Understanding Charcot-Marie-Tooth Type 2X and SPG11

Charcot-Marie-Tooth disease axonal type 2X (CMT2X) is an inherited neuropathy caused by pathogenic variants in both copies of the SPG11 gene. It follows an autosomal recessive inheritance pattern, and symptoms often begin in childhood or adolescence. Genetic testing can help confirm the diagnosis.

Understanding Charcot-Marie-Tooth Disease Axonal Type 2X

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.

CMT2X is caused by pathogenic variants in both copies of the SPG11 gene. This gene provides instructions for making spatacsin, a protein that helps maintain nerve fibers and move and recycle materials inside cells.

Symptoms often begin in childhood or adolescence. They include muscle weakness and wasting in the feet and lower legs, foot deformities and numbness. Mild learning difficulties have also been reported in a small number of people with CMT2X.

Diagnosing Charcot-Marie-Tooth Disease Axonal Type 2X

Nerve conduction studies can help identify an axonal neuropathy. Because SPG11-related conditions can affect both peripheral nerves and the brain and spinal cord, doctors may also check for muscle stiffness, unusually strong reflexes or changes on a brain MRI. Genetic testing through a multigene panel, exome sequencing or genome sequencing can help confirm the diagnosis by identifying pathogenic variants in both copies of the SPG11 gene.

Uses of Genetic Testing for Charcot-Marie-Tooth Disease Axonal Type 2X

Genetic testing for CMT2X can be helpful in several ways:

1. Confirming the diagnosis: Finding pathogenic variants associated with CMT2X in both copies of the SPG11 gene can help confirm the diagnosis and may provide answers after a long search.
2. Separating CMT subtypes: Many types of CMT look alike in the clinic. A genetic result identifies the exact subtype, which helps doctors anticipate symptoms and plan care.
3. Family screening and counseling: Parents and siblings may choose testing to learn whether they carry the identified pathogenic variants. A genetic counselor can explain the results, discuss inheritance and review family planning options.
4. 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

Research on SPG11 is helping explain how pathogenic variants in the same gene can cause different conditions, including CMT2X, hereditary spastic paraplegia and motor neuron disease. Following people with CMT2X over time may help researchers better understand how symptoms develop and change.

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.

Shop All Whole Genome Sequencing Kit Bundles

Frequently Asked Questions About Charcot-Marie-Tooth Disease Axonal Type 2X

What is CMT axonal type 2X?

It is an inherited axonal neuropathy that usually starts in childhood or adolescence and causes weakness, muscle wasting and sensory loss in the feet, legs and hands.

What causes it?

It is caused by pathogenic variants associated with CMT2X in both copies of the SPG11 gene, which provides instructions for making spatacsin, a protein that helps cells recycle their contents.

What are the symptoms?

Symptoms include muscle weakness and wasting in the lower legs, foot drop, high arches, difficulty walking and numbness. Mild learning difficulties have also been reported in a small number of people with CMT2X.

How is it inherited?

It is inherited in an autosomal recessive pattern. A person must inherit two altered copies of the gene, one from each parent. Parents are usually carriers without symptoms, and each child of two carriers has a 25% chance of being affected and a 50% chance of being a carrier.

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 SPG11 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

1. Montecchiani C, Pedace L, Lo Giudice T, et al. ALS5/SPG11/KIAA1840 mutations cause autosomal recessive axonal Charcot-Marie-Tooth disease. Brain. 2016;139(1):73-85. doi:10.1093/brain/awv320

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.