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Charcot-Marie-Tooth Neuropathy Type 2A

Synonyms: CMT2A, Hereditary and Motor Sensory Neuropathy IIA, HMSN2A, HMSNIIA
, MD, PhD
Department of Human Genetics
University of Miami Miller School of Medicine
Miami, Florida

Initial Posting: ; Last Update: August 1, 2013.


Clinical characteristics.

Charcot-Marie-Tooth hereditary neuropathy type 2A (CMT2A) is a classic axonal peripheral sensorimotor neuropathy characterized by earlier and more severe involvement of the lower extremities than the upper extremities, distal upper-extremity involvement as the neuropathy progresses, more prominent motor deficits than sensory deficits, and normal (>42 m/s) or only slightly decreased nerve conduction velocities (NCVs). Postural tremor is common. Most affected individuals develop symptoms in the first or second decade. It has recently been suggested that CMT2A represents more than 90% of the severe dominant CMT2 cases. However, milder late-onset cases and unusual presentations have also been described.


The diagnosis is established by clinical and molecular genetic findings. MFN2 is the only gene in which pathogenic variants are known to cause CMT2A.


Treatment of manifestations: Treatment by a team including a neurologist, physiatrist, orthopedic surgeon, and physical and occupational therapists; special shoes and/or ankle/foot orthoses to correct foot drop and aid walking; surgery as needed for severe pes cavus; forearm crutches, canes, wheelchairs as needed for mobility; exercise as tolerated; acetaminophen or nonsteroidal anti-inflammatory agents for musculoskeletal pain; treatment of neuropathic pain with tricyclic antidepressants or drugs like carbamazepine or gabapentin.

Surveillance: Annual neurologic evaluation of gait, strength, and visual acuity.

Agents/circumstances to avoid: Obesity (which makes ambulation more difficult); medications (e.g., vincristine, isoniazid, nitrofurantoin) known to cause nerve damage; alcohol and malnutrition (which can cause or exacerbate neuropathy).

Other: Career/employment counseling.

Genetic counseling.

CMT2A is inherited in an autosomal dominant manner. Most individuals diagnosed with CMT2A have an affected parent. The proportion of cases caused by de novo pathogenic variants is unknown. Each child of an individual with CMT2A has a 50% chance of inheriting the pathogenic variant. Prenatal diagnosis for pregnancies at increased risk for CMT2A is possible if the pathogenic variant has been identified in an affected family member.


Clinical Diagnosis

Charcot-Marie-Tooth hereditary neuropathy type 2A (CMT2A) is a classic axonal peripheral sensorimotor neuropathy diagnosed by molecular genetic testing of MFN2.

No specific findings distinguish CMT2A from other types of CMT2. However, in young and severely affected individuals with CMT2, MFN2 pathogenic variants are the most frequent cause of disease. Typical findings include the following:

  • Involvement of the lower extremities earlier and more severely than the upper extremities
  • Involvement of the distal upper extremities as the neuropathy progresses
  • Motor deficits more prominent than sensory deficits
  • Normal (>42 m/s) or only slightly decreased nerve conduction velocities (NCVs) [Saito et al 1997, Züchner et al 2004]
  • Onset before age ten years (however, a wide range of age of onset has been reported)

Molecular Genetic Testing

Gene. MFN2 is the only gene in which pathogenic variants are known to cause CMT2A.

Table 1.

Molecular Genetic Testing Used in Charcot-Marie-Tooth Neuropathy Type 2A

Gene 1Proportion of CMT2A Attributed to Mutation of This GeneTest MethodVariants Detected 2
MFN2Nearly 100%Sequence analysis 3 / scanning for pathogenic variants 4Sequence variants
Sequence analysis of select exons 3, 5Sequence variants in select exons
Deletion/duplication analysis 6Exon and whole-gene deletions/duplications 7

See Molecular Genetics for information on allelic variants.


Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Pathogenic variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.


Sequence analysis and scanning of the entire gene for pathogenic variants can have similar variant detection frequencies; however, variant detection rates for scanning may vary considerably between laboratories depending on the specific protocol used.


Select exons may vary by laboratory.


