Classification of CMT

The following is a summary of the current understanding of the genetic classification of CMT.

The key point to remember is that there are two main forms of CMT:

• Demyelinating (CMT1) – affects the myelin sheath insulating and nourishing the nerve’s axon.
• Axonal (CMT2) – directly affects the axon.

The rest of the various classifications are all variations of these two main groups and, currently, will have no impact on the management of the condition.

Clinical type                     Inheritance   Locus / Gene

1. Demyelinating (CMT 1)

CMT 1A                           AD                 Duplication 17p11.2-12 / PMP-22 
                                                                                 17p11.2-12 / Point mutation PMP-22

CMT 1B                           AD                 1q22-q23 / Point mutation Po

CMT 1C                           AD                  16p13.1 - p12.3 / SIMPLE / LITAF

CMT 1D                           AD                  10q21-q22 / Point mutation EGR2

Charcot-Marie-Tooth type 1 x-linked (CMT X)

CMT X                             X-linked          Xq13.1 / Point mutation Cx32

Dejerine-Sottas disease (HMSN III)

DSD A                             AD (AR)          17p11.2-12 / Point mutation PMP-22

DSD B                             AD (AR)          1q22-q23 / Point mutation Po

DSD C                            AD                    10q21-q22 / Point mutation EGR2

Congenital hypomyelinating neuropathy (CHN)

CHN A                           AD                    17p11.2-12 / Point mutation PMP-22

CHN B                           AD                    1q22-q23 / Point mutation Po

CHN C                           AD (AR)           10q21-q22 / Point mutation EGR

Hereditary neuropathy with liability to pressure palsies (HNPP)

HNPP A                         AD                    Deletion 17p11.2 / PMP-22 17p11.2-                                                                                     12 / Point mutation PMP-22

Charcot-Marie-Tooth type 1 autosomal recessive (CMT1 AR)

CMT1 ARA (CMT4A)   AR                    8q13 - 21.1/ GDAP1

CMT1 ARB1 (CMT4B1)   AR                11q22 / MTMR2

CMT1 ARB2 (CMT4B2)   AR                11p15 / MTMR13

CMT1 ARC (CMT 4C)     AR                 5q23-q33 / KIAA1985

CMT1 ARD (CMT4D / HMSNL) AR      8q24 / NDRG1

CMT1 ARE (CCFDN)      AR                 18q

CMT1 ARF (CMT4F)      AR                  19q13.1-13.3 / Periaxin

CMT1 ARG (HMSNR)    AR                   10q22-q

2. Axonal (CMT 2) Charcot-Marie-Tooth type 2 autosomal dominant (CMT 2 / HMSN II)

CMT 2A                          AD                 1p35-KIF1B                                          
                                                                                            / GTPase mitofusin 2

CMT 2B                          AD                    3q13 – q22 / RAB7

CMT 2C                         AD                     12q23 – q24

CMT 2D                         AD                     7p14 / GARS

CMT 2E                         AD                     8p21 / NF-L

CMT 2F                         AD                     7q11-q21 / HSP 27

CMT 2G                        AD                     12q12-q13.3

CMT 2L                        AD                     12q24 / HSP 22

CMT 2                          AD                     1q22-q23 / Point mutation Po

CMT 2 (HMSNP)         AD                       3q13.1

Charcot-Marie-Tooth type 2 x-linked (CMT 2X)

CMT 2X                       X-linked              Xq24 – q26

Charcot-Marie-Tooth type 2 autosomal recessive (CMT2 AR)

CMT2 AR                    AR                      1q21.2 – 21.3 / LMNA

CMT2 AR                    AR                      19q13.1

CMT2 AR                    AR                      8q21 / GDAP1 3.

3  Dominant Intermediate CMT (DI-CMT)

DI-CMTA                   AD                       10q24.1-q25.1

DI-CMTB                   AD                        Dynamin 2

DI-CMTC                   AD                           1p34-p35

 

AD - autosomal dominant
AR - autsomal recessive

 

With thanks to Dr Mary Reilly, Consultant Neurologist from the National Hospital for Neurology, London

 

Last Updated ( Thursday, 02 July 2009 )