Charcot-Marie-Tooth disease type 1A

Title

Other Names:

Charcot-Marie-Tooth disease, demyelinating, type 1A; CMT 1A; Hereditary motor and sensory neuropathy 1A; Charcot-Marie-Tooth disease, demyelinating, type 1A; CMT 1A; Hereditary motor and sensory neuropathy 1A; HMSN 1A; Charcot Marie Tooth disease type 1A See More

Categories:

Congenital and Genetic Diseases; Nervous System Diseases; RDCRN

Summary Summary

Charcot-Marie-Tooth disease type 1A (CMT1A) is a type of inherited neurological disorder that affects the peripheral nerves. Affected individuals experience weakness and wasting (atrophy) of the muscles of the lower legs beginning in adolescence; later they experience hand weakness and sensory loss. CMT1A is caused by having an extra copy (a duplication) of the PMP22 gene. It is inherited in an autosomal dominant manner. Treatment for this condition may include physical therapy; occupational therapy; braces and other orthopedic devices; orthopedic surgery; and pain medications.^[1]

Last updated: 9/7/2012

Symptoms Symptoms

CMT1 is generally slowly progressive over many years. However, affected individuals often experience long periods without any obvious deterioration or progression.^[2] Occasionally, individuals show accelerated deterioration of function over a few years.^[3] Nerve conduction velocities (NCVs) tend to slow progressively over the first two to six years of life, but they appear to remain relatively stable throughout adulthood.^[2]

Worsening of signs and symptoms tends to be slow in the second to fourth decades of life.^[4] It remains to be confirmed whether, and to what extent, there is clinical and electrophysiological disease progression in affected adults; two studies of adult with CMT1A have shown conflicting results. Authors of one study reported disease progression over time (2–3 years on average), while authors of another study found that both patients and controls (individuals without the condition) had a similar decline of strength and of electrophysiological findings. The findings in the latter study suggested that the decline in adulthood in affected individuals may reflect a process of normal aging rather than on-going active disease.^[5] Any major changes in the pace of progression may warrant consideration of additional acquired, or possibly independently inherited forms, of neuromuscular diseases.^[4]

The severity of signs and symptoms of CMT1A can vary greatly among affected individuals. Individuals who have questions about their own specific signs and symptoms and how they may relate to progression of CMT should speak with their health care provider.

Last updated: 9/7/2012

The Human Phenotype Ontology (HPO) provides the following list of features that have been reported in people with this condition. Much of the information in the HPO comes from Orphanet, a European rare disease database. If available, the list includes a rough estimate of how common a feature is (its frequency). Frequencies are based on a specific study and may not be representative of all studies. You can use the MedlinePlus Medical Dictionary for definitions of the terms below.

Signs and Symptoms	Approximate number of patients (when available)
Areflexia	-
Autosomal dominant inheritance	-
Cold-induced muscle cramps	-
Decreased motor nerve conduction velocity	-
Decreased number of peripheral myelinated nerve fibers	-
Distal amyotrophy	-
Distal muscle weakness	-
Distal sensory impairment	-
Foot dorsiflexor weakness	-
Hammertoe	-
Hearing impairment	-
Heterogeneous	-
Hypertrophic nerve changes	-
Hyporeflexia	-
Insidious onset	-
Juvenile onset	-
Kyphoscoliosis	-
Myelin outfoldings	-
Onion bulb formation	-
Pes cavus	-
Segmental peripheral demyelination/remyelination	-
Slow progression	-
Split hand	-
Steppage gait	-
Ulnar claw	-
Variable expressivity	-

Last updated: 5/8/2017

Inheritance Inheritance

CMT1A is inherited in an autosomal dominant manner.^[6] This means that having a change (mutation) in only one copy of the responsible gene in each cell is enough to cause features of the condition.

In some cases, an affected person inherits the mutated gene from an affected parent. In other cases, the mutation occurs for the first time in a person with no family history of the condition. This is called a de novo mutation.

When a person with a mutation that causes an autosomal dominant condition has children, each child has a 50% (1 in 2) chance to inherit that mutation.

Last updated: 1/10/2017

Treatment Treatment

The resources below provide information about treatment options for this condition. If you have questions about which treatment is right for you, talk to your healthcare professional.

Management Guidelines

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.

Do you have updated information on this condition? Let us know.

Research Research

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

ClinicalTrials.gov lists trials that are studying or have studied Charcot-Marie-Tooth disease type 1A. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.
The Research Portfolio Online Reporting Tool (RePORT) provides access to reports, data, and analyses of research activities at the National Institutes of Health (NIH), including information on NIH expenditures and the results of NIH-supported research. Although these projects may not conduct studies on humans, you may want to contact the investigators to learn more. To search for studies, enter the disease name in the "Text Search" box. Then click "Submit Query".

Patient Registry

The Inherited Neuropathies Consortium is a team of doctors, nurses, research coordinators, and research labs throughout the U.S., working together to improve the lives of people with Charcot Marie Tooth disease through research. The Inherited Neuropathies Consortium has a registry for patients who wish to be contacted about clinical research opportunities.

