Publications about genetic testing for neurological disorders
  1. Charcot–Marie–Tooth (CMT) neuropathy gene panel

Charcot–Marie–Tooth (CMT) neuropathy gene panel

June 08, 2018

Disease summary:

Charcot-Marie-Tooth (CMT) disease is a group of hereditary neuropathies, and represents one of the most common neurological conditions, characterized by a chronic motor and sensory polyneuropathy.

CMT is divided into the primary demyelinating neuropathies (CMT1, CMT3, and CMT4) and the primary axonal neuropathies (CMT2), with significant clinical overlap. All CMT subtypes are hereditary and >100 genes have been associated with CMT (Table 1) 1, 2.                   

The most common cause of CMT (70–80% of the cases) is the duplication of a large region on the short arm of chromosome 17 that includes gene PMP223, 4


Autosomal recessive, X-linked recessive, rarely autosomal dominant

Major clinical symptoms 1, 2:

  • Slowly progressive distal muscle weakness in the feet and/or hands
  • Variable age of onset
  • Difficulties walking, frequent tripping, falls
  • High-arched feet, weak ankle dorsiflexion, foot drop, pes cavus
  • Poor hand control, difficulties writing
  • Depressed tendon reflexes
  • Distal sensory loss
  • Presence of the specific clinical features (distal muscle weakness, sensory loss)
  • Positive family history of disease
  • Characteristic findings on electro-myographic (EMG) tests
  • Specific findings on nerve biopsy
  • Identification of pathogenic variant in one of the associated genes (Table 1)

There is no cure for Charcot-Marie-Tooth disease and other hereditary neuropathies but numerous symptomatic treatments exist, including the following 1, 4:

  • Management by a multidisciplinary team of neurologists, orthopedic surgeons, physical and occupational therapists
  • Special shoes and ankle/foot orthoses
  • Orthopedic surgery as needed for severe pes cavus
  • Pain-relief medication, carbamazepine or gabapentin for neuropathic pain.
  • Hereditary neuropathy with liability to pressure palsies (HNPP) caused by deletions in PMP22
  • CMT syndrome with spasticity caused by pathogenic variants in BSCL2, SPART or other genes
  • Familial brachial plexus neuropathy caused by pathogenic variants in SEPT9
  • Amyloid neuropathies caused by pathogenic variants in TTR and other genes
  • Refsum disease caused by pathogenic variants in PEX7 or PHYH
  • Metachromatic leukodystrophy caused by pathogenic variants in ARSA
  • Krabbe disease caused by pathogenic variants in GALC
  • Friedreich ataxia caused by pathogenic variants in FXN
  • X-linked disorders with neuropathy (Pelizaeus-Merzbacher disease, Adrenomyeloneuropathy)
  • Diabetes mellitus
  • Thyroid disease
  • Alcoholism
  • Vitamin B12 deficiency

To confirm/establish the diagnosis of CMT, CENTOGENE offers the following tests:

  • PMP22 gene deletion/duplication analysis
  • CMT neuropathy NGS Panel Plus: full gene sequencing of the genes AARS, AIFM1, ARHGEF10, BSCL2, COX6A1, DHTKD1, DNAJB2, DNM2, DNMT1, DYNC1H1, EGR2, FAM134B, FBLN5, FGD4, FIG4, GAN, GARS, GDAP1, GJB1, GNB4, HINT1, HK1, HOXD10, HSPB1, HSPB8, IGHMBP2, IKBKAP, INF2, KARS, KIF1B, KIF5A, LITAF, LMNA, LRSAM1, MARS, MED25, MFN2, MPZ, MTMR2, NDRG1, NEFL, PDK3, PLEKHG5, PMP22, PRPS1, PRX, RAB7A, REEP1, SBF1, SBF2, SH3TC2, TRIM2, TRPV4, VCP, YARS
  • CMT neuropathy panel NGS Panel Plus + CNV: full gene sequencing and additionally detection of large deletions and duplications from the NGS data
  • Individuals with a positive family history of CMT disease
  • Individuals with most common symptoms of CMT disease (regardless of family history)

Confirmation of a clinical diagnosis through genetic testing of CMT disorder can allow for genetic counseling and may direct medical management.


