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Charcot-Marie-Tooth disease type 2B(CMT2B)

MedGen UID:
371512
Concept ID:
C1833219
Disease or Syndrome
Synonyms: CHARCOT-MARIE-TOOTH DISEASE, AUTOSOMAL DOMINANT, TYPE 2B; Charcot-Marie-Tooth disease, axonal, type 2b; Charcot-Marie-Tooth disease, neuronal, Type 2B; Charcot-Marie-Tooth Neuropathy Type 2B; CMT 2B; CMT2B; Hereditary motor and sensory neuropathy 2 B (HMSN 2 B); HEREDITARY MOTOR AND SENSORY NEUROPATHY IIB; Peripheral sensory neuropathy, autosomal dominant (PSN)
SNOMED CT: Autosomal dominant Charcot-Marie-Tooth disease type 2B (717008005)
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Gene (location): RAB7A (3q21.3)
 
Monarch Initiative: MONDO:0010949
OMIM®: 600882
Orphanet: ORPHA99936

Definition

A severe form of axonal Charcot-Marie-Tooth disease, a peripheral sensorimotor neuropathy. Onset in the second or third decade has manifestations of ulceration and infection of the feet. Symmetric and distal weakness develops mostly in the legs together with a severe symmetric distal sensory loss. Tendon reflexes are only reduced at ankles and foot deformities including pes cavus or planus and hammer toes, appear in childhood. [from SNOMEDCT_US]

Clinical features

From HPO
Pes planus
MedGen UID:
42034
Concept ID:
C0016202
Anatomical Abnormality
A foot where the longitudinal arch of the foot is in contact with the ground or floor when the individual is standing; or, in a patient lying supine, a foot where the arch is in contact with the surface of a flat board pressed against the sole of the foot by the examiner with a pressure similar to that expected from weight bearing; or, the height of the arch is reduced.
Absent Achilles reflex
MedGen UID:
108240
Concept ID:
C0558845
Finding
Absence of the Achilles reflex (also known as the ankle jerk reflex), which can normally be elicited by tapping the tendon is tapped while the foot is dorsiflexed.
Pes cavus
MedGen UID:
675590
Concept ID:
C0728829
Congenital Abnormality
An increase in height of the medial longitudinal arch of the foot that does not flatten on weight bearing (i.e., 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.
Autoamputation
MedGen UID:
331463
Concept ID:
C1833222
Finding
Auto-amputation is the spontaneous detachment of an appendage from the body due to long standing pathology.
Distal lower limb muscle weakness
MedGen UID:
324514
Concept ID:
C1836450
Finding
Reduced strength of the distal musculature of the legs.
Foot dorsiflexor weakness
MedGen UID:
356163
Concept ID:
C1866141
Finding
Weakness of the muscles responsible for dorsiflexion of the foot, that is, of the movement of the toes towards the shin. The foot dorsiflexors include the tibialis anterior, the extensor hallucis longus, the extensor digitorum longus, and the peroneus tertius muscles.
Autoamputation of foot
MedGen UID:
871255
Concept ID:
C4025740
Finding
The spontaneous detachment of a foot from the body due to long standing pathology.
Fasciculations
MedGen UID:
5124
Concept ID:
C0015644
Sign or Symptom
Fasciculations are observed as small, local, involuntary muscle contractions (twitching) visible under the skin. Fasciculations result from increased irritability of an axon (which in turn is often a manifestation of disease of a motor neuron). This leads to sporadic discharges of all the muscle fibers controlled by the axon in isolation from other motor units.
Peripheral neuropathy
MedGen UID:
18386
Concept ID:
C0031117
Disease or Syndrome
Peripheral neuropathy is a general term for any disorder of the peripheral nervous system. The main clinical features used to classify peripheral neuropathy are distribution, type (mainly demyelinating versus mainly axonal), duration, and course.
Sensory neuropathy
MedGen UID:
101791
Concept ID:
C0151313
Disease or Syndrome
Peripheral neuropathy affecting the sensory nerves.
Areflexia
MedGen UID:
115943
Concept ID:
C0234146
Finding
Absence of neurologic reflexes such as the knee-jerk reaction.
Steppage gait
MedGen UID:
98105
Concept ID:
C0427149
Finding
An abnormal gait pattern that arises from weakness of the pretibial and peroneal muscles due to a lower motor neuron lesion. Affected patients have footdrop and are unable to dorsiflex and evert the foot. The leg is lifted high on walking so that the toes clear the ground, and there may be a slapping noise when the foot strikes the ground again.
Hyporeflexia
MedGen UID:
195967
Concept ID:
C0700078
Finding
Reduction of neurologic reflexes such as the knee-jerk reaction.
Sensorimotor neuropathy
MedGen UID:
207266
Concept ID:
C1112256
Disease or Syndrome
Decreased number of peripheral myelinated nerve fibers
MedGen UID:
346872
Concept ID:
C1858285
Finding
A loss of myelinated nerve fibers in the peripheral nervous system (in general, this finding can be observed on nerve biopsy).
Decreased motor nerve conduction velocity
MedGen UID:
388130
Concept ID:
C1858729
Finding
A type of decreased nerve conduction velocity that affects the motor neuron.
Axonal degeneration/regeneration
MedGen UID:
368889
Concept ID:
C1968790
Finding
A pattern of simultaneous degeneration and regeneration of axons (see comment).
Impaired distal tactile sensation
MedGen UID:
867225
Concept ID:
C4021583
Finding
A reduced sense of touch (tactile sensation) on the skin of the distal limbs. This is usually tested with a wisp of cotton or a fine camel's hair brush, by asking patients to say 'now' each time they feel the stimulus.
Peripheral axonal atrophy
MedGen UID:
871146
Concept ID:
C4025619
Disease or Syndrome
Atrophic changes of axons of the peripheral nervous system.
Decreased compound muscle action potential amplitude
MedGen UID:
908357
Concept ID:
C4230625
Finding
Reduced level of the compound muscle action potential (CMAP), which is recorded following electrical stimulation of a nerve from surface electrodes overlying a muscle supplied by that nerve.
Somatic sensory dysfunction
MedGen UID:
1790456
Concept ID:
C5551413
Finding
An abnormality of the primary sensation that is mediated by peripheral nerves (pain, temperature, touch, vibration, joint position). The word hypoesthesia (or hypesthesia) refers to a reduction in cutaneous sensation to a specific type of testing.
Distal muscle weakness
MedGen UID:
140883
Concept ID:
C0427065
Finding
Reduced strength of the musculature of the distal extremities.
Distal lower limb amyotrophy
MedGen UID:
324515
Concept ID:
C1836451
Disease or Syndrome
Muscular atrophy of distal leg muscles.
Distal amyotrophy
MedGen UID:
338530
Concept ID:
C1848736
Disease or Syndrome
Muscular atrophy affecting muscles in the distal portions of the extremities.
Foot osteomyelitis
MedGen UID:
1370023
Concept ID:
C4049342
Disease or Syndrome
An infection of bone of the foot.
Dystrophic toenail
MedGen UID:
318813
Concept ID:
C1833225
Finding
Toenail changes apart from changes of the color of the toenail (nail dyschromia) that involve partial or complete disruption of the various keratinous layers of the nail plate.

