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Disease Profile

Charcot-Marie-Tooth disease type 2F

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of onset

Adolescent

ICD-10

G60.0

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

CMT 2F; Charcot-Marie-Tooth disease, axonal, Type 2F; Charcot-Marie-Tooth disease, neuronal, Type 2F;

Categories

Congenital and Genetic Diseases; Nervous System Diseases

Summary

Charcot-Marie-Tooth disease type 2F (CMT2F) is a genetic disorder of the peripheral nerves. The subtypes of CMT type 2 (including type 2F) have similar features and are distinguished only by their disease-causing genes. Signs and symptoms usually begin between the ages of 5 and 25 and typically include slowly progressive weakness and atrophy of distal muscles in the feet and/or hands, usually associated with decreased tendon reflexes and mild or no sensory loss. Nerve conduction velocities are usually normal or near-normal. CMT2F is caused by mutations in the HSPB1 gene and is inherited in an autosomal dominant manner. Management may include occupational and physical therapy; special shoes; surgery as needed; mobility aids; and other supportive treatments.[1]

Symptoms

The subtypes of Charcot-Marie-Tooth type 2, including type 2F, have similar signs and symptoms. Affected individuals usually become symptomatic between the ages of 5 and 25, though onset can range from infancy to after the third decade of life. The most common first symptom is weakness of the feet and ankles, followed by slowly progressive weakness and atrophy of distal muscles in the feet and/or hands. Individuals often have decreased tendon reflexes and mild or no sensory loss.

Adults with CMT2 often have bilateral foot drop, symmetric atrophy of muscles below the knee (stork leg appearance) and absent tendon reflexes in the legs. Mild sensory deficits of position, vibration, pain or temperature may occur in the feet, or sensation may be intact. Pain (especially in the feet) is reported by about 20%-40% of affected individuals. Other features that may be associated with CMT2 in a few individuals include hearing impairment; vocal cord or phrenic nerve involvement (which may result in difficulty with speech or breathing); restless legs; and sleep apnea.

CMT2 is progressive over many years, but affected individuals often experience long periods without obvious progression. In some individuals, the condition may be so mild that it goes unrecognized. Affected individuals have a normal life span.[1]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Distal lower limb amyotrophy
0008944
EMG: chronic denervation signs
0003444
Impaired pain sensation
Decreased pain sensation
0007328
Impaired temperature sensation
Abnormality of temperature sensation
Loss of temperature sensation

[ more ]

0010829
Limb fasciculations
0007289
Lower limb muscle weakness
Lower extremity weakness
Lower limb weakness
Muscle weakness in lower limbs

[ more ]

0007340
Peripheral axonal neuropathy
0003477
Reduced tendon reflexes
0001315
Steppage gait
High stepping
0003376
Talipes equinovarus
Club feet
Club foot
Clubfeet
Clubfoot

[ more ]

0001762
Upper limb amyotrophy
0009129
Percent of people who have these symptoms is not available through HPO
Areflexia
Absent tendon reflexes
0001284
Autosomal dominant inheritance
0000006
Chronic axonal neuropathy
0007267
Decreased motor nerve conduction velocity
0003431
Distal amyotrophy
Distal muscle wasting
0003693
Distal muscle weakness
Weakness of outermost muscles
0002460
Distal sensory impairment
Decreased sensation in extremities
0002936
Fasciculations
Muscle twitch
0002380
Foot dorsiflexor weakness
Foot drop
0009027
Hyporeflexia
Decreased reflex response
Decreased reflexes

[ more ]

0001265
Muscle spasm
0003394
Pes cavus
High-arched foot
0001761
Split hand
Claw hand
Claw hand deformities
Claw hands
Claw-hand deformities
Split-hand

[ more ]

0001171
Ulnar claw
0001178

Cause

Charcot-Marie-Tooth disease type 2F (CMT2F) is caused by mutations in the HSPB1 gene. This gene provides instructions for making a protein (heat shock protein beta-1) which helps protect cells under adverse conditions. Heat shock proteins appear to be involved in activities such as cell movement, stabilizing the cell's framework, folding and stabilizing new proteins, repairing damaged proteins, and muscle contraction. Heat shock protein beta-1 is particularly abundant in nerve and muscle cells. In nerve cells, it helps to organize a network of threads that maintain the diameter of axons (neurofilaments), which are needed to transmit nerve impulses efficiently.

It is unclear exactly how HSPB1 mutations lead to the axon abnormalities characteristic of CMT2F. Researchers suggest that mutations lead to an altered protein which clusters together and interferes with nerve cell function. Another possibility is that the altered protein disrupts the assembly of neurofilaments, which in turn may impair the transmission of nerve impulses.

Diagnosis

Yes. GeneTests lists the names of laboratories that are performing clincial genetic testing for Charcot-Marie-Tooth disease type 2F. To view the contact information for these laboratories, click here. Please note that most of the laboratories listed through GeneTests do not accept direct contact from patients and their families; therefore, if you are interested in learning more, you will need to work with a health care provider or a genetics professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

    Treatment

    Treatment for Charcot-Marie-Tooth disease type 2 mainly focuses on the specific symptoms present. Affected individuals are often managed by a team of various specialists that includes neurologists, physiatrists, orthopedic surgeons, and physical and occupational therapists.

    Depending on the individual's signs and symptoms, the following may be indicated:[1]

    • Special shoes, including those with good ankle support
    • Ankle/foot orthoses (AFO) to correct foot drop and aid with walking
    • Orthopedic surgery to correct severe pes cavus
    • Forearm crutches or canes for stability (fewer than 5% of affected individuals need wheelchairs)
    • Treatment of sleep apnea or restless legs
    • Treatment of pain and depression as needed

    Organizations

    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Organizations Supporting this Disease

      Organizations Providing General Support

        Learn more

        These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

        Where to Start

        • The Muscular Dystrophy Association has developed an information page entitled "Surgery Sometimes, Bracing Often, Caution Always: Caring for the CMT-affected Foot." Click on Muscular Dystrophy Association to view this information page.
        • Genetics Home Reference (GHR) contains information on Charcot-Marie-Tooth disease type 2F. This website is maintained by the National Library of Medicine.
        • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

          In-Depth Information

          • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
          • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
          • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
          • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
          • PubMed is a searchable database of medical literature and lists journal articles that discuss Charcot-Marie-Tooth disease type 2F. Click on the link to view a sample search on this topic.

            References

            1. Thomas D. Bird. Charcot-Marie-Tooth Neuropathy Type 2. GeneReviews. July 5, 2012; https://www.ncbi.nlm.nih.gov/books/NBK1285/. Accessed 7/31/2012.
            2. HSPB1. Genetics Home Reference. January 2010; https://ghr.nlm.nih.gov/gene/HSPB1. Accessed 7/31/2012.

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