Charcot-Marie-Tooth Disease, Type 4B2

Alternative Names

CMT4B2
Charcot-Marie-Tooth Disease, with Focally Folded Myelin Sheaths, Autosomal Recessive, Type 4B2
Charcot-Marie-Tooth Neuropathy, Type 4B2
Charcot-Marie-Tooth Disease, Type 4B2, with Early-Onset Glaucoma
Charcot-Marie-Tooth Neuropathy, Type 4B2, with Early-Onset Glaucoma

Associated Genes

SET-Binding Factor 2

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WHO-ICD-10 version:2010

Diseases of the nervous system

Polyneuropathies and other disorders of the peripheral nervous system

OMIM Number

604563

Mode of Inheritance

Autosomal recessive

Gene Map Locus

11p15

Description

Charcot-Marie-Tooth disease type 4 (CMT4) is a group of progressive neurological disorders affecting the motor and sensory axons and results in demyelination. Myelin is the substance that covers nerve cells and provides protection for these cells. Also, myelin promotes the rapid transmission of nerve impulses. CMT4B is characterized by abnormal folding of myelin sheaths. Individuals with CMT4B2 may also present with a buildup of pressure within the eye and degeneration of optic nerve (glaucoma). The subgroups of CMT4 are inherited as an autosomal recessive trait. Autosomal recessive inheritance allows the differentiation of CMT4 from the other forms of CMT. Patients with CMT4 have distal muscle weakness and atrophy associated with sensory loss and, frequently, pes cavus foot deformity. Males are often affected more than females which can be attributed to the increased possibility of nerve trauma.

Molecular Genetics

Charcot-Marie-Tooth disease type 4 (CMT4) is caused by mutations in the SET-binding factor 2 (SBF2) gene. SBF2 gene is also known as the myotubularin-related 13 (MTMR13) gene. This gene encodes the SBF2 protein which is thought to play a role in cellular communication or the signaling network that is essential for the production of myelin. It is also suggested that SBF2 protein has a role in the development of trabecular meshwork that surround the iris in the eyes. Mutations in the SBF2 gene alter the structure of the produced protein and result in a loss of the protein's function. Thus, myelin will have irregular structure (out-folded) which is a specific sign of type 4B2 Charcot-Marie-Tooth disease. Glaucoma occurs, if mutations in SBF2 gene cause complete loss of protein function. On the other hand, partial loss of protein function will not cause glaucoma.

Epidemiology in the Arab World

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Other Reports

Morocco

Azzedine et al. (2003) described three patients with demyelinating Charcot-Marie-Tooth disease (CTM) and early-onset glaucoma. Those patients were two females and one male from a large consanguineous Moroccan family. The parents and one other male sibs were examined clinically and electrophysiologically and they were normal. The mean age at the onset of sensory motor neuropathy was eight years. A distal motor deficit was affecting the four limbs and motor nerve velocities were highly reduced (<20 m/s). Sensory nerve action potentials were altered. Nerve biopsy revealed myelin out-folding. The index patient had a vision loss and ophthalmologic examination displayed clear signs of congenital glaucoma with a buphthalmos, a megalocornea, and raised intraocular pressure. Other affected members had increasing intraocular pressure.

Tunisia

In 2 Tunisian families with a CMT4B phenotype, Ben Othmane et al. (1999) excluded linkage to the CMT4B1 locus, thus demonstrating genetic heterogeneity. Using homozygosity mapping and linkage analysis in the largest Tunisian pedigree, they mapped the disorder to chromosome 11p15. A maximum 2-point lod score of 6.05 was obtained with marker D11S1329. Recombination events refined the CMT4B2 locus region to a 5.6-cM interval between markers D11S1331 and D11S4194. The second Tunisian CMT4B family was also excluded from linkage to the 11p15 locus, demonstrating the existence of at least a third locus for the CMT4B phenotype.

Azzedine et al. (2003) identified four female patients with demyelinating Charcot-Marie-Tooth disease (CTM) and early-onset glaucoma. Those patients were related to a large consanguineous Tunisian family. All other family members were examined clinically and electrophysiologically, including the apparently normal parents. The mean age at the onset of sensory motor neuropathy was eight years. A distal motor deficit was affecting the four limbs and motor nerve velocities were highly reduced (<20 m/s). Sensory nerve action potentials were altered. Nerve biopsy revealed myelin out-folding. The index patient had a vision loss and ophthalmologic examination displayed clear signs of congenital glaucoma with a buphthalmos, a megalocornea, and raised intraocular pressure. Other affected members had increasing intraocular pressure.

External Links

http://ghr.nlm.nih.gov/gene=sbf2 http://www.genetests.org/profiles/cmt4 http://www.telethon.it/dti/researcher.asp?idPersona=4

Contributors

Abeer Fareed: 31.07.2007
Ghazi O. Tadmouri: 27.08.2006

Edit History

Asha Deepthi: 11.02.2020
Sarah Al-Haj Ali: 20.11.2004
Sarah Al-Haj Ali: 10.11.2004
Ghazi O. Tadmouri: 28.02.2004