A CLINICAL APPROACH TO THE DIAGNOSIS OF COMMON UNHERITED NEUROPATHIES - PowerPoint PPT Presentation

1 / 58
About This Presentation
Title:

A CLINICAL APPROACH TO THE DIAGNOSIS OF COMMON UNHERITED NEUROPATHIES

Description:

Charcot-Marie-tooth disease (CMT) ... HMSN (CMT) CLINICAL CLASSIFICATION. I Demyelinating. II Axonal ... CLASSIFICATION OF CMT. CMT1 Demyelinating ( 38 m/s) ... – PowerPoint PPT presentation

Number of Views:1342
Avg rating:3.0/5.0
Slides: 59
Provided by: mrei3
Category:

less

Transcript and Presenter's Notes

Title: A CLINICAL APPROACH TO THE DIAGNOSIS OF COMMON UNHERITED NEUROPATHIES


1
Peripheral Nerve
2
AXONAL NEUROPATHIES
Hereditary Vasculitis Paraproteinaemic Systemic
diseases diabetes, sarcoidosis, vitamin
deficiencies, connective tissue disease, alcohol,
organ failure, malignancies Infectious Toxic Idiop
athic
3
DEMYELINATING NEUROPATHIES
Hereditary Acquired inflammatory
neuropathies Paraproteinaemic neuropathies
4
CLASSIFICATION OF THE INHERITED NEUROPATHIES
  • Neuropathies in which the neuropathy is the sole
  • or primary party of the disease
  • Neuropathoes in which the neuropathy is part of
  • a more widespread neurological or multisystem
  • disorder