Testing that identifies exon and whole-gene deletions/duplications not readily detectable by sequence analysis of the coding and flanking intronic regions of genomic DNA; included in the variety of methods that may be used are: quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and chromosomal microarray (CMA) that includes this gene/chromosome segment.


Testing Strategy

To confirm/establish the diagnosis in a proband, identification of a pathogenic variant in MFN2 is necessary.


MFN2 sequence analysis should be performed first. If no pathogenic variant is found by sequence analysis, deletion/duplication analysis of MFN2 should be considered.


If no pathogenic variant in MFN2 is identified by deletion/duplication analaysis, iterative molecular genetic testing strategies have been suggested for CMT based on extensive genetic testing results [Saporta et al 2011].

Predictive testing for at-risk asymptomatic adult family members requires prior identification of the pathogenic variant in the family.

Prenatal diagnosis and preimplantation genetic diagnosis (PGD) for at-risk pregnancies require prior identification of the pathogenic variant in the family.

Clinical Characteristics

Clinical Description

The age at onset and disease progression of Charcot-Marie-Tooth hereditary neuropathy type 2A (CMT2A) vary within and among families; onset ranges from age one year to the sixth decade. Most individuals develop symptoms in the first or second decade. The initial finding is often foot drop or foot weakness. Pes cavus foot deformity may occur.

Motor signs (weakness and atrophy) predominate, but mild sensory loss in the feet is common. Tendon reflexes are usually absent, but occasionally intact.

Some individuals with MFN2 pathogenic variants are asymptomatic and have only mild findings on examination; however, those could eventually convert to late-onset cases [Lawson et al 2005].

Postural tremor is common [Muglia et al 2001, Bissar-Tadmouri et al 2004].

Affected individuals with early onset (age <10 years) tend to have more severe disability than those with later onset [Chung et al 2006]. Those with early onset may show optic atrophy, hoarse voice, and proximal weakness. Subacute onset of optic atrophy with subsequent slow recovery in 60% of individuals with early onset was reported by Züchner et al [2006], and confirmed by Chung et al [2006] and Verhoeven et al [2006].

The disease course is progressive. Although some individuals become dependent on crutches or a wheelchair, most do not [Muglia et al 2001]. Life span is usually not reduced.

Neuroimaging. Periventricular and subcortical white matter lesions on brain MRI have been reported in a few individuals [Chung et al 2006, Züchner et al 2006].

Neuropathology. Neuropathologic findings include loss of myelinated nerve fibers (especially large fibers), mitochondrial abnormalities and, rarely, onion bulb formation [Saito et al 1997, Muglia et al 2001, Verhoeven et al 2006].

Genotype-Phenotype Correlations

No apparent genotype-phenotype correlation has been reported except in one family in which truncation of the protein led to a more severe phenotype with visual impairment [Züchner et al 2006]. Some rare families with recessive compound heterozygous changes in MFN2 have been reported which all showed early onset of disease [Polke et al 2011]. Individuals with optic atrophy (HMSN VI) tend to show a more severe phenotype; several of these individuals were found to have a de novo pathogenic variant [Züchner et al 2006].


The penetrance is considered to be complete. Some individuals with MFN2 pathogenic variants are asymptomatic and have only mild findings on examination; in these cases, however, the disease may prove to be late onset [Lawson et al 2005].


While some authors have considered the possibility of anticipation in CMT2A, it has not been reported [Muglia et al 2001].


CMT2A is an axonal neuropathy (indicated by the number 2) and was the first CMT2 form to be linked to a chromosomal locus (indicated by the letter A).

In addition to the pure CMT2A phenotype, CMT2 with optic atrophy, also known as hereditary motor and sensory neuropathy VI (HMSN VI), has been reported in a number of individuals [Züchner et al 2006] (see Genetically Related Disorders).

Chung et al [2006] suggested the division into "early-onset severe CMT2A phenotype" and "late-onset mild CMT2A phenotype" owing to MFN2 pathogenic variants. All reported persons with HMSN VI with MFN2 pathogenic variants had early-onset severe CMT2.

All reported persons with HMSN VI with MFN2 pathogenic variants had early-onset severe CMT2.


