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Charcot-Marie-Tooth disease axonal type 2P(CMT2P; CMT2G, FORMERLY)

MedGen UID:
482427
Concept ID:
C3280797
Disease or Syndrome
Synonyms: Charcot-Marie-Tooth disease type 2P; CHARCOT-MARIE-TOOTH DISEASE, AXONAL, TYPE 2G; Charcot-Marie-Tooth Neuropathy Type 2G; CHARCOT-MARIE-TOOTH NEUROPATHY, TYPE 2P; CMT 2G
SNOMED CT: Charcot-Marie-Tooth disease type 2P (782826009); CMT2P - Charcot-Marie-Tooth disease type 2P (782826009)
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): LRSAM1 (9q33.3-34.11)
 
Monarch Initiative: MONDO:0013753
OMIM®: 614436
Orphanet: ORPHA99941

Definition

A rare genetic axonal hereditary motor and sensory neuropathy disorder with characteristics of adulthood-onset of slowly progressive, occasionally asymmetrical, distal muscle weakness and atrophy (predominantly in the lower limbs), pan-modal sensory loss, muscle cramping in extremities and/or trunk, pes cavus and absent or reduced deep tendon reflexes. Gait anomalies and variable autonomic disturbances, such as erectile dysfunction and urinary urgency, may be associated. The disease can be caused by homozygous or heterozygous mutation in the LRSAM1 gene on chromosome 9q33. [from SNOMEDCT_US]

Clinical features

From HPO
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.
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.
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.
Areflexia
MedGen UID:
115943
Concept ID:
C0234146
Finding
Absence of neurologic reflexes such as the knee-jerk reaction.
Tip-toe gait
MedGen UID:
98104
Concept ID:
C0427144
Finding
An abnormal gait pattern characterized by the failure of the heel to contact the floor at the onset of stance during gait.
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.
Axonal degeneration
MedGen UID:
332464
Concept ID:
C1837496
Finding
Distal sensory impairment
MedGen UID:
335722
Concept ID:
C1847584
Finding
An abnormal reduction in sensation in the distal portions of the extremities.
Impaired distal vibration sensation
MedGen UID:
381262
Concept ID:
C1853767
Finding
A decrease in the ability to perceive vibration in the distal portions of the limbs.
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).
Peripheral axonal degeneration
MedGen UID:
871339
Concept ID:
C4025830
Finding
Progressive deterioration of peripheral axons.
Distal muscle weakness
MedGen UID:
140883
Concept ID:
C0427065
Finding
Reduced strength of the musculature of the distal extremities.
Distal amyotrophy
MedGen UID:
338530
Concept ID:
C1848736
Disease or Syndrome
Muscular atrophy affecting muscles in the distal portions of the extremities.

Term Hierarchy

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

Recent clinical studies

Etiology

Hakonen JE, Sorrentino V, Avagliano Trezza R, de Wissel MB, van den Berg M, Bleijlevens B, van Ruissen F, Distel B, Baas F, Zelcer N, Weterman MAJ
Hum Mol Genet 2017 Jun 1;26(11):2034-2041. doi: 10.1093/hmg/ddx089. PMID: 28335037
Hu B, Arpag S, Zuchner S, Li J
Ann Neurol 2016 Dec;80(6):834-845. Epub 2016 Sep 27 doi: 10.1002/ana.24776. PMID: 27615052Free PMC Article

Diagnosis

Palaima P, Berciano J, Peeters K, Jordanova A
Orphanet J Rare Dis 2021 Feb 10;16(1):74. doi: 10.1186/s13023-020-01654-8. PMID: 33568173Free PMC Article

Clinical prediction guides

Mishra R, Amanullah A, Upadhyay A, Dhiman R, Dubey AR, Singh S, Prasad A, Mishra A
Int J Biochem Cell Biol 2020 Mar;120:105697. Epub 2020 Jan 23 doi: 10.1016/j.biocel.2020.105697. PMID: 31982566