Format

Send to:

Choose Destination

Charcot-Marie-Tooth disease type 2D(CMT2D)

MedGen UID:
316946
Concept ID:
C1832274
Disease or Syndrome
Synonyms: Charcot-Marie-Tooth disease, axonal, Type 2D; Charcot-Marie-Tooth disease, neuronal, Type 2D; Charcot-Marie-Tooth Neuropathy Type 2D; Charcot-Marie-Tooth Neuropathy Type 2D (CMT2D); CMT 2D; CMT2D
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Sources: HPO, OMIM, Orphanet
Autosomal dominant inheritance refers to genetic conditions that occur when a mutation is present in one copy of a given gene (i.e., the person is heterozygous).
Autosomal dominant inheritance (HPO, OMIM, Orphanet)
 
Gene (location): GARS (7p14.3)
OMIM®: 601472
Orphanet: ORPHA99938

Definition

GARS-associated axonal neuropathy (Charcot-Marie-Tooth neuropathy type 2D/distal spinal muscular atrophy V [CMT2D/dSMA-V]) is characterized by adolescent or early-adult onset of bilateral weakness and atrophy of thenar and first dorsal interosseus muscles, sparing of the hypothenar eminence until later in the course of illness, and mild to moderate impairment of vibration sense in the hands and feet later in the disease course in a minority of individuals. The phenotype is considered the CMT2D subtype when sensory deficits (reduction of pinprick, temperature, touch, and vibration perception in a stocking and [less often] glove pattern) are present and dSMA-V when sensory deficits are absent. The lower limbs are involved in about half of affected individuals. The earliest elicited manifestations in many individuals are transient cramping and pain in the hands on exposure to cold and cramping in calf muscles on exertion. [from GeneReviews]

Additional description

From GHR
Charcot-Marie-Tooth disease is a group of progressive disorders that affect the peripheral nerves. Peripheral nerves connect the brain and spinal cord to muscles and to sensory cells that detect sensations such as touch, pain, heat, and sound. Damage to the peripheral nerves can result in loss of sensation and wasting (atrophy) of muscles in the feet, legs, and hands.Charcot-Marie-Tooth disease usually becomes apparent in adolescence or early adulthood, but onset may occur anytime from early childhood through late adulthood. Symptoms of Charcot-Marie-Tooth disease vary in severity, even among members of the same family. Some people never realize they have the disorder, but most have a moderate amount of physical disability. A small percentage of people experience severe weakness or other problems which, in rare cases, can be life-threatening. In most affected individuals, however, Charcot-Marie-Tooth disease does not affect life expectancy.Typically, the earliest symptoms of Charcot-Marie-Tooth disease involve balance difficulties, clumsiness, and muscle weakness in the feet. Affected individuals may have foot abnormalities such as high arches (pes cavus), flat feet (pes planus), or curled toes (hammer toes). They often have difficulty flexing the foot or walking on the heel of the foot. These difficulties may cause a higher than normal step (or gait) and increase the risk of ankle injuries and tripping.As the disease progresses, muscles in the lower legs usually weaken, but leg and foot problems rarely require the use of a wheelchair. Affected individuals may also develop weakness in the hands, causing difficulty with daily activities such as writing, fastening buttons, and turning doorknobs. People with this disorder typically experience a decreased sensitivity to touch, heat, and cold in the feet and lower legs, but occasionally feel aching or burning sensations. In some cases, affected individuals experience gradual hearing loss, deafness, or loss of vision.There are several types of Charcot-Marie-Tooth disease. Type 1 Charcot-Marie-Tooth disease (CMT1) is characterized by abnormalities in myelin, the fatty substance that covers nerve cells, protecting them and helping to conduct nerve impulses. These abnormalities slow the transmission of nerve impulses. Type 2 Charcot-Marie-Tooth disease (CMT2) is characterized by abnormalities in the fiber, or axon, that extends from a nerve cell body and transmits nerve impulses. These abnormalities reduce the strength of the nerve impulse. Type 4 Charcot-Marie-Tooth disease (CMT4) affects either the axon or myelin and is distinguished from the other types by its pattern of inheritance. In intermediate forms of Charcot-Marie-Tooth disease, the nerve impulses are both slowed and reduced in strength, probably due to abnormalities in both axons and myelin. Type X Charcot-Marie-Tooth disease (CMTX) is caused by mutations in a gene on the X chromosome, one of the two sex chromosomes. Within the various types of Charcot-Marie-Tooth disease, subtypes (such as CMT1A, CMT1B, CMT2A, CMT4A, and CMTX1) are distinguished by the specific gene that is altered.Sometimes other, more historical names are used to describe this disorder. For example, Roussy-Levy syndrome is a form of Charcot-Marie-Tooth disease defined by the additional feature of rhythmic shaking (tremors). Dejerine-Sottas syndrome is a term sometimes used to describe a severe, early childhood form of Charcot-Marie-Tooth disease; it is also sometimes called Charcot-Marie-Tooth disease type 3 (CMT3). Depending on the specific gene that is altered, this severe, early onset form of the disorder may also be classified as CMT1 or CMT4. CMTX5 is also known as Rosenberg-Chutorian syndrome. Some researchers believe that this condition is not actually a form of Charcot-Marie-Tooth disease. Instead, they classify it as a separate disorder characterized by peripheral nerve problems, deafness, and vision loss.  https://ghr.nlm.nih.gov/condition/charcot-marie-tooth-disease