The proportion of CMT caused by pathogenic variants in MFN2 varies by study:

  • Züchner et al [2004] reported seven MFN2 pathogenic variants in 36 families with CMT2, indicating that 19.5% of CMT2 could be caused by mutation of this gene.
  • Chung et al [2006] reported that 24% of 62 families with CMT2 in South Korea had pathogenic variants in MFN2.
  • Verhoeven et al [2006] reported that 33% of families with CMT2 in a European/USA study had pathogenic variants in MFN2.
  • Engelfried et al [2006] reported that 8% (6/73) of persons with CMT2, including simplex cases (i.e., a single occurrence in a family), had MFN2 pathogenic variants.
  • Feely et al [2011] reported that CMT2A accounted for 91% of severely impaired individuals with CMT2 but only 11% of mildly or moderately impaired people.
  • The majority of reported cases of optic atrophy associated with the CMT2A phenotype (previously called HMSN VI) resulted from de novo MFN2 pathogenic variants.

Differential Diagnosis

See Charcot-Marie-Tooth Hereditary Neuropathy Overview.

All CMT forms in which axonal phenotypes have been reported, including CMT1A (caused by pathogenic variants in PMP22), CMT1B (caused by pathogenic variants in MPZ), and CMTX (caused by pathogenic variants in GJB1, the gene encoding the protein connexin 32), need to be considered in the differential diagnosis of CMT2A.

MFN2 pathogenic variants may prove to be the most common cause of autosomal dominant CMT2. As many as one third of all individuals with CMT2 with a positive family history have a pathogenic variant in MFN2 [Verhoeven et al 2006]. Thus, testing of MFN2 is probably the first genetic test to consider in families with an axonal neuropathy demonstrating male-to-male transmission.


Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with Charcot-Marie-Tooth hereditary neuropathy type 2A (CMT2A), the following evaluations are recommended:

  • Neurologic examination
  • EMG with NCV
  • Visual evoked potentials
  • Consultation with a clinical geneticist and/or genetic counselor

Treatment of Manifestations

The affected individual is often managed by a multidisciplinary team that includes a neurologist, physiatrist, orthopedic surgeon, and physical and occupational therapists [Carter et al 1995]. Treatment is symptomatic and may include the following:

  • Daily heel cord stretching exercises to prevent Achilles tendon shortening
  • Special shoes, including those with good ankle support
  • Ankle/foot orthoses to correct foot drop and aid walking [Carter et al 1995]
  • Orthopedic surgery to correct severe pes cavus deformity [Holmes & Hansen 1993, Guyton & Mann 2000]
  • Forearm crutches or canes for gait stability
  • Wheelchairs for mobility because of gait instability
  • Exercise within the individual's capability
  • Treatment of musculoskeletal pain with acetaminophen or nonsteroidal anti-inflammatory agents [Carter et al 1998]
  • Treatment of neuropathic pain with tricyclic antidepressants or drugs such as carbamazepine or gabapentin
  • Career and employment counseling because of persistent weakness of hands and/or feet


Annual neurologic evaluation of gait, strength, and visual acuity is appropriate.

Agents/Circumstances to Avoid

Obesity is to be avoided because it makes walking more difficult.

Medications that are toxic or potentially toxic to persons with CMT comprise a spectrum of risk ranging from definite high risk to negligible risk. Click here (pdf) for an up-to-date list.

Evaluation of Relatives at Risk

See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.

Therapies Under Investigation

Dyck et al [1982], Donaghy et al [2000], and Ginsberg et al [2004] have described a few individuals with CMT1 and sudden deterioration in whom treatment with steroids (prednisone) or intravenous immunoglobulin has produced variable levels of improvement. No similar report on CMT2A exists.

Search in the US and in Europe for access to information on clinical studies for a wide range of diseases and conditions.

Genetic Counseling

Genetic counseling is the process of providing individuals and families with information on the nature, inheritance, and implications of genetic disorders to help them make informed medical and personal decisions. The following section deals with genetic risk assessment and the use of family history and genetic testing to clarify genetic status for family members. This section is not meant to address all personal, cultural, or ethical issues that individuals may face or to substitute for consultation with a genetics professional. —ED.

