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Charcot-Marie-Tooth disease X-linked recessive 2(CMTX2)

MedGen UID:
336803
Concept ID:
C1844873
Disease or Syndrome
Synonyms: Charcot-Marie-Tooth Neuropathy X Type 2; CHARCOT-MARIE-TOOTH NEUROPATHY, X-LINKED RECESSIVE, 2; CMTX 2
SNOMED CT: X-linked Charcot-Marie-Tooth disease type 2 (763457000)
Modes of inheritance:
X-linked recessive inheritance
MedGen UID:
375779
Concept ID:
C1845977
Finding
Source: Orphanet
A mode of inheritance that is observed for recessive traits related to a gene encoded on the X chromosome. In the context of medical genetics, X-linked recessive disorders manifest in males (who have one copy of the X chromosome and are thus hemizygotes), but generally not in female heterozygotes who have one mutant and one normal allele.
 
Monarch Initiative: MONDO:0010550
OMIM®: 302801
Orphanet: ORPHA101076

Definition

A rare genetic peripheral sensorimotor neuropathy with an X-linked recessive inheritance pattern and the infantile to childhood-onset of progressive, distal muscle weakness and atrophy (more prominent in the lower extremities than in the upper extremities), pes cavus, and absent tendon reflexes. Sensory impairment and intellectual disability has been reported in some individuals. [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).
Upper limb muscle weakness
MedGen UID:
305607
Concept ID:
C1698196
Finding
Weakness of the muscles of the arms.
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.
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.
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.
Distal sensory impairment
MedGen UID:
335722
Concept ID:
C1847584
Finding
An abnormal reduction in sensation in the distal portions of the extremities.
Decreased motor nerve conduction velocity
MedGen UID:
388130
Concept ID:
C1858729
Finding
A type of decreased nerve conduction velocity that affects the motor neuron.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
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.
EMG: axonal abnormality
MedGen UID:
871138
Concept ID:
C4025609
Pathologic Function
Electromyographic (EMG) findings characteristic of axonal neuropathy, with normal or slightly decreased nerve conduction velocities, normal or slightly prolonged distal latencies, but significantly reduced motor potentials and sensory amplitudes. There may be spontaneous activity upon needle EMG studies, such as increased insertional activity, positive sharp waves, and fibrillation potentials.

Term Hierarchy

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

Professional guidelines

PubMed

Nicholson G, Kennerson M, Brewer M, Garbern J, Shy M
Adv Exp Med Biol 2009;652:201-6. doi: 10.1007/978-90-481-2813-6_13. PMID: 20225027
Chance PF
Suppl Clin Neurophysiol 2004;57:228-42. doi: 10.1016/s1567-424x(09)70360-5. PMID: 16106622

Recent clinical studies

Etiology

Zambon AA, Pini V, Bosco L, Falzone YM, Munot P, Muntoni F, Previtali SC
Brain 2023 Mar 1;146(3):806-822. doi: 10.1093/brain/awac452. PMID: 36445400Free PMC Article
Ashrafi MR, Amanat M, Garshasbi M, Kameli R, Nilipour Y, Heidari M, Rezaei Z, Tavasoli AR
Expert Rev Neurother 2020 Jan;20(1):65-84. Epub 2019 Dec 12 doi: 10.1080/14737175.2020.1699060. PMID: 31829048
Kanhangad M, Cornett K, Brewer MH, Nicholson GA, Ryan MM, Smith RL, Subramanian GM, Young HK, Züchner S, Kennerson ML, Burns J, Menezes MP
Neurology 2018 May 8;90(19):e1706-e1710. Epub 2018 Apr 6 doi: 10.1212/WNL.0000000000005479. PMID: 29626178Free PMC Article
Azzedine H, Ravisé N, Verny C, Gabrëels-Festen A, Lammens M, Grid D, Vallat JM, Durosier G, Senderek J, Nouioua S, Hamadouche T, Bouhouche A, Guilbot A, Stendel C, Ruberg M, Brice A, Birouk N, Dubourg O, Tazir M, LeGuern E
Neurology 2006 Aug 22;67(4):602-6. doi: 10.1212/01.wnl.0000230225.19797.93. PMID: 16924012
Houlden H, Reilly MM
Neuromolecular Med 2006;8(1-2):43-62. doi: 10.1385/nmm:8:1-2:43. PMID: 16775366