5
1. HEREDITARY NEUROPATHIES (SOLE)
Charcot-Marie-tooth disease (CMT) Hereditary
neuropathy with liability to pressure palsies
(HNPP) Hereditary sensory and autonomic
neuropathies (HSAN / HSN) Familial amyloid
polyneuropathy (FAP) Hereditary motor
neuronopathies (HMN / SMA) X-linked bulbospinal
neuronopathy
6
2. HEREDITARY NEUROPATHIES (MULTISYSTEM)
Disorders of lipid metabolism Porphyrias Defecti
ve DNA repair Mitochondrial disorders Hereditary
ataxias Miscellaneous
7
IS THE NEUROPATHY HEREDITARY?
Family history Long history / slowly
progressive Foot deformity (eg. Pes
cavus) Positive sensory symptoms usually not
prominent Neurophysiology Lack of other cause /
? hereditary (esp. axonal)
8
CLASSIFICATION
Charcot-Marie-Tooth disease (CMT) Hereditary
Neuropathy with Liability to Pressure Palsies
(HNPP) Distal Hereditary Motor Neuronopathy
(dHMN / dSMA) Hereditary Sensory and Autonomic
Neuropathy (HSAN / HSN)
9
HMSN (CMT) CLINICAL CLASSIFICATION
I Demyelinating II Axonal III Severe
demyelinating / hypomyelinating IV Refsums
Disease V Pyramidal VI Optic atrophy VII
Deafness VIII Pigmentory retinopathy
10
CLASSIFICATION OF CMT
CMT1 Demyelinating ((38 m/s) CMT intermediate (30 45 m/s)
11
CLASSIFY CMT 1 (DEMYELINATING)
Demyelinating CMT 1 (Disease (Neuropathy (dysmyelination)
12
CLASSIFICATION CMT
Autosomal dominant Autosomal recessive X-linked
Sporadic
13
CLASSIFICATION CMT
CMT1 AD AR X-linked DSD AD AR CHN AD AR
HNPP AD CMT2 AD AR X-linked
14
HMSN I (CMT 1)
Slowly progressive distal wasting and
weakness Onset 1st or 2nd decade Areflexia,
distal sensory loss and foot deformity Demyelinat
ing (slow motor nerve conduction
velocities) Pathology hypertrophic, demyelinating
15
CMT 1 LEGS
16
PES CAVUS
17
HSAN I TOE
18
HSAN I FEET
19
HSAN I FEET
20
CMT 1 HANDS
21
CMT 1 ONION BULBS
22
CMT 1 TEASED FIBRES
23
CMT1 AD
CMT 1A duplication PMP-22 mutations
PMP-22 CMT 1B mutations P0 CMT 1C mutations
LITAF/SIMPLE CMT 1D mutations EGR2
24
HMSN III (DEJERINE-SOTTAS DISEASE (DSD))
Severe demyelinating / hypomyelinating
neuropathy Early onset Extremely slow motor
nerve conduction velocities Pathology
demyelination / amyelination / basal lamina
onion bulbs / classical onion bulbs
25
DEJERINE SOTTAS DISEASE (DSD)
DSD A AD/AR mutation PMP-22 DSD B
AD/AR mutation Po DSD C AD mutation EGR2 DSD
D AD 8q23 q24
26
CONGENITAL HYPOMYELINATING NEUROPATHY (CHN)
CHN A AD mutation PMP-22 CHN B AD mutation
Po CHN C AD/AR mutation EGR2
27
HNPP
Autosomal dominant Episodic, recurrent
demyelinating neuropathy Reduced motor /
sensory conduction velocities Pathology sausage
like myelin thickenings (tomacula) Linked to
chromosome 17
28
HNPP
HNPP chromosome 17 deletion PMP-22 point
mutations
29
CMT 1 AR (RECESSIVE)
CMT1 AR A (CMT4A) GDAP1
CMT1 AR B1 (CMT4B1) MTMR2
CMT1 AR B2 (CMT4B2) SBF2
CMT 1AR C SH3/TPR CMT1 AR D
(HMSNL) NDRG1 CMT1 AR E (CCFND) 18q CMT1 AR
F (CMT4F) Periaxin CMT1 AR G (HMSNR) 10q22-q2
3
30
CMT1 X-LINKED
Clinically similar to CMT1 No male to male
transmission Males more severe than
females Males demyelinating / females
axonal Patchy neurophysiology Central nervous
system involvement
31
CMT X1
Linked to Xq13.1 Gap junction protein connexin
32 in that area Mutations in connexin 32 in
X-linked HMSN I families
32
HMSN II (CMT 2)
Similar phenotype to HMSN I Later age of
onset Axonal neuropathy (normal motor nerve
conduction velocities) Patholgy axonal
33
CMT 2 (AXONAL / DOMINANT)
CMT 2A KIF1B? CMT 2B RAB7 CMT
2C unknown CMT 2D GARS CMT 2E NF-L CMT
2F 7q11-q21 CMT 2 Po CMT 2G
(HMSNP) 3q13.1
34
CMT 2 (RECESSIVE)
CMT2 AR A LMNA CMT2 AR B 8q21.3 CMT2 AR
C 19q13.3 CMT2 AR D GDAP1
35
CMT 2 (X-LINKED)
CMT 2X Xq24 - 26
36
INTERMEDIATE CMT
CX 32 PO GDAP1 ?NFL DI CMT 10q24.1-q25.1 DI
CMT 19p12-p13
37
Peripheral nerve
38
(No Transcript)
39
(No Transcript)
40
(No Transcript)
41
(No Transcript)
42
(No Transcript)
43
(No Transcript)
44
(No Transcript)
45
(No Transcript)
46
Peripheral Nerve
47
(No Transcript)
48
(No Transcript)
49
(No Transcript)
50
(No Transcript)
51
Peripheral Nerve
52
(No Transcript)
53
(No Transcript)
54
MOLECULAR DIAGNOSIS
Chromosome 17 duplication / deletion widely
available PMP-22, P0 and CX-32 specialised
laboratories EGR2, NF-L, KIFIBß, MTMR2, NDRG1,
Periaxin, GDAP1, LMNA research laboratories only
55
CMT DIAGNOSIS FLOW CHART
56
WHY DIAGNOSE CMT ?
Definite diagnosis Prognosis Prevents
unnecessary tests (eg. Nerve biopsy) Genetic
counselling family / diagnostic / predictive /
ante-natal Treatment therapy / orthopaedic
57
TREATMENT OF CMT
Gene therapy
58
CMT GENE THERAPY
Transgenic mouse study CMT 1A Regulation of
PMP-22 overexpression possible Overexpression
causes demyelination Demyelination corrected
when ovexpression turned off
Write a Comment
User Comments (0)
About PowerShow.com