Diagnosis and Testing
Obtaining a definitive genetic diagnosis is an important first step in seeking appropriate care and treatment, learning about potential research or therapies that may become available, and preparing for the future. Patients and their families should consider discussing the implications of obtaining a diagnosis of A rare inherited peripheral neuropathy often characterized by rapidly progressive, asymmetrical upper and lower extremity weakness, muscle atrophy leading to handicap, and respiratory issues with no available treatment. CMT4J is a recessive subtype of CMT caused by a variant, also referred to as a mutation, in the FIG4 gene. with their physician and a genetic counselor or other specialists who are familiar with the disease management of CMT4J.
Because of low disease awareness and the fact that neurological symptoms are among the earliest signs observed, common misdiagnoses may include A neurological disorder characterized by progressive weakness and impaired sensory function. It is considered the chronic counterpart of the acute disease Guillain-Barré Syndrome. CIDP is the most common misdiagnosis for patients living with CMT4J., A neurological disease that disrupts communication between the brain and other parts of the body. Multiple sclerosis is characterized by muscle weakness and difficulty with coordination and balance, so some individuals living with CMT4J are first misdiagnosed with MS., A rare neurological disorder in which the body’s immune system mistakenly attacks part of its peripheral nervous system. GBS presents similar signs and symptoms to CMT4J, including muscle weakness., A group of rare neurological disorders known as motor neuron diseases. ALS is characterized by the progressive degeneration and eventual death of nerve cells in the brain, brainstem, and spinal cord. ALS presents similar signs and symptoms to CMT4J and is often referred to as Lou Gehrig’s disease., and other neuromuscular disorders.
If you believe your child is showing signs or symptoms of CMT4J, tests are available for a physician or other healthcare professional to order to help confirm a diagnosis.
Testing for CMT4J may not be included in standard testing panels; however, a diagnostic genetic test including an expanded exome sequencing panel for CMT4J can be requested to confirm a diagnosis. Many academic and commercial laboratories offer genetic blood testing. Your physician can help you navigate the process or refer you to a geneticist.
A representative is available to help you by calling 1-877-237-5020 or via email at firstname.lastname@example.org.
A Researcher’s Perspective on Diagnosis:
“CMT4J is difficult to diagnose without genetic testing because it looks very similar to other neuromuscular illnesses. If you are noticing common symptoms related to muscle weakness and wasting affecting the feet and legs, and overwhelming fatigue, it is important to document these symptoms and discuss with your primary care doctor or request a referral to a neurologist. Your healthcare provider will be able to review your symptoms and order a saliva or blood DNA test. With a positive diagnosis, you or a family member may be eligible to participate in research that could help the community better understand CMT4J.”
Mario Saporta, M.D., Ph.D., is an Assistant Professor of Neurology and Human Genetics at the The most common inherited motor and sensory neuropathies, composed of a group of pathologically and genetically distinct subtypes ranging from slowly to rapidly progressive disease. CMT is further classified based on the genetic mutation or variant involved – for instance, CMT4A, CMT4B, etc. Center of Excellence at the University of Miami. In addition to his role as a primary care physician, Dr. Saporta’s research and clinical work is focused on neurogenetic and neuromuscular conditions, particularly inherited peripheral neuropathies.
- Nicholson, G., Lenk, G. M., Reddel, S. W., Grant, A. E., Towne, C. F., Ferguson, C. J., … Meisler, M. H. (2011). Distinctive genetic and clinical features of CMT4J: a severe Nerve problem that causes pain, numbness, tingling, swelling, or muscle weakness in various parts of the body typically beginning in the hands or feet, then getting worse over time. caused by A mutation is any inherited genetic change. The term “mutation” is being replaced by the term “variant.” in the PI(3,5)P₂ phosphatase The FIG4 gene is the only gene in which pathogenic variants are known to cause CMT4J.. Brain: a journal of neurology, 134(Pt 7), 1959–1971. doi:10.1093/brain/awr148. Retrieved June 26, 2019, from link.
- Field research conducted by Neurogene and Ten Bridge Communications, July 2019.
- Hu, B., McCollum, M., Arpag, S., Moiseev, D., Castoro, R., Burnette, B., Siskind, C., Day, J., Yawn, R., Feely, S., Yan Q., Shy., M., Li, J. (2018). A soft white material that forms a thick layer around the axons of some neurons and is composed chiefly of lipids (such as cerebroside and cholesterol), water, and smaller amounts of protein. abnormality in Charcot-Marie-Tooth type 4J recapitulates features of acquired demyelination. Annals of Neurology. 83(4), 756-70. Retrieved September 12, 2019, from link.
- Vaccari, I., Carbone, A., Previtali, S. C., Mironova, Y. A., Alberizzi, V., Noseda, R., Rivellini, C., Bianchi, F., Del Carro, U., D’Antonio, M., Lenk, G. M., Wrabetz, L., Giger, R. J., Meisler, M. H., Bolino, A. (2015, Jan. 15). Loss of Fig4 in both Schwann cells and motor A nerve cell that receives and sends electrical signals from sensory cells and other neurons over long distances within the body. These signals are sent to muscle neurons and other neurons. contributes to CMT4J neuropathy. Human Molecular Genetics. 24(2), 383-96. Retrieved September 12, 2019, from link.
- Martyn, C., & Li, J. (2013, Feb.). Fig4 Deficiency: a newly emerged lysosomal storage disorder? Progress in Neurobiology. doi:10.1016/j.pneurobio.2012.11.001. Retrieved September 12, 2019, from link.
- Rajabelly, Y., Adams, D., Latour, P., Attarian, S. (2016, March 23). Hereditary and inflammatory neuropathies: a review of reported associations, mimics, and misdiagnoses. JNNP Online First. BMJ. doi:10.1136/jnnp-2015-310835. Retrieved September 12, 2019, from link.
- Zhang X., Chow C. Y., Sahenk Z., Shy, M. E., Meisler, M. H., Li, J. (2008, Aug.). Mutation of FIG4 causes a rapidly progressive, asymmetric neuronal degeneration. Brain. 131(8), 1990–2001. Retrieved September 12, 2019, from link.