Mode of Inheritance

Charcot-Marie-Tooth neuropathy type 2A (CMT2A) is inherited an autosomal dominant manner.

Risk to Family Members

Parents of a proband

  • Most individuals diagnosed with CMT2A have an affected parent.
  • A proband with CMT2A may have the disorder as the result of a de novo pathogenic variant. The proportion of cases caused by de novo pathogenic variants is unknown.
  • It is appropriate to evaluate the parents of an individual with CMT2A in order to determine which, if either, is symptomatic, both to assure appropriate medical management for that individual and for genetic counseling of the family.

Note: Although most individuals diagnosed with CMT2A have an affected parent, the family history may appear to be negative because of failure to recognize the disorder in family members, early death of the parent before the onset of symptoms, or late onset of the disease in the affected parent.

Sibs of a proband

  • The risk to the sibs depends on the genetic status of the proband's parents.
  • If a parent has a pathogenic variant, the risk to the sibs is 50%.
  • When the parents are clinically unaffected, the risk to the sibs of a proband appears to be low. No instances of germline mosaicism have been reported, although it remains a possibility.

Offspring of a proband. Each child of an individual with CMT2A has a 50% chance of inheriting the pathogenic variant.

Other family members of a proband. The risk to other family members depends on the status of the proband's parents. If a parent is affected, his or her family members are at risk.

Related Genetic Counseling Issues

Considerations in families with an apparent de novo pathogenic variant. When neither parent of a proband with an autosomal dominant condition has clinical evidence of the disorder or the pathogenic variant, it is likely that the proband has a de novo pathogenic variant. However, possible non-medical explanations including alternate paternity or maternity (e.g., with assisted reproduction) or undisclosed adoption could also be explored.

Family planning

  • The optimal time for determination of genetic risk and discussion of the availability of prenatal testing is before pregnancy.
  • It is appropriate to offer genetic counseling (including discussion of potential risks to offspring and reproductive options) to young adults who are affected or at risk.

DNA banking is the storage of DNA (typically extracted from white blood cells) for possible future use. Because it is likely that testing methodology and our understanding of genes, allelic variants, and diseases will improve in the future, consideration should be given to banking DNA of affected individuals.

Prenatal Testing and Preimplantation Genetic Diagnosis

Once the pathogenic variant has been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic diagnosis are possible.

Differences in perspective may exist among medical professionals and within families regarding the use of prenatal testing, particularly if the testing is being considered for the purpose of pregnancy termination rather than early diagnosis. While most centers would consider decisions regarding prenatal testing to be the choice of the parents, discussion of these issues is appropriate.


GeneReviews staff has selected the following disease-specific and/or umbrella support organizations and/or registries for the benefit of individuals with this disorder and their families. GeneReviews is not responsible for the information provided by other organizations. For information on selection criteria, click here.

  • Association CMT France
    Phone: 820 077 540; 2 47 27 96 41
  • Charcot-Marie-Tooth Association (CMTA)
    PO Box 105
    Glenolden PA 19036
    Phone: 800-606-2682 (toll-free); 610-499-9264
    Fax: 610-499-9267
  • European Charcot-Marie-Tooth Consortium
    Department of Molecular Genetics
    University of Antwerp
    Antwerp Antwerpen B-2610
    Fax: 03 2651002
  • Hereditary Neuropathy Foundation, Inc.
    432 Park Avenue South
    4th Floor
    New York NY 10016
    Phone: 855-435-7268 (toll-free); 212-722-8396
    Fax: 917-591-2758
  • My46 Trait Profile
  • National Library of Medicine Genetics Home Reference
  • NCBI Genes and Disease
    Institute of Genetic Medicine
    University of Newcastle upon Tyne
    International Centre for Life
    Newcastle upon Tyne NE1 3BZ
    United Kingdom
    Phone: 44 (0)191 241 8617
    Fax: 44 (0)191 241 8770
  • Association Francaise contre les Myopathies (AFM)
    1 Rue de l'International
    Evry cedex 91002
    Phone: +33 01 69 47 28 28
  • European Neuromuscular Centre (ENMC)
    Lt Gen van Heutszlaan 6
    3743 JN Baarn
    Phone: 31 35 5480481
    Fax: 31 35 5480499
  • Muscular Dystrophy Association - USA (MDA)
    222 South Riverside Plaza
    Suite 1500
    Chicago IL 60606
    Phone: 800-572-1717
  • Muscular Dystrophy UK
    61A Great Suffolk Street
    London SE1 0BU
    United Kingdom
    Phone: 0800 652 6352 (toll-free); 020 7803 4800
  • RDCRN Patient Contact Registry: Inherited Neuropathies Consortium

