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Charcot-Marie-Tooth disease type 4B2(CMT4B2)

MedGen UID:
346869
Concept ID:
C1858278
Disease or Syndrome
Synonyms: CHARCOT-MARIE-TOOTH DISEASE, DEMYELINATING, TYPE 4B2; CHARCOT-MARIE-TOOTH DISEASE, WITH FOCALLY FOLDED MYELIN SHEATHS, AUTOSOMAL RECESSIVE, TYPE 4B2; Charcot-Marie-Tooth Neuropathy Type 4B2; Charcot-Marie-Tooth Neuropathy Type 4B2 (CMT4B2); CMT 4B2
SNOMED CT: Charcot-Marie-Tooth disease type 4B2 (715800000)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
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 individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): SBF2 (11p15.4)
 
Monarch Initiative: MONDO:0011475
OMIM®: 604563
Orphanet: ORPHA99956

Definition

Autosomal recessive Charcot-Marie-Tooth disease type 4B2 (CMT4B2) is a demyelinating hereditary motor and sensory neuropathy characterized by abnormal folding of myelin sheaths. CMT4B1 (601382) is a clinically similar disorder caused by mutation in the MTMR2 gene (603557) on 11q22. For a phenotypic description and a discussion of genetic heterogeneity of autosomal recessive demyelinating CMT, see CMT4A (214400). [from OMIM]

Clinical features

From HPO
Clubfoot
MedGen UID:
3130
Concept ID:
C0009081
Congenital Abnormality
Clubfoot is a congenital limb deformity defined as fixation of the foot in cavus, adductus, varus, and equinus (i.e., inclined inwards, axially rotated outwards, and pointing downwards) with concomitant soft tissue abnormalities (Cardy et al., 2007). Clubfoot may occur in isolation or as part of a syndrome (e.g., diastrophic dysplasia, 222600). Clubfoot has been reported with deficiency of long bones and mirror-image polydactyly (Gurnett et al., 2008; Klopocki et al., 2012).
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.
Split hand
MedGen UID:
397570
Concept ID:
C2699510
Congenital Abnormality
A condition in which middle parts of the hand (fingers and metacarpals) are missing giving a cleft appearance. The severity is very variable ranging from slightly hypoplastic middle fingers over absent middle fingers as far as oligo- or monodactyl hands.
Ulnar claw
MedGen UID:
871311
Concept ID:
C4025799
Congenital Abnormality
An abnormal hand position characterized by hyperextension of the fourth and fifth fingers at the metacarpophalangeal joints and flexion of the interphalangeal joints of the same fingers such that they are curled towards the palm.
Sensorineural hearing loss disorder
MedGen UID:
9164
Concept ID:
C0018784
Disease or Syndrome
A type of hearing impairment in one or both ears related to an abnormal functionality of the cochlear nerve.
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.
Gait disturbance
MedGen UID:
107895
Concept ID:
C0575081
Finding
The term gait disturbance can refer to any disruption of the ability to walk.
Hyporeflexia
MedGen UID:
195967
Concept ID:
C0700078
Finding
Reduction of neurologic reflexes such as the knee-jerk reaction.
Segmental peripheral demyelination/remyelination
MedGen UID:
335873
Concept ID:
C1843077
Finding
A segmental pattern of demyelination and regeneration (remyelination) affecting peripheral nerves.
Distal sensory impairment
MedGen UID:
335722
Concept ID:
C1847584
Finding
An abnormal reduction in sensation in the distal portions of the extremities.
Onion bulb formation
MedGen UID:
376237
Concept ID:
C1847906
Finding
Repeated episodes of segmental demyelination and remyelination lead to the accumulation of supernumerary Schwann cells around axons, which is referred to as onion bulb formation. This finding affects peripheral nerves.
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.
Distal muscle weakness
MedGen UID:
140883
Concept ID:
C0427065
Finding
Reduced strength of the musculature of the distal extremities.
Kyphoscoliosis
MedGen UID:
154361
Concept ID:
C0575158
Anatomical Abnormality
An abnormal curvature of the spine in both a coronal (lateral) and sagittal (back-to-front) plane.
Distal amyotrophy
MedGen UID:
338530
Concept ID:
C1848736
Disease or Syndrome
Muscular atrophy affecting muscles in the distal portions of the extremities.
Glaucoma
MedGen UID:
42224
Concept ID:
C0017601
Disease or Syndrome
Glaucoma refers loss of retinal ganglion cells in a characteristic pattern of optic neuropathy usually associated with increased intraocular pressure.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
Follow this link to review classifications for Charcot-Marie-Tooth disease type 4B2 in Orphanet.

