Rare Pulmonology News

Disease Profile

Charcot-Marie-Tooth disease type 1

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.
1-5 / 10 000

33,100 - 165,500

US Estimated

1-5 / 10 000

51,350 - 256,750

Europe Estimated

Age of onset

Infancy

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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)

Autosomal dominant demyelinating Charcot-Marie-Tooth disease; CMT1; Hereditary motor and sensory neuropathy type 1;

Summary

Charcot-Marie-Tooth disease type 1 (CMT1) is a type of peripheral neuropathy, a condition affecting the transmission of information between the central nervous system (brain and spinal cord) and the rest of the body. Symptoms often begin between age 5 and 25, and the condition is usually slowly progressive. Signs and symptoms include distal muscle weakness and wasting (atrophy); sensory loss; and slow nerve conduction velocity. It is often associated with pes cavus foot deformity (high arch) and bilateral foot drop. Fewer than 5% of people with CMT1 become wheelchair dependent.[1]

CMT1 is inherited in an autosomal dominant manner. There are 6 different subtypes CMT1A CMT1B, CMT1C, CMT1D and CMT1F/ CMT2E, caused by different pathogenic variants (mutations)involving the PMP22 gene (designated CMT1A), or the MPZ, LITAF, EGR2, PMP22 or NEFL genes.[1]

Treatment may involve physical or occupational therapy; the use of special shoes, braces or other orthopedic devices; surgery for severe pes cavus; canes or wheelchairs for mobility; and pain medication as needed.[1][2]

Symptoms

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
30%-79% of people have these symptoms
Kyphoscoliosis
0002751
Peripheral demyelination
0011096
Percent of people who have these symptoms is not available through HPO
Areflexia
Absent tendon reflexes
0001284
Autosomal dominant inheritance
0000006
Autosomal recessive inheritance
0000007
Childhood onset
Symptoms begin in childhood
0011463
Clusters of axonal regeneration
0007233
Cold-induced muscle cramps
0003449
Decreased motor nerve conduction velocity
0003431
Decreased number of peripheral myelinated nerve fibers
0003380
Distal amyotrophy
Distal muscle wasting
0003693
Distal muscle weakness
Weakness of outermost muscles
0002460
Distal sensory impairment
Decreased sensation in extremities
0002936
Foot dorsiflexor weakness
Foot drop
0009027
Hammertoe
Hammer toe
Hammertoes

[ more ]

0001765
Hearing impairment
Deafness
Hearing defect

[ more ]

0000365
Hypertrophic nerve changes
0003382
Hyporeflexia
Decreased reflex response
Decreased reflexes

[ more ]

0001265
Insidious onset
Gradual onset
0003587
Juvenile onset
Signs and symptoms begin before 15 years of age
0003621
Limb muscle weakness
Limb weakness
0003690
Motor delay
0001270
Myelin outfoldings
0004336
Onion bulb formation
0003383
Peripheral neuropathy
0009830
Pes cavus
High-arched foot
0001761
Segmental peripheral demyelination/remyelination
0003481
Sensorineural hearing impairment
0000407
Slow progression
Signs and symptoms worsen slowly with time
0003677
Split hand
Claw hand
Claw hand deformities
Claw hands
Claw-hand deformities
Split-hand

[ more ]

0001171
Steppage gait
High stepping
0003376
Talipes calcaneovalgus
0001884
Tonic pupil
0012074
Ulnar claw
0001178
Upper limb muscle weakness
Decreased arm strength
Weak arm

[ more ]

0003484
Variable expressivity
0003828

Diagnosis

A diagnosis of Charcot-Marie-Tooth disease type 1 (CMT1) can be made based on signs and symptoms and molecular genetic testing.[1] People with symptoms of CMT1 should be evaluated by a neurologist. Evaluation may include a thorough neurological exam, special nerve studies, and consideration of medical and family histories.[1][3] If CMT is suspected, tests that may be ordered include:

  • nerve conduction studies electrodes are placed on the skin over nerves and produce small electric shocks. This stimulates the nerves and provides quantifiable information for the doctor.
  • electromyography (EMG) involves inserting a needle electrode through the skin to measure the bioelectrical activity of muscles. Specific abnormalities in the readings can be useful in characterizing the distribution and severity of peripheral nerve involvement.[3]

A clinical diagnosis may be considered in individuals with:

  • progressive peripheral motor and sensory neuropathy
  • slow nerve conduction velocity (NCV)
  • palpably enlarged nerves, especially the ulnar nerve at the elbow and the greater auricular nerve running along the side of the neck
  • a family history consistent with autosomal dominant inheritance[1]

Genetic testing results can usually confirm a diagnosis.[3] Different genetic testing strategies have been proposed in people with symptoms of CMT1, as several genes are associated with the condition. One testing strategy involves testing a single gene at a time, starting with the gene most commonly responsible, and ending with gene least commonly responsible. An alternative genetic testing strategy is using a multi-gene panel that includes all genes of interest.[1] Molecular genetic testing is needed to distinguish the subtype of CMT1 (type A through F), which is based on the responsible gene and mutation.

The Genetic Testing Registry (GTR) provides information about the genetic tests for CMT1. 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.

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

        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.
        • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
        • 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. 
          Charcot-Marie-Tooth disease type 1A
          Charcot-Marie-Tooth disease type 1B
          Charcot-Marie-Tooth disease type 1C
          Charcot-Marie-Tooth disease type 1D
          Charcot-Marie-Tooth disease type 1E
          Charcot-Marie-Tooth disease type 1F / 2E
        • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.

          References

          1. Bird TD. Charcot-Marie-Tooth Neuropathy Type 1. GeneReviews. March 26, 2015; https://www.ncbi.nlm.nih.gov/books/NBK1205/.
          2. Charcot-Marie-Tooth Disease Fact Sheet. National Institute of Neurological Disorders and Stroke Website. May, 2017; https://www.ninds.nih.gov/disorders/charcot_marie_tooth/detail_charcot_marie_tooth.htm.
          3. Charcot-Marie-Tooth Disease Fact Sheet. NINDS. January 14, 2016; https://www.ninds.nih.gov/disorders/charcot_marie_tooth/detail_charcot_marie_tooth.htm.
          4. Davide Pareyson, Chiara Pisciotta. Charcot-Marie-Tooth disease type 1. Orphanet. March, 2016; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=65753.
          5. Divakara Kedlaya. Charcot-Marie-Tooth Disease. Medscape Reference. March 14, 2016; https://emedicine.medscape.com/article/1232386-overview.

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