Molecular Genetics

Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —ED.

Table A.

Charcot-Marie-Tooth Neuropathy Type 2A: Genes and Databases

Locus NameGeneChromosome LocusProteinLocus-Specific DatabasesHGMDClinVar
CMT2A2MFN21p36​.22Mitofusin-2MFN2 homepage - Leiden Muscular Dystrophy pages
IPN Mutations, MFN2

Data are compiled from the following standard references: gene from HGNC; chromosome locus from OMIM; protein from UniProt. For a description of databases (Locus Specific, HGMD, ClinVar) to which links are provided, click here.

Table B.

OMIM Entries for Charcot-Marie-Tooth Neuropathy Type 2A (View All in OMIM)


Molecular Genetic Pathogenesis

The disease mechanism leading to CMT is unknown.


Gene structure. MFN2 has 17 exons and 4,546 nucleotides in the open reading frame. For a detailed summary of gene and protein information, see Table A, Gene.

Pathogenic variants. To date, more than 50 pathogenic variants have been reported. The majority were missense variants; frameshift and nonsense variants have also been reported [Züchner et al 2004, Verhoeven et al 2006].

Normal gene product. MFN2 encodes a large GTPase of 757 amino acids that is situated at the outer mitochondrial membrane [Rojo et al 2002]. It has been shown that MFN2 accounts for the fusion/fission balance of mitochondria [Santel & Fuller 2001]. Recently, evidence for direct involvement of MFN2 in fusion of mitochondria has been reported [Koshiba et al 2004]. The gene is ubiquitously expressed [Santel & Fuller 2001].

Larger insertions and duplications are not known to be involved in CMT2A, but could represent rare mutational mechanisms.

Abnormal gene product. Most pathogenic variants are in the GTPase domain, but other parts of the protein are also affected. The GTPase domain may be crucial for the development of peripheral neuropathy. Pathogenic variants may affect both mitochondrial fusion and energy metabolism [Pich et al 2005]. Baloh et al [2007] reported altered axonal mitochondrial transport resulting from CMT2A-related MFN2 pathogenic variants.