Diagnosis

Zambon AA, Pini V, Bosco L, Falzone YM, Munot P, Muntoni F, Previtali SC
Brain 2023 Mar 1;146(3):806-822. doi: 10.1093/brain/awac452. PMID: 36445400Free PMC Article
Ashrafi MR, Amanat M, Garshasbi M, Kameli R, Nilipour Y, Heidari M, Rezaei Z, Tavasoli AR
Expert Rev Neurother 2020 Jan;20(1):65-84. Epub 2019 Dec 12 doi: 10.1080/14737175.2020.1699060. PMID: 31829048
Kaler SG
Handb Clin Neurol 2013;113:1745-54. doi: 10.1016/B978-0-444-59565-2.00045-9. PMID: 23622398Free PMC Article
Ouvrier R, Geevasingha N, Ryan MM
Muscle Nerve 2007 Aug;36(2):131-43. doi: 10.1002/mus.20776. PMID: 17410579
Vallat JM
J Neuropathol Exp Neurol 2003 Jul;62(7):699-714. doi: 10.1093/jnen/62.7.699. PMID: 12901697

Therapy

Kaler SG
Handb Clin Neurol 2013;113:1745-54. doi: 10.1016/B978-0-444-59565-2.00045-9. PMID: 23622398Free PMC Article

Prognosis

Kaler SG
Handb Clin Neurol 2013;113:1745-54. doi: 10.1016/B978-0-444-59565-2.00045-9. PMID: 23622398Free PMC Article
Azzedine H, Ravisé N, Verny C, Gabrëels-Festen A, Lammens M, Grid D, Vallat JM, Durosier G, Senderek J, Nouioua S, Hamadouche T, Bouhouche A, Guilbot A, Stendel C, Ruberg M, Brice A, Birouk N, Dubourg O, Tazir M, LeGuern E
Neurology 2006 Aug 22;67(4):602-6. doi: 10.1212/01.wnl.0000230225.19797.93. PMID: 16924012

Clinical prediction guides

Kanhangad M, Cornett K, Brewer MH, Nicholson GA, Ryan MM, Smith RL, Subramanian GM, Young HK, Züchner S, Kennerson ML, Burns J, Menezes MP
Neurology 2018 May 8;90(19):e1706-e1710. Epub 2018 Apr 6 doi: 10.1212/WNL.0000000000005479. PMID: 29626178Free PMC Article
Ouvrier R, Geevasingha N, Ryan MM
Muscle Nerve 2007 Aug;36(2):131-43. doi: 10.1002/mus.20776. PMID: 17410579
Azzedine H, Ravisé N, Verny C, Gabrëels-Festen A, Lammens M, Grid D, Vallat JM, Durosier G, Senderek J, Nouioua S, Hamadouche T, Bouhouche A, Guilbot A, Stendel C, Ruberg M, Brice A, Birouk N, Dubourg O, Tazir M, LeGuern E
Neurology 2006 Aug 22;67(4):602-6. doi: 10.1212/01.wnl.0000230225.19797.93. PMID: 16924012
Ionasescu VV, Trofatter J, Haines JL, Summers AM, Ionasescu R, Searby C
Muscle Nerve 1992 Mar;15(3):368-73. doi: 10.1002/mus.880150317. PMID: 1557086
Ionasescu VV, Trofatter J, Haines JL, Summers AM, Ionasescu R, Searby C
Am J Hum Genet 1991 Jun;48(6):1075-83. PMID: 1674639Free PMC Article

Recent systematic reviews

Berciano J, García A, Gallardo E, Peeters K, Pelayo-Negro AL, Álvarez-Paradelo S, Gazulla J, Martínez-Tames M, Infante J, Jordanova A
J Neurol 2017 Aug;264(8):1655-1677. Epub 2017 Mar 31 doi: 10.1007/s00415-017-8474-3. PMID: 28364294

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