Organizations Organizations

Nonprofit support and advocacy groups bring together patients, families, medical professionals, and researchers. These groups often raise awareness, provide support, and develop patient-centered information. Many are the driving force behind research for better treatments and possible cures. They can direct people to research, resources, and services. Many groups also have experts who serve as medical advisors. Visit their 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

Charcot-Marie-Tooth Association
PO Box 105
Glenolden, PA 19036
Toll-free: 800-606-2682
Telephone: 610-499-9264
Fax: 610-499-9267
E-mail: info@cmtusa.org
Website: http://www.cmtausa.org/
CMT United Kingdom
3 Groveley Road
Christchurch, Dorset BH23 3HB
United Kingdom
Toll-free: 0800 6526312
Telephone: 01202 474203
E-mail: enquiries@cmt.org.uk
Website: http://www.cmt.org.uk
Hereditary Neuropathy Foundation Inc.
401 Park Avenue, 10th Floor
New York, NY 10016
Toll-free: 855-435-7268
Telephone: 212-722-8396
E-mail: info@hnf-cure.org
Website: http://www.hnf-cure.org/
Muscular Dystrophy Association (MDA)
222 S Riverside Plaza
Suite 1500
Chicago, IL 60606
Toll-free: 800-572-1717
TTY: 1-800-572-1717
E-mail: mda@mdausa.org
Website: http://www.mdausa.org/
Muscular Dystrophy UK
61A Great Suffolk Street
London SE1 0BU
United Kingdom
Telephone: 0800 652 6352; (+44) 0 020 7803 4800
E-mail: info@musculardystrophyuk.org
Website: http://www.musculardystrophyuk.org/

Do you know of an organization? Send us your suggestions.

Living With Living With

Living with a genetic or rare disease can impact the daily lives of patients and families. These resources can help families navigate various aspects of living with a rare disease.

Healthcare Resources

The Muscular Dystrophy Association can help you find a doctor who knows about Charcot-Marie-Tooth disease. Click on the link to search for specialty clinics nearest you.
Services to enhance mobility and independent living are available in each community through the Muscular Dystrophy Association's local network of chapters and field offices. Click here to read more about this service.
The Muscular Dystrophy Campaign provides information regarding the Joseph Patrick Trust which provides financial support for specialist equipment. Click on the link to read more about this trust.

Genetics Resources

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by GeneTests, the American College of Medical Genetics, and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.

Learn More 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

Genetics Home Reference (GHR) contains information on Charcot-Marie-Tooth disease type 1A. This website is maintained by the National Library of Medicine.
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.
MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
The National Institute of Neurological Disorders and Stroke (NINDS) collects and disseminates research information related to neurological disorders. Click on the link to view information on this topic.
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

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.
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 1A. Click on the link to view a sample search on this topic.

Related Diseases Related Diseases

The following diseases are related to Charcot-Marie-Tooth disease type 1A. If you have a question about any of these diseases, you can contact GARD.

GARD Answers GARD Answers

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

My daughter's father was diagnosed with CMT1A in childhood. My daughter is very active and we decided to not have her tested, unless she shows symptoms. I have noticed that her hands sometimes shake. Should this be a concern? Also she walks on her tip toes. She has since she started walking. However I did too as a child and I don't have the disease. Her father has stated that he has never been physically able to walk on his toes even as a child. I read so many things on the internet and it's so confusing. Her feet do not look abnormal. Anyway I was just wondering about the toe walking and the hands shaking sometimes. See answer
Do people with CMT type 1A relapse or does the illness just progress to a more advanced stage? I am aware that it is progressive. I have not read or heard of relapses in this disease, but as it is similar to MS, wondered whether this is a possibility or whether the illness itself is progressing and I will therefore have to learn to accept it. I have experienced periods similar to this but never as extreme. See answer

Have a question? Contact a GARD Information Specialist.

References References

Charcot-Marie-Tooth Disease Fact Sheet. National Institute of Neurological Disorders and Stroke Website. December 11, 2007; http://www.ninds.nih.gov/disorders/charcot_marie_tooth/detail_charcot_marie_tooth.htm. Accessed 2/3/2009.
Thomas D Bird. Charcot-Marie-Tooth Neuropathy Type 1. GeneReviews. August 18, 2011; http://www.ncbi.nlm.nih.gov/books/NBK1205/. Accessed 9/7/2012.
Kliegman. Chapter 605 – Hereditary Motor-Sensory Neuropathies. In: Harvey B. Sarnat. Nelson Textbook of Pediatrics, 19th ed. Philadelphia, PA: Elsevier; 2001;
Francisco de Assis Aquino Gondim. Hereditary Neuropathies of the Charcot-Marie-Tooth Disease Type. Medscape Reference. February 6, 2012; http://emedicine.medscape.com/article/1173484-overview#a1. Accessed 9/7/2012.
Berciano J, Gallardo E, García A, Ramón C, Infante J, Combarros O. Clinical progression in Charcot-Marie-Tooth disease type 1A duplication: clinico-electrophysiological and MRI longitudinal study of a family. J Neurol. October 2010; 257(10):1633-1641.
Thomas D Bird. Charcot-Marie-Tooth Neuropathy Type 1. GeneReviews. March 26, 2015; http://www.ncbi.nlm.nih.gov/books/NBK1205/.