Charcot-Marie-Tooth Type 2Z: MORC2 and Genetic Testing
Medically reviewed by Brandon Colby, MD, last reviewed
Charcot-Marie-Tooth disease axonal type 2Z (CMT2Z) is an inherited neuropathy caused by pathogenic variants in the MORC2 gene. It follows an autosomal dominant inheritance pattern, although many cases result from a new variant that is not inherited from either parent. Genetic testing can help confirm the diagnosis.
Understanding Charcot-Marie-Tooth Disease Axonal Type 2Z
Charcot-Marie-Tooth disease (CMT) is a group of inherited conditions that damage the peripheral nerves. Type 2 forms mainly damage the axon, the long fiber that carries the nerve signal.
CMT2Z is caused by pathogenic variants in the MORC2 gene, which provides instructions for making a protein that helps control how DNA is packaged and which genes are switched off. It follows an autosomal dominant inheritance pattern, although some cases result from a new (de novo) variant that is not inherited from either parent.
Symptoms often begin in childhood and include muscle weakness and wasting in the feet and hands. Some people also develop weakness in muscles closer to the body, such as those in the hips and shoulders. The age of onset and severity can vary widely.
Diagnosing Charcot-Marie-Tooth Disease Axonal Type 2Z
A neurological exam and nerve conduction studies can help identify an axonal neuropathy. Because CMT2Z can occur without a family history, genetic testing through a multigene panel, exome sequencing or genome sequencing can help identify the cause. Finding a pathogenic variant associated with CMT2Z in the MORC2 gene can help confirm the diagnosis, and testing the parents may clarify whether the variant was inherited or arose for the first time (de novo).
Uses of Genetic Testing for Charcot-Marie-Tooth Disease Axonal Type 2Z
Genetic testing for CMT2Z can be helpful in several ways:
- Confirming the diagnosis: Finding a pathogenic variant associated with CMT2Z in the MORC2 gene can help confirm the diagnosis and may provide answers after a long search.
- Separating CMT subtypes: Several forms of CMT cause similar symptoms. A clear genetic result can help identify the subtype and guide discussions about care and possible symptoms.
- Family screening and counseling: Relatives may choose testing for the identified pathogenic variant. A genetic counselor can explain the results, discuss the 50% chance of passing the variant to each child and review family planning options.
- Research and clinical trials: Some research studies and trials enroll people by gene. A confirmed genetic diagnosis can make it easier to find studies that fit.
Advancements in Genetic Research for Charcot-Marie-Tooth Disease
MORC2 helps control which genes are switched off in cells. Researchers are studying how pathogenic variants associated with CMT2Z disrupt this process in nerve cells. This work may help identify new targets for treatment.
Related Charcot-Marie-Tooth Articles
- Charcot-Marie-Tooth Disease Type 2: the axonal forms of CMT.
- Charcot-Marie-Tooth, Intermediate: forms with features of both CMT1 and CMT2.
- Charcot-Marie-Tooth Disease: an overview of CMT and its genetics.
Get Tested With Whole Genome Sequencing
Whole genome sequencing reads 100% of your DNA, which includes the genes linked to Charcot-Marie-Tooth disease. Sequencing's Kit Bundles include a Whole Genome Sequencing kit and Next Gen Disease Screening, which analyzes your genome for more than 15,000 conditions. Bring your results to your doctor or a genetic counselor to help guide next steps.
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Frequently Asked Questions About Charcot-Marie-Tooth Disease Axonal Type 2Z
What is CMT axonal type 2Z?
It is an inherited axonal neuropathy that often begins in childhood and causes weakness, muscle wasting and sensory loss in the hands and feet.
What causes it?
It is caused by pathogenic variants in the MORC2 gene, which helps control how DNA is packaged and which genes are turned off.
What are the symptoms?
Symptoms include weakness and wasting of the feet, lower legs and hands, foot deformities, trouble walking and reduced sensation. Some people also have weakness in the hips and shoulders. Severity varies from mild to severe.
How is it inherited?
It is inherited in an autosomal dominant pattern. One altered copy of the gene is enough to cause the condition, so each child of an affected parent has a 50% chance of inheriting the variant. Some people have a new (de novo) variant that was not inherited from either parent.
How is it diagnosed?
A neurologist usually starts with a medical and family history and an exam of strength, reflexes and sensation. Nerve conduction studies and electromyography (EMG) show how well nerves carry signals and whether the problem mainly affects the myelin coating or the nerve fiber (axon). Genetic testing can then confirm the specific cause.
Is there a treatment?
There is currently no cure, but care can help people stay active and independent. Physical and occupational therapy, ankle-foot orthoses (braces), supportive footwear, orthopedic surgery for foot deformities and pain management are commonly used. A neuromuscular specialist can build a care plan with you.
Does Sequencing test for this condition?
Whole genome sequencing reads 100% of your DNA, which includes the MORC2 gene discussed in this article. Sequencing's Kit Bundles include Next Gen Disease Screening, which analyzes your genome for more than 15,000 conditions. You can also upload DNA data from another test for free and search it in Genome Explorer. Results describe variants, not a diagnosis.
Where can I find support or a specialist?
Patient organizations such as the CMT Research Foundation, Charcot-Marie-Tooth Association, Hereditary Neuropathy Foundation and Muscular Dystrophy Canada offer education and support for people and families affected by CMT, and several publish directories of CMT clinics or specialists. They are listed in the resources below, along with an expert written overview from GeneReviews.
Resources
These organizations and resources are provided for education and support. They are not endorsements or medical advice.
- CMT Research Foundation (United States): a patient-led organization focused on funding research toward treatments for CMT.
- CMTRF: Scientific Advisory Board: the medical and scientific advisors who guide the organization.
- Charcot-Marie-Tooth Association (United States): a patient and family organization for all types of CMT.
- CMTA: Find a specialist: the organization's directory of clinics or specialists.
- CMTA: Advisory Board: the medical and scientific advisors who guide the organization.
- Hereditary Neuropathy Foundation (United States): a patient organization for people and families affected by CMT and other inherited neuropathies.
- HNF: Find a specialist: the organization's directory of clinics or specialists.
- HNF: Scientific Advisory Board: the medical and scientific advisors who guide the organization.
- Muscular Dystrophy Canada (Canada): a neuromuscular disease organization that supports people with CMT in Canada.
- Muscular Dystrophy Canada: Medical and Scientific Advisory Committee (MSAC): the medical and scientific advisors who guide the organization.
- GeneReviews: Charcot-Marie-Tooth Hereditary Neuropathy Overview (NCBI Bookshelf): an expert written clinical overview of CMT and its genetics.
References
- Sevilla T, Lupo V, Martínez-Rubio D, et al. Mutations in the MORC2 gene cause axonal Charcot-Marie-Tooth disease. Brain. 2016;139(1):62-72. doi:10.1093/brain/awv311
This article is for education and is not a substitute for professional medical advice, diagnosis, or treatment. Talk to a qualified healthcare provider about your own health.