Literature Cited

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  • Bissar-Tadmouri N, Nelis E, Züchner S, Parman Y, Deymeer F, Serdaroglu P, De Jonghe P, Van Gerwen V, Timmerman V, Schröder JM, Battaloglu E. Absence of KIF1B mutation in a large Turkish CMT2A family suggests involvement of a second gene. Neurology. 2004;62:1522–5. [PubMed: 15136675]
  • Carter GT, Abresch RT, Fowler WM Jr, Johnson ER, Kilmer DD, McDonald CM. Profiles of neuromuscular diseases. Hereditary motor and sensory neuropathy, types I and II. Am J Phys Med Rehabil. 1995;74:S140–9. [PubMed: 7576421]
  • Carter GT, Jensen MP, Galer BS, Kraft GH, Crabtree LD, Beardsley RM, Abresch RT, Bird TD. Neuropathic pain in Charcot-Marie-Tooth disease. Arch Phys Med Rehabil. 1998;79:1560–4. [PubMed: 9862301]
  • Chung KW, Cho SY, Hwang SJ, Kim KH, Yoo JH, Kwon O, Kim SM, Sunwoo IN, Züchner S, Choi BO. Early-onset stroke associated with a mutation in mitofusin 2. Neurology. 2008;70:2010–1. [PubMed: 18490623]
  • Chung KW, Kim SB, Park KD, Choi KG, Lee JH, Eun HW, Suh JS, Hwang JH, Kim WK, Seo BC, Kim SH, Son IH, Kim SM, Sunwoo IN, Choi BO. Early onset severe and late-onset mild Charcot-Marie-Tooth disease with mitofusin 2 (MFN2) mutations. Brain. 2006;129:2103–18. [PubMed: 16835246]
  • Donaghy M, Sisodiya SM, Kennett R, McDonald B, Haites N, Bell C. Steroid responsive polyneuropathy in a family with a novel myelin protein zero mutation. J Neurol Neurosurg Psychiatry. 2000;69:799–805. [PMC free article: PMC1737181] [PubMed: 11080236]
  • Dyck PJ, Swanson CJ, Low PA, Bartleson JD, Lambert EH. Prednisone-responsive hereditary motor and sensory neuropathy. Mayo Clin Proc. 1982;57:239–46. [PubMed: 7070119]
  • Engelfried K, Vorgerd M, Hagedorn M, Haas G, Gilles J, Epplen JT, Meins M. Charcot-Marie-Tooth neuropathy type 2A: novel mutations in the mitofusin 2 gene (MFN2). BMC Med Genet. 2006;7:53. [PMC free article: PMC1524942] [PubMed: 16762064]
  • Feely SM, Laura M, Siskind CE, Sottile S, Davis M, Gibbons VS, Reilly MM, Shy ME. MFN2 mutations cause severe phenotypes in most patients with CMT2A. Neurology. 2011;76:1690–6. [PMC free article: PMC3100135] [PubMed: 21508331]
  • Ginsberg L, Malik O, Kenton AR, Sharp D, Muddle JR, Davis MB, Winer JB, Orrell RW, King RH. Coexistent hereditary and inflammatory neuropathy. Brain. 2004;127:193–202. [PubMed: 14607795]
  • Guyton GP, Mann RA. The pathogenesis and surgical management of foot deformity in Charcot-Marie-Tooth disease. Foot Ankle Clin. 2000;5:317–26. [PubMed: 11232233]
  • Holmes JR, Hansen ST Jr. Foot and ankle manifestations of Charcot-Marie-Tooth disease. Foot Ankle. 1993;14:476–86. [PubMed: 8253442]
  • Koshiba T, Detmer SA, Kaiser JT, Chen H, McCaffery JM, Chan DC. Structural basis of mitochondrial tethering by mitofusin complexes. Science. 2004;305:858–62. [PubMed: 15297672]
  • Lawson VH, Graham BV, Flanigan KM. Clinical and electrophysiologic features of CMT2A with mutations in the mitofusin 2 gene. Neurology. 2005;65:197–204. [PubMed: 16043786]
  • Muglia M, Zappia M, Timmerman V, Valentino P, Gabriele AL, Conforti FL, De Jonghe P, Ragno M, Mazzei R, Sabatelli M, Nicoletti G, Patitucci AM, Oliveri RL, Bono F, Gambardella A, Quattrone A. Clinical and genetic study of a large Charcot-Marie-Tooth type 2A family from southern Italy. Neurology. 2001;56:100–3. [PubMed: 11148244]
  • Pich S, Bach D, Briones P, Liesa M, Camps M, Testar X, Palacín M, Zorzano A. The Charcot-Marie-Tooth type 2A gene product, Mfn2, up-regulates fuel oxidation through expression of OXPHOS system. Hum Mol Genet. 2005;14:1405–15. [PubMed: 15829499]