Table 1. Overview of the genes in CENTOGENE´s CMT disorder panel:

GeneOMIM gene Disease OMIM disease InheritanceLocus
AARS 601065 Charcot-Marie-Tooth disease, axonal, type 2N      
Epileptic encephalopathy, early infantile, 29 
613287 616339AD, AR16q22
AIFM1 300169

Combined oxidative phosphorylation deficiency 6   Cowchock syndrome

Deafness, X-linked 5

300816

300614

310490
XLR Xq26.1
ARHGEF10 608136 Slowed nerve conduction velocity       608236AD8p23.3
BSCL2 606158 Encephalopathy, progressive, with or without lipodystrophy

Lipodystrophy, congenital generalized, type 2

Neuropathy, distal hereditary motor, type VA

Silver spastic paraplegia syndrome 
615924

269700

600794

270685
AD, AR11q12.3
COX6A1 602072 Charcot-Marie-Tooth disease, recessive intermediate D  616039AR12q24.31
DHTKD1 614984 2-aminoadipic 2-oxoadipic aciduria
Charcot-Marie-Tooth disease, axonal, type 2Q 
204750
615025
AR10p14
DNAJB2 604139 Spinal muscular atrophy, distal, 5         614881AR2q35
DNM2 602378

Centronuclear myopathy 1                   

Charcot-Marie-Tooth disease, axonal type 2M

Lethal congenital contracture syndrome 5  

160150

606482

615368
AD, AR19p13.2
DNMT1 126375 Cerebellar ataxia, deafness, and narcolepsy
Neuropathy, hereditary sensory, type IE 
604121
614116
AD19p13.2
DYNC1H1 600112 Charcot-Marie-Tooth disease, axonal, type 20

Mental retardation, autosomal dominant 13

Spinal muscular atrophy, lower extremity-predominant 1 

614228

614563

158600
AD14q32.31
EGR2 129010 Charcot-Marie-Tooth disease, type 1D

Dejerine-Sottas disease

Neuropathy, congenital hypomyelinating, 1           

607678

145900

605253
AD, AR10q21.3
FAM134B 613114 Neuropathy, hereditary sensory and autonomic, type IIB            613115AR5p15.1
FBLN5 604580

Neuropathy, hereditary, with or without age-related macular degeneration

Cutis laxa, autosomal dominant 2      

Cutis laxa, autosomal recessive, type IA                  

Macular degeneration, age-related, 3 

608895

614434

219100

608895
AD, AR14q32.12
FGD4 611104 Charcot-Marie-Tooth disease, type 4H  609311AR12p11.21
FIG4 609390 Charcot-Marie-Tooth disease, type 4J                                              

Polymicrogyria, bilateral temporooccipital

Amyotrophic lateral sclerosis 11

Yunis-Varon syndrome    

611228

612691

612577

216340
AD, AR6q21
GAN 256850 Giant axonal neuropathy-1  256850AR16q23.2
GARS 600287 Charcot-Marie-Tooth disease, type 2D
Neuropathy, distal hereditary motor, type VA        

601472

600794
AD7p14.3
GDAP1 606598 Charcot-Marie-Tooth disease, axonal, type 2K

Charcot-Marie-Tooth disease, axonal, with vocal cord paresis Charcot-Marie-Tooth disease, recessive intermediate, A

Charcot-Marie-Tooth disease, type 4A 
607831

607706

608340

214400
AD, AR8q21.11
GJB1 304040 Charcot-Marie-Tooth neuropathy, X-linked dominant, 1              302800XLDXq13.1
GNB4 610863 Charcot-Marie-Tooth disease, dominant intermediate F  615185AD3q26.33
HINT1 601314 Neuromyotonia and axonal neuropathy, autosomal recessive  137200AR5q23.3
HK1 142600

Neuropathy, hereditary motor and sensory, Russe type

Hemolytic anemia due to hexokinase deficiency

Retinitis pigmentosa 79 

605285

235700

617460
AR10q22.1
HOXD10 142984 Charcot-Marie-Tooth disease, foot deformity of; Congenital pes valgus 192950AD2q31.1
HSPB1 602195 Charcot-Marie-Tooth disease, axonal, type 2F       
Neuropathy, distal hereditary motor, type IIB         

606595

608634
AD7q11.23
HSPB8 608014 Charcot-Marie-Tooth disease, axonal, type 2L
Neuropathy, distal hereditary motor, type IIA         

608673

158590
AD12q24.23
IGHMBP2 600502 Charcot-Marie-Tooth disease, axonal, type 2S
Neuronopathy, distal hereditary motor, type VI 
616155
604320
AR11q13.3
IKBKAP 603722 Dysautonomia, familial  223900AR9q31.3
INF2 610982 Charcot-Marie-Tooth disease, dominant intermediate E
Glomerulosclerosis, focal segmental, 5 
614455
613237
AD14q32.33
KARS 601421 Charcot-Marie-Tooth disease, recessive intermediate, B
Deafness, autosomal recessive 89     
613641
613916
AR16q23.1
KIF1B 605995 Charcot-Marie-Tooth disease, type 2A1

Pheochromocytoma       

Neuroblastoma, susceptibility to, 1 

118210

171300

256700
AD, IC1p36.22
KIF5A 602821 Myoclonus, intractable, neonatal

Spastic paraplegia 10, autosomal dominant

Amyotrophic lateral sclerosis, susceptibility to, 25
617235

604187

617921
AD12q13.3
LITAF 603795 Charcot-Marie-Tooth disease, type 1C  601098AD16p13.13
LMNA 150330 Charcot-Marie-Tooth disease, type 2B1

