Neuro Flashcards
(27 cards)
Early onset alzheimers:
AD, PSEN1 (20-70%), PSEN2, APP (10-15%)
onset <60y
1-6% of all alzheimer cases
Late onset alzheimers: APOE e4 variant is associated, but not specific. APOE e2 might be protective
Angelman syndrome:
15q11q13 del/UPD, UBE3A
loss of maternal 15q
normal at birth, but severe DD, ID, ataxia, happy demeanor, light hair and eye color
progressive microcephaly, seizures
CADASIL:
AD, NOTCH3
(Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy)
stroke-like episodes <60y, cognitive disturbance, migraines (30’s)
dx: brain MRI: T2 subcortical lacunar lesions, white matter changes seen by early 20’s
Canavan disease:
AR, ASPA
macrocephlay, lack of head control, DD, hypotonia, never able to sit, walk or speak
hypotonia progresses to spasticity
dx; high urine n-acetyl aspartic acid (NAA)
3 comman variants seen in 99% of AJ cases
mechanism: absence of enzme> high NAA> demyelination
Familial dysautonomiax
Familial dysautonomia: AR, ELP1
neurodegeneration, GI dysfunction, altered pain/temp sensitivity, autonomic crisis,
decreased taste & papillae on tongue
2 common varaints in AJ= 99% of cases
dx: pupillary hypersensitivity to parasympathetic agents
Fragile-X:
CGC expansion in FMR1
ID, prominent ears, triangular face, macroorchidism, seizures
prominent jaw& forehead
premutation- results in increased mRNA, full mutation- silencing of gene
Premutation carrier females: 20% have primary ovarian insuff.
Fragile-X ataxia: a/w premutation: ataxia, tremors, parkinsonism- both males and females can be affected
Full mutation- not really a risk for FXPOI or FX ataxia since there’s a diff. mechanism
Normal: <44 repeats
Intermediate: 45-54
Pre-mutation: 55-200
Full-mutation: >200
AGG repeats reduce expansion risk
Huntinton disease:
AD, HTT (CAG expansion)
progressiv motor disease (chorea, dystonia), cognitive decline, psych disturbance
onset 35-44y, but can be juvenile <20y
Normal: <26 repeats
Intermediate: 27-35
Path (reduced pen): 36-39
PATH (full pen): >40
Juvenile onset: >60
NF1:
AD
NF1 inhibits RAS signaling
>6 CALMS, >2 neurofibromas, axilllary or inguinal freckling, optic glioma, lisch nodules (brown spots in iris)
Cancer: nerve sheath tumors, breast, optic glioma, pheo, leukemias
plexiform neurofibromas: benign, but high morbidity. Disfiguring and can be life threatening if big enough; can transform into nerve sheath tumor
cancer screening: routine screening NOT done
bone: long bone dysplasia
tx: MEK inhib (selumetinib)
Parkinson disease:
Mostly multifactorial, but know PARK2 and GBA (Gaucher)
bradykinesia, rigidity, tremor
tx: L-dopa
Rett syndrome:
XD, MECP2
Dev. regression, microcephaly, hand wringing, paroxysmal laughing, prolonged QT, scoliosis, gait instability
small subset have CDKL5 (can present as Rett, but usually as DEE) variants instead
tx: trofinetide: IGF1 3 aa peptide (mechanism unclear), promotes neuron survival
Wilson disease:
AR, ATP7B
onset 3-50y
hepatitis & jaundice, kayser-fleisher rings in eye
Neuro: movement dx, psychiatric disturbances
dx: low serum copper
tx: chelating agents
Late onset Alzheimer’s
APOE e4 allele
but we don’t really test for this, absolute risk of e4 allele isn’t that high (25-30% if hom)
ALS/FTD:
AD C9ORF72 GGGGCC repeat exp, SOD1 ms
SOD1 tx: FDA approved ADO knockdown w/ tofersen
Sturge Weber:
GNAQ- mosaic
somatic mosaic only- not heritable
same variant causes port wine stain
port wine stain on face, abnormal cerebral blood flow> seizures & stroke & brain atrophy, glaucoma
PWS on forehead- highest risk for sturge weber
Double cortex syndrome:
DCX, XL
females:: subcortical band heterotopia
Males: lissencephaly
caused by abnormal neuron migration
Miller-dieker:
del of LIS1 (17p13.3)
lissencephaly, facial dysmorphisms, kidney issues
Periventricular nodular heterotopia-
FLNA (XD)
likely a girl
gray matter in wrong areas
ALS:
AD: C9orf72; AD/AR SOD1
Upper motor: hyperreflexia, inc. tone, weakness
lower moter; weakness, muscle wasting, hyporeflexia
Dementia
Mechanism: toxic GOF
Charcot Marie Tooth
CMT1 (50%): demyelinating (PMP22)
CMT2 (20-40%): non-demyelinating
progressive weakness of distal muscles in 1st-3rd decade, hearing loss, hip dysplasia
pes cavus, finger contractures
Duchenne Muscular dystrophy;
DMD, XR
DMD: progressive muscle weakness (Gower sign), proximal>distal, calf hypertrophy, cardiomyopathy
Becker: later onset, less severe, weakness of quads may be only sign
dx: very high CK conc.
DMD= NMD and loss of protein, Becker=in-frame dels
Treatment: ASO exon skipping (casimersen) or gene therapy
difference b/t SMA: boy, high CK, muscle pseudohypertrophy, and usually older than in SMA
Friedrich Ataxia:
AR, FXN
progressive limb and gait ataxia <25y, hyporeflexia
within 5 yrs of onset, dysarthria, areflexia, leg weakness, cardiomyopathy, neuropathy
starts in teen years
GAA repeat expansion in intron 1
Normal <33
Premutation: 34-65
Path: 66-1300
tx: Omaveloxolone: activates antioxidant stress response- turns on cell protective response
Hereditary neuropathy w/ liability to pressure palsies:
AD PMP22
Adult onset, recurrent pressure palsies, polyneuropathy, absent ankly reflex, pes cavus
PMP22 del (80%) is common
Limb Girdle Muscular dystrophy:
Mostly AR, multiple genes
Sarcoglycan LGMD: proximal weakness, calf hypertrophy, onset 3-5y
Calpain LGMD: same as above, onset 2-20y
Dysferlin LGMD: distal weakness, onset 15-25y
dx. inc. CK
tx: supportive, but monitor for cardiomyopathy
Myotonic Dystrophy type 1:
AD, DMPK
Normal (5-34 repeats)
Premutation (35-49 repeats)
Mild (50-150 repeats): cataracts, mild myotonia
Classic (100-1000): weakness, myotonia, cataract, arrhythmia
Congenital (>1000x): hypotonia, severe weakness, resp insufficiency
CTG repeats in 3’ UTR, toxic GOF; anticipation occurs
