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Last updated:
August 06, 2019
Years published: 1987, 1990, 1999, 2007, 2019
NORD gratefully acknowledges Virginia Casola, MMSc, NORD Editorial Intern from the Emory University Genetic Counseling Training Program and Cecelia A. Bellcross, PhD, MS, CGC, Associate Professor, Director, Genetic Counseling Training Program, Emory University School of Medicine, for assistance in the preparation of this report.
Summary
Dejerine-Sottas syndrome (DSS) is an inherited neurological condition that gradually affects the ability to move. Peripheral nerves are the nerves outside of the brain and spinal cord. These nerves become enlarged or thickened leading to muscle weakness. The condition may progress irregularly and can often be accompanied by pain, weakness, numbness, and a tingling, prickling or burning sensation in the legs. DSS can result in the inability to walk but is not thought to shorten lifespan. This condition does not impact brain function.
Introduction
DSS is a historical name for a type of Charcot-Marie-Tooth disease (CMT3). This terminology was used to describe patients with an early onset form of CMT with a marked breakdown (demyelination) of the protective sheath around the long nerves, exposing and endangering the nerves. The availability of genetic testing has resulted in most types of CMT being renamed based on associations with specific genes, but Dejerine-Sottas syndrome is still sometimes used to describe the condition. DSS has also been described as a type of hereditary motor sensory neuropathy (HMSN3) which are rare genetic nerve disorders that impact movement.
DSS often begins suddenly by age two. Tingling, prickling or burning sensations are usually the first symptoms. Muscle weakness is usually first noticed in the back of the leg. This then spreads to the front leg muscles. Children may have delayed motor milestones, including walking at preschool age or later. Some individuals may need to use a wheelchair by their teenage years. The hand and forearm muscles may become weak as the condition worsens. Individuals with DSS may have respiratory insufficiency, meaning they do not take in enough oxygen or breathe out enough carbon dioxide. Mild vision difficulties may also occur. Other symptoms include pain, loss of heat sensitivity, absence of reflexes, muscle loss (atrophy) of leg muscles, scoliosis (curving of the spine), and ataxia (loss of coordination and balance). Symptoms can vary among individuals diagnosed with DSS.
DSS is caused by changes (mutations) in several different genes. Genes associated with DSS include MPZ, EGR2, PMP22, and PRX. Mutations in these genes can result in the continued loss of myelin (the protective sheath surrounding nerves) leading to muscle weakness and mobility problems. Not all genes associated with DSS have been identified. For about 45% of individuals diagnosed with DSS, the genetic cause of the condition has been determined. This may indicate that other genes not yet identified could also be associated with DSS.
DSS can be inherited in a dominant or recessive manner. Individuals with a dominant form of the condition may have earlier symptom onset compared to individuals with the recessive form.
Dominant genetic disorders occur when only a single copy of a non-working gene is necessary to cause a particular disease. The non-working gene can be inherited from either parent or can be the result of a mutated (changed) gene in the affected individual. The risk of passing the non-working gene from an affected parent to an offspring is 50% for each pregnancy. The risk is the same for males and females.
Recessive genetic disorders occur when an individual inherits a non-working gene from each parent. If an individual receives one working gene and one non-working gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the non-working gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier, like the parents, is 50% with each pregnancy. The chance for a child to receive working genes from both parents is 25%. The risk is the same for males and females.
Dejerine-Sottas syndrome often begins by age two. This disorder is thought to affect males and females equally. It can affect people from all races and ethnicities.
Diagnosis of DSS can be made through genetic testing or based on symptoms and disease severity. Criteria for a clinical diagnosis include:
Treatment
There is no cure for DSS. Treatment is supportive and aimed at reducing symptoms. Individuals may see a team of neurologists, physiatrists, orthopedic surgeons (specialists trained in surgery of the musculoskeletal system), and physical and occupational therapists. Ankle or foot surgery or special shoes with good ankle support can help correct or stabilize joints involved with walking. Muscle pain can be treated with acetaminophen or nonsteroidal anti-inflammatory medications. Nerve pain can be treated with tricyclic antidepressants or other medications such as carbamazepine or gabapentin. It is important to work with a doctor to identify the type of pain, so the best medication can be prescribed. Certain medications should not be taken if an individual is diagnosed with DSS.
Some organizations offer assistance to individuals with vision or mobility difficulties and their families. Genetic counseling may be helpful for families and individuals diagnosed with DSS.
Information on current clinical trials is posted on the Internet at https://clinicaltrials.gov/ All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov
Some current clinical trials also are posted on the following page on the NORD website: https://rarediseases.org/living-with-a-rare-disease/find-clinical-trials/
For information about clinical trials sponsored by private sources, contact: https://www.centerwatch.com/
For information about clinical trials conducted in Europe, contact: https://www.clinicaltrialsregister.eu/
JOURNAL ARTICLES
Hobbelink SMR, et al., Dejerine–Sottas disease in childhood—Genetic and sonographic heterogeneity. Brain and Behavior. 2018;8:1-8.
Mathis S, Vallar JM. Jules Dejerine and the peripheral nervous system. Neurology. 2017;89:611–615.
Baets J, et al, Genetic spectrum of heredity neuropathies with onset in the first year of life. Brain. 2011;134;2664-2676.
Pareyson D, Differential diagnosis of Charcot-Marie-Tooth disease and related neuropathies. Neurol Sci. 2004;25;72-82.
Reilly MM, Genetically determined neuropathies. J Neurol. 1998;245:6-13.
Vasilescu C, Hereditary motor and sensory neuropathy. Clinical, genetic and electrophysiological studies. Rom J Neurol Psychiatry. 1993;31:207-219.
Kouvaras G, et al., Hypertrophic peripheral neuropathy (Dejerine-Sottas disease) associated with heart block. Case report presentation and review of the literature. Jpn Heart J. 1990;31:404-410.
Mitchell GW, Response to immunosuppressive therapy in patients with hereditary motor and sensory neuropathy and associated dysimmune neuromuscular disorders. Eur Neurol. 1987;27:188-196.
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