Cardiomyopathy, dilated, 1A

Emery-Dreifuss muscular dystrophy 2

Emery-Dreifuss muscular dystrophy 3

Hutchinson-Gilford progeria

Malouf syndrome             

Mandibuloacral dysplasia

Muscular dystrophy, congenital          

Muscular dystrophy, limb-girdle, type 1B

Restrictive dermopathy, lethal             

605588

115200

181350

616516

176670

212112

248370

613205

159001

275210
AD, AR1q22
LRSAM1 610933 Charcot-Marie-Tooth disease, axonal, type 2P         614436AD, AR9q33.3-q34.1
MARS 156560 Charcot-Marie-Tooth disease, axonal, type 2U
Interstitial lung and liver disease 
616280
615486
AD, AR12q13.3
MED25 610197 Charcot-Marie-Tooth disease, type 2B2
Basel-Vanagait-Smirin-Yosef syndrome 

605589

616449
AR19q13.33
MFN2 608507

Charcot-Marie-Tooth disease, axonal, type 2A2A

Charcot-Marie-Tooth disease, axonal, type 2A2B

Hereditary motor and sensory neuropathy VIA      

609260

617087

601152
AD, AR1p36.22
MPZ 159440

Charcot-Marie-Tooth disease, dominant intermediate D Charcot-Marie-Tooth disease, type 1B         

Charcot-Marie-Tooth disease, type 2I                       

Charcot-Marie-Tooth disease, type 2J                      

Dejerine-Sottas disease                                                 

Neuropathy, congenital hypomyelinating               

Roussy-Levy syndrome 

607791

118200

607677

607736

145900

605253

180800
AD, AR1q23.3
MTMR2 603557 Charcot-Marie-Tooth disease, type 4B1  601382AR11q21
NDRG1 605262 Charcot-Marie-Tooth disease, type 4D  601455AR8q24.22
NEFL 162280 Charcot-Marie-Tooth disease, dominant intermediate G

Charcot-Marie-Tooth disease, type 1F                      

Charcot-Marie-Tooth disease, type 2E                       

617882

607734

607684
AD, AR8p21.2
PDK3 300906 Charcot-Marie-Tooth disease, X-linked dominant, 6  300905XLDXp22.11
PLEKHG5 611101 Charcot-Marie-Tooth disease, recessive intermediate C
Spinal muscular atrophy, distal, autosomal recessive, 4 

615376

611067
AR1p36.31
PMP22 601097

Charcot-Marie-Tooth disease, type 1A                     

Charcot-Marie-Tooth disease, type 1E                      

Neuropathy, inflammatory demyelinating

Dejerine-Sottas disease

Neuropathy, recurrent, with pressure palsies

Roussy-Levy syndrome 

118220

118300

139393

145900

162500

180800
AD, AR17p12
PRPS1 311850 Charcot-Marie-Tooth disease, X-linked recessive, 5

Arts syndrome

Deafness, X-linked 1

Phosphoribosylpyrophosphate synthetase superactivity 

311070

301835

304500

300661
XLRXq22.3
PRX 605725 Charcot-Marie-Tooth disease, type 4F                      
Dejerine-Sottas disease 

614895

145900
AD, AR19q13.2
RAB7A 602298 Charcot-Marie-Tooth disease, type 2B  600882AD3q21.3
REEP1 609139

Neuronopathy, distal hereditary motor, type VB

Spastic paraplegia 31      

614751

610250
AD2p11.2
SBF1 603560 Charcot-Marie-Tooth disease, type 4B3  615284AR22q13.33
SBF2 607697 Charcot-Marie-Tooth disease, type 4B2  604563AR11p15.4
SH3TC2 608206 Charcot-Marie-Tooth disease, type 4C                      
Mononeuropathy of the median nerve, mild           

601596

613353
AD, AR5q32
TRIM2 614141 Charcot-Marie-Tooth disease, type 2R  615490AR4q31.3
TRPV4 605427 Hereditary motor and sensory neuropathy, type IIc

Scapuloperoneal spinal muscular atrophy              

Spinal muscular atrophy, distal, congenital nonprogressive

Avascular necrosis of femoral head, primary, 2    

Brachyolmia type 3         

Digital arthropathy-brachydactyly, familial                                    

Metatropic dysplasia       

Parastremmatic dwarfism

SED, Maroteaux type      

Spondylometaphyseal dysplasia, Kozlowski type 

606071

181405

600175

617383

113500

606835

156530

168400

184095

184252
AD12q24.11
VCP 601023

Charcot-Marie-Tooth disease, type 2Y                      

Amyotrophic lateral sclerosis 14, with or without frontotemporal dementia                      

Inclusion body myopathy with early-onset Paget disease and frontotemporal dementia 1 

616687

613954

167320
AD9p13.3
YARS 603623 Charcot-Marie-Tooth disease, dominant intermediate C  608323AD1p35.1