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Disease Profile

Charcot-Marie-Tooth disease type 2P

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)

CMT2P; Charcot-Marie-Toothe disease, axonal, type 2P ; CHARCOT-MARIE-TOOTH NEUROPATHY, TYPE 2P

Categories

Congenital and Genetic Diseases; Nervous System Diseases

Summary

Charcot-Marie-Tooth disease type 2P (CMT2P) is a subtype of Charcot-Marie-Tooth caused by changes (mutations) in the LRSAM1 gene. The onset of symptoms commonly occurs between 20 and 40 years of age and the disease seems to be relatively mild and benign. Symptoms may include mild loss of sensation in the fingertips and severe loss of sensation in the feet and legs. The most common type of sensation loss is to vibration, but proprioception (the sense of how we are oriented in space) and perception to pain may also be affected. Individuals with CMT2P may also have muscle twitches (fasciculations) and cramps (in younger patients) and muscular weakness and muscular wasting in the legs, feet and hands (in older individuals). It may be inherited in an autossomal dominant or autossomal recessive pattern.[1][2]

Symptoms

The onset of symptoms in the reported cases is between 20 to 40 years of age and the disease seems to be relatively mild and benign. Affected individuals may have the following signs and symptoms:[1][2]

• Mild loss of sensation on fingertips and severe loss of sensation in feet and legs, most markedly to vibration but also involving proprioception (the sense of how we are oriented in the space) and pain perception.
• Muscle twitches (fasciculations) and cramps in younger patients.
• Muscular weakness in legs and hands in older individuals.
• Wasting of muscles of the hand and legs and feet.
• Absent reflexes.
Motor nerve conduction studies are usually normal.
Needle EMG may show giant motor units potentials (MPU) both in proximal and distal muscles of all patients. The motor unit is a part of the neuromuscular system that contains a cell, its axon, and all of the muscle fibers that it innervates, including the axon's specialized point of connection to the muscle fiber, the neuromuscular junction. In routine needle-electrode examination (electromyography (EMG) of voluntary muscle contraction, the consultant assesses the electrical signal generated by the MUs, termed the "MU action potential" (or MUAP). Needle EMG findings suggestive of denervation include giant MUP.

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
5%-29% of people have these symptoms
Hammertoe
Hammer toe
Hammertoes

[ more ]

0001765
Percent of people who have these symptoms is not available through HPO
Areflexia
Absent tendon reflexes
0001284
Autosomal dominant inheritance
0000006
Axonal degeneration
0040078
Axonal degeneration/regeneration
0003378
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
Impaired distal vibration sensation
0006886
Incomplete penetrance
0003829
Peripheral axonal degeneration
0000764
Pes cavus
High-arched foot
0001761
Slow progression
Signs and symptoms worsen slowly with time
0003677
Steppage gait
High stepping
0003376
Toe walking
Toe-walking
0040083

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

    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.

    In-Depth Information

    • 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.

      References

      1. Engeholm M & cols. A novel mutation in LRSAM1 causes axonal Charcot-Marie-Tooth disease with dominant Inheritance. BMC Neurology. June 3, 2014; 14:118. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4060843/. Accessed 6/26/2015.
      2. Charcot-Marie-Toothe disease, axonal, type 2P. OMIM. February 24, 2015; https://omim.org/entry/614436. Accessed 6/26/2015.

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