx: Spinraza/Nusinersen: ______RNA lead to induction of exon ___ in the SMN2 transcript
- Carriers of 2 copies of SMN1 in ___ will be misdiagnosed as non-carriers
- Phenotype
- 7
- Anti-sense ; 7
- cis
- Exon 7 of SMN1: undetectable in > 95% irrespective of clinical subtype*
- SMN1 (telomeric)*
- SM2 (centromeric)*
Hypotonia
Symetric generalized weakness
CNS migration distubances: Cobblestone Lissencephaly
elevated CK
microcorne/microphthalmia,cataracts,retinal dysplasia/detachment
Syndromic Congenital Muscular Dystrophy
Fukuyama: FKTN
Muscle-eye-brain: POMGNT1
Walker-Warburg: POMT1, POMT2
Congenital Muscular Dystrophy Type 1D : LARGE
seizures
vision loss
exagerated startle
progressive neurogeneration
cherry red spot on eye exam
Tay-Sachs Disease
Hexosaminidase A deficiency results in a group of neurodegenerative disorders caused by intralysosomal storage of the specific glycosphingolipid, GM2 ganglioside.
The diagnosis of hexosaminidase A deficiency relies on the demonstration of absent to near-absent beta-hexosaminidase A (HEX A) enzymatic activity in the serum or white blood cells of a symptomatic individual in the presence of normal or elevated activity of the beta-hexosaminidase B (HEX B) isoenzyme.
HEXA common mutation panel: 92% Ashkenazi Jewish
WHat percentage of individuals with Huntington disease can be affected by suicidal behaviour?
Suicidal behavior, in particular, can affect up to 20% of symptomatic and pre-symptomatic patients. Suicide is 12 times more frequent among Huntington’s patients compared to the general population
Suicide affects about 12% of individuals with HD