Recent clinical studies

Etiology

Sawade L, Grandi F, Mignanelli M, Patiño-López G, Klinkert K, Langa-Vives F, Di Guardo R, Echard A, Bolino A, Haucke V
Nat Commun 2020 Jun 5;11(1):2835. doi: 10.1038/s41467-020-16696-6. PMID: 32503983Free PMC Article
Pareyson D, Stojkovic T, Reilly MM, Leonard-Louis S, Laurà M, Blake J, Parman Y, Battaloglu E, Tazir M, Bellatache M, Bonello-Palot N, Lévy N, Sacconi S, Guimarães-Costa R, Attarian S, Latour P, Solé G, Megarbane A, Horvath R, Ricci G, Choi BO, Schenone A, Gemelli C, Geroldi A, Sabatelli M, Luigetti M, Santoro L, Manganelli F, Quattrone A, Valentino P, Murakami T, Scherer SS, Dankwa L, Shy ME, Bacon CJ, Herrmann DN, Zambon A, Tramacere I, Pisciotta C, Magri S, Previtali SC, Bolino A
Ann Neurol 2019 Jul;86(1):55-67. Epub 2019 May 27 doi: 10.1002/ana.25500. PMID: 31070812Free PMC Article

Diagnosis

Pareyson D, Stojkovic T, Reilly MM, Leonard-Louis S, Laurà M, Blake J, Parman Y, Battaloglu E, Tazir M, Bellatache M, Bonello-Palot N, Lévy N, Sacconi S, Guimarães-Costa R, Attarian S, Latour P, Solé G, Megarbane A, Horvath R, Ricci G, Choi BO, Schenone A, Gemelli C, Geroldi A, Sabatelli M, Luigetti M, Santoro L, Manganelli F, Quattrone A, Valentino P, Murakami T, Scherer SS, Dankwa L, Shy ME, Bacon CJ, Herrmann DN, Zambon A, Tramacere I, Pisciotta C, Magri S, Previtali SC, Bolino A
Ann Neurol 2019 Jul;86(1):55-67. Epub 2019 May 27 doi: 10.1002/ana.25500. PMID: 31070812Free PMC Article
Laššuthová P, Vill K, Erdem-Ozdamar S, Schröder JM, Topaloglu H, Horvath R, Müller-Felber W, Bansagi B, Schlotter-Weigel B, Gläser D, Neupauerová J, Sedláčková L, Staněk D, Mazanec R, Weis J, Seeman P, Senderek J
Clin Genet 2018 Nov;94(5):467-472. Epub 2018 Aug 14 doi: 10.1111/cge.13417. PMID: 30028002
Negrão L, Almendra L, Ribeiro J, Matos A, Geraldo A, Pinto-Basto J
Acta Myol 2014 Dec;33(3):144-8. PMID: 25873783Free PMC Article
Chen M, Wu J, Liang N, Tang L, Chen Y, Chen H, Wei W, Wei T, Huang H, Yi X, Qi M
Genomics Proteomics Bioinformatics 2014 Oct;12(5):221-7. Epub 2014 Oct 28 doi: 10.1016/j.gpb.2014.09.003. PMID: 25462154Free PMC Article

Prognosis

Pareyson D, Stojkovic T, Reilly MM, Leonard-Louis S, Laurà M, Blake J, Parman Y, Battaloglu E, Tazir M, Bellatache M, Bonello-Palot N, Lévy N, Sacconi S, Guimarães-Costa R, Attarian S, Latour P, Solé G, Megarbane A, Horvath R, Ricci G, Choi BO, Schenone A, Gemelli C, Geroldi A, Sabatelli M, Luigetti M, Santoro L, Manganelli F, Quattrone A, Valentino P, Murakami T, Scherer SS, Dankwa L, Shy ME, Bacon CJ, Herrmann DN, Zambon A, Tramacere I, Pisciotta C, Magri S, Previtali SC, Bolino A
Ann Neurol 2019 Jul;86(1):55-67. Epub 2019 May 27 doi: 10.1002/ana.25500. PMID: 31070812Free PMC Article
Robinson DC, Mammel AE, Logan AM, Larson AA, Schmidt EJ, Condon AF, Robinson FL
ASN Neuro 2018 Jan-Dec;10:1759091418803282. doi: 10.1177/1759091418803282. PMID: 30419760Free PMC Article
Laššuthová P, Vill K, Erdem-Ozdamar S, Schröder JM, Topaloglu H, Horvath R, Müller-Felber W, Bansagi B, Schlotter-Weigel B, Gläser D, Neupauerová J, Sedláčková L, Staněk D, Mazanec R, Weis J, Seeman P, Senderek J
Clin Genet 2018 Nov;94(5):467-472. Epub 2018 Aug 14 doi: 10.1111/cge.13417. PMID: 30028002

Clinical prediction guides

Pareyson D, Stojkovic T, Reilly MM, Leonard-Louis S, Laurà M, Blake J, Parman Y, Battaloglu E, Tazir M, Bellatache M, Bonello-Palot N, Lévy N, Sacconi S, Guimarães-Costa R, Attarian S, Latour P, Solé G, Megarbane A, Horvath R, Ricci G, Choi BO, Schenone A, Gemelli C, Geroldi A, Sabatelli M, Luigetti M, Santoro L, Manganelli F, Quattrone A, Valentino P, Murakami T, Scherer SS, Dankwa L, Shy ME, Bacon CJ, Herrmann DN, Zambon A, Tramacere I, Pisciotta C, Magri S, Previtali SC, Bolino A
Ann Neurol 2019 Jul;86(1):55-67. Epub 2019 May 27 doi: 10.1002/ana.25500. PMID: 31070812Free PMC Article
Robinson DC, Mammel AE, Logan AM, Larson AA, Schmidt EJ, Condon AF, Robinson FL
ASN Neuro 2018 Jan-Dec;10:1759091418803282. doi: 10.1177/1759091418803282. PMID: 30419760Free PMC Article

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