Term Hierarchy

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

Recent clinical studies

Diagnosis

Manganelli F, Pisciotta C, Provitera V, Taioli F, Iodice R, Topa A, Fabrizi GM, Nolano M, Santoro L
J Peripher Nerv Syst 2012 Sep;17(3):361-4. doi: 10.1111/j.1529-8027.2012.00415.x. PMID: 22971099

Prognosis

Saveri P, De Luca M, Nisi V, Pisciotta C, Romano R, Piscosquito G, Reilly MM, Polke JM, Cavallaro T, Fabrizi GM, Fossa P, Cichero E, Lombardi R, Lauria G, Magri S, Taroni F, Pareyson D, Bucci C
Cells 2020 Apr 21;9(4) doi: 10.3390/cells9041028. PMID: 32326241Free PMC Article
Nicolaou P, Cianchetti C, Minaidou A, Marrosu G, Zamba-Papanicolaou E, Middleton L, Christodoulou K
Eur J Hum Genet 2013 Feb;21(2):190-4. Epub 2012 Jul 11 doi: 10.1038/ejhg.2012.146. PMID: 22781092Free PMC Article
Fischer D, Herasse M, Bitoun M, Barragán-Campos HM, Chiras J, Laforêt P, Fardeau M, Eymard B, Guicheney P, Romero NB
Brain 2006 Jun;129(Pt 6):1463-9. Epub 2006 Apr 3 doi: 10.1093/brain/awl071. PMID: 16585051

Clinical prediction guides

Romano R, Rivellini C, De Luca M, Tonlorenzi R, Beli R, Manganelli F, Nolano M, Santoro L, Eskelinen EL, Previtali SC, Bucci C
Cell Mol Life Sci 2021 Jan;78(1):351-372. Epub 2020 Apr 13 doi: 10.1007/s00018-020-03510-1. PMID: 32280996Free PMC Article
Giudetti AM, Guerra F, Longo S, Beli R, Romano R, Manganelli F, Nolano M, Mangini V, Santoro L, Bucci C
Biochim Biophys Acta Mol Cell Biol Lipids 2020 Dec;1865(12):158805. Epub 2020 Aug 21 doi: 10.1016/j.bbalip.2020.158805. PMID: 32829064
Saveri P, De Luca M, Nisi V, Pisciotta C, Romano R, Piscosquito G, Reilly MM, Polke JM, Cavallaro T, Fabrizi GM, Fossa P, Cichero E, Lombardi R, Lauria G, Magri S, Taroni F, Pareyson D, Bucci C
Cells 2020 Apr 21;9(4) doi: 10.3390/cells9041028. PMID: 32326241Free PMC Article
Colecchia D, Stasi M, Leonardi M, Manganelli F, Nolano M, Veneziani BM, Santoro L, Eskelinen EL, Chiariello M, Bucci C
Autophagy 2018;14(6):930-941. Epub 2018 May 4 doi: 10.1080/15548627.2017.1388475. PMID: 29130394Free PMC Article
Liu H, Wu C
Int J Mol Sci 2017 Feb 4;18(2) doi: 10.3390/ijms18020324. PMID: 28165391Free PMC Article

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