  • Polke JM, Laurá M, Pareyson D, Taroni F, Milani M, Bergamin G, Gibbons VS, Houlden H, Chamley SC, Blake J, Devile C, Sandford R, Sweeney MG, Davis MB, Reilly MM. Recessive axonal Charcot-Marie-Tooth disease due to compound heterozygous mitofusin 2 mutations. Neurology. 2011;77:168–73. [PMC free article: PMC3140074] [PubMed: 21715711]
  • Rojo M, Legros F, Chateau D, Lombès A. Membrane topology and mitochondrial targeting of mitofusins, ubiquitous mammalian homologs of the transmembrane GTPase Fzo. J Cell Sci. 2002;115:1663–74. [PubMed: 11950885]
  • Saito M, Hayashi Y, Suzuki T, Tanaka H, Hozumi I, Tsuji S. Linkage mapping of the gene for Charcot-Marie-Tooth disease type 2 to chromosome 1p (CMT2A) and the clinical features of CMT2A. Neurology. 1997;49:1630–5. [PubMed: 9409358]
  • Santel A, Fuller MT. Control of mitochondrial morphology by a human mitofusin. J Cell Sci. 2001;114:867–74. [PubMed: 11181170]
  • Saporta AS, Sottile SL, Miller LJ, Feely SM, Siskind CE, Shy ME. Charcot-Marie-Tooth disease subtypes and genetic testing strategies. Ann Neurol. 2011;69:22–33. [PMC free article: PMC3058597] [PubMed: 21280073]
  • Verhoeven K, Claeys KG, Züchner S, Schröder JM, Weis J, Ceuterick C, Jordanova A, Nelis E, De Vriendt E, Van Hul M, Seeman P, Mazanec R, Saifi GM, Szigeti K, Mancias P, Butler IJ, Kochanski A, Ryniewicz B, De Bleecker J, Van den Bergh P, Verellen C, Van Coster R, Goemans N, Auer-Grumbach M, Robberecht W, Milic Rasic V, Nevo Y, Tournev I, Guergueltcheva V, Roelens F, Vieregge P, Vinci P, Moreno MT, Christen HJ, Shy ME, Lupski JR, Vance JM, De Jonghe P, Timmerman V. MFN2 mutation distribution and genotype/phenotype correlation in Charcot-Marie-Tooth type 2. Brain. 2006;129:2093–102. [PubMed: 16714318]
  • Vucic S, Kennerson M, Zhu D, Miedema E, Kok C, Nicholson GA. CMT with pyramidal features. Charcot-Marie-Tooth. Neurology. 2003;60:696–9. [PubMed: 12601114]
  • Zhu D, Kennerson ML, Walizada G, Züchner S, Vance JM, Nicholson GA. Charcot-Marie-Tooth with pyramidal signs is genetically heterogeneous: families with and without MFN2 mutations. Neurology. 2005;65:496–7. [PubMed: 16087932]
  • Züchner S, De Jonghe P, Jordanova A, Claeys KG, Guergueltcheva V, Cherninkova S, Hamilton SR, Van Stavern G, Krajewski KM, Stajich J, Tournev I, Verhoeven K, Langerhorst CT, de Visser M, Baas F, Bird T, Timmerman V, Shy M, Vance JM. Axonal neuropathy with optic atrophy is caused by mutations in mitofusin 2. Ann Neurol. 2006;59:276–81. [PubMed: 16437557]
  • Züchner S, Mersiyanova IV, Muglia M, Bissar-Tadmouri N, Rochelle J, Dadali EL, Zappia M, Nelis E, Patitucci A, Senderek J, Parman Y, Evgrafov O, Jonghe PD, Takahashi Y, Tsuji S, Pericak-Vance MA, Quattrone A, Battaloglu E, Polyakov AV, Timmerman V, Schröder JM, Vance JM. Mutations in the mitochondrial GTPase mitofusin 2 cause Charcot-Marie-Tooth neuropathy type 2A. Nat Genet. 2004;36:449–51. [PubMed: 15064763]

Suggested Reading

  • Lupski JR, Garcia CA. Charcot-Marie-Tooth peripheral neuropathies and related disorders. In: Valle D, Beaudet AL, Vogelstein B, Kinzler KW, Antonarakis SE, Ballabio A, Gibson K, Mitchell G, eds. The Online Metabolic and Molecular Bases of Inherited Disease (OMMBID). New York, NY: McGraw-Hill. Chap 227.

Chapter Notes

Revision History

  • 1 August 2013 (me) Comprehensive update posted live
  • 10 June 2010 (cd) Revision: edits to Agents/Circumstances to Avoid
  • 12 September 2007 (me) Comprehensive update posted live
  • 23 January 2006 (cd) Revision: prenatal diagnosis for MFN2 mutations clinically available
  • 18 February 2005 (me) Review posted live
  • 13 September 2004 (sz) Original submission
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