Continuum PNS and MND: Inherited Flashcards
Classification Scheme for Hereditary Neuropathies
HMSN (CMT) - HMN - HSAN - HNA - HSP - SCAS - Metabolic - Mitochondrial
5 MSK abnormalities seen in CMT
hammer toes, pes cavus, pes planus, cavovarus
CMT 1 (Demyelinating) CV definition
<38 m/s
Proband definition
person who brings the family under genetic study
Test for primary demyelinating inherited neuropathies
Blink Reflex R1 >13 ms latency prlongation
50% of CMT cases are…
CMT1a (demyelinating) PMP-22 duplications
CMT-De-AD (6 genes)
PMP22 - MPZ - LITAF - EGR 2 - NEFL)
Late onset CMTs
CMTJ (MPZ + Adie pupil), CMT2D - GARS1 distal UE
CMT %s De Axonal
50% Demyleinating 30% Axonal 10 % Recessive (here in cosang) X-linked 10%
Vocal cord paralysis
MFN2, TRPV4
Foot ulcerations
rab7A
HSAN2A congenital insensitivity to pain
SCN9A
dHMN v dMND v dMyopathy
markedly reduced CMAP (others slightly reduced) v MND being big units and myopathy small
Amyloid AD 3 types
TTR Gelsolin APOA1
Meds for TTR
tafamidis (oral prevents misfolding), Patisiran (small interfering RNA), Inotersen (antisense
Can repeat expansions be identified with current NGS
no
two x-linked recessive SCAs with neuropathy
Friedrichs and CANVAS (cerebellar ataxia, neuropathy, vestibular areflexia
Three Lysosomal storage disorders with neuropathy
Krabbe, Fabr, Metachromatic leukodystrophy
Mitochondrial with neuropathy
MNGIE, SANDO, MCARNE
algorithm for suspected inherited neuropathy
screening negative then ulnar CV <38 (CMAP >0.5) and/or blink reflex >13 then PMP22 –> panel then WES
Three therapeutic strategies for LOF and GOF mutations
LOF = gene replacement with AAV9 GOF RNAi or ASO
