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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: 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 + CNV: 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.