Clinical features

Pes cavus
MedGen UID:
675590
Concept ID:
C0728829
Congenital Abnormality
The presence of an unusually high plantar arch. Also called high instep, pes cavus refers to a distinctly hollow form of the sole of the foot when it is bearing weight.
Hammertoe
MedGen UID:
209712
Concept ID:
C1136179
Anatomical Abnormality
Hyperextension of the metatarsal-phalangeal joint with hyperflexion of the proximal interphalangeal (PIP) joint.
Upper limb muscle weakness
MedGen UID:
305607
Concept ID:
C1698196
Finding
Weakness of the muscles of the arms.
Upper limb amyotrophy
MedGen UID:
867165
Concept ID:
C4021523
Disease or Syndrome
Muscular atrophy involving the muscles of the upper limbs.
Upper limb muscle weakness
MedGen UID:
305607
Concept ID:
C1698196
Finding
Weakness of the muscles of the arms.
Cold-induced hand cramps
MedGen UID:
330428
Concept ID:
C1832279
Finding
Upper limb amyotrophy
MedGen UID:
867165
Concept ID:
C4021523
Disease or Syndrome
Muscular atrophy involving the muscles of the upper limbs.
Hammertoe
MedGen UID:
209712
Concept ID:
C1136179
Anatomical Abnormality
Hyperextension of the metatarsal-phalangeal joint with hyperflexion of the proximal interphalangeal (PIP) joint.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
Follow this link to review classifications for Charcot-Marie-Tooth disease type 2D in Orphanet.

Recent clinical studies

Etiology

Liao YC, Liu YT, Tsai PC, Chang CC, Huang YH, Soong BW, Lee YC
PLoS One 2015;10(8):e0133423. Epub 2015 Aug 5 doi: 10.1371/journal.pone.0133423. PMID: 26244500Free PMC Article
Sun A, Liu X, Zheng M, Sun Q, Huang Y, Fan D
Neurol Res 2015 Sep;37(9):782-7. Epub 2015 May 22 doi: 10.1179/1743132815Y.0000000055. PMID: 26000875
Gardiner J, Marc J
J Exp Bot 2011 Jan;62(1):89-97. Epub 2010 Sep 2 doi: 10.1093/jxb/erq278. PMID: 20813785

Diagnosis

Liao YC, Liu YT, Tsai PC, Chang CC, Huang YH, Soong BW, Lee YC
PLoS One 2015;10(8):e0133423. Epub 2015 Aug 5 doi: 10.1371/journal.pone.0133423. PMID: 26244500Free PMC Article

Clinical prediction guides

Motley WW, Seburn KL, Nawaz MH, Miers KE, Cheng J, Antonellis A, Green ED, Talbot K, Yang XL, Fischbeck KH, Burgess RW
PLoS Genet 2011 Dec;7(12):e1002399. Epub 2011 Dec 1 doi: 10.1371/journal.pgen.1002399. PMID: 22144914Free PMC Article
Sambuughin N, Sivakumar K, Selenge B, Lee HS, Friedlich D, Baasanjav D, Dalakas MC, Goldfarb LG
J Neurol Sci 1998 Nov 26;161(1):23-8. PMID: 9879677

Supplemental Content

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...
Support Center