Dejerine-Sottas syndrome (DSS) is an inherited neurological condition that gradually affects the ability to move. Peripheral nerves are the nerves outside 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 lead to the inability to walk, but is not thought to shorten life expectancy. The condition does not affect brain function [1].

DSS is a historical name for a type of Charcot-Marie-Tooth disease (CMT3). The term was used to describe patients with an early form of CMT with a marked breakdown (demyelination) of the protective sheath around long nerves, which exposes and compromises the nerves. The availability of genetic testing has led to the renaming of most types of CMT based on their association 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 sensorimotor neuropathy (HMSN3), a rare genetic neurological disorder that affects movement [1].

Figure 1: Schematic of the structure of a nerve cell [1].

DSS often begins suddenly around the age of two. Tingling, tingling, or burning sensations are usually the first symptoms. Muscle weakness is usually first seen in the back of the leg. It then spreads to the muscles in the front of the leg. Children may have delayed motor milestones, including walking, in preschool or later. Some people may need to use a wheelchair in their teens. Muscles in the hands and forearms may weaken as the condition worsens. People with DSS may have respiratory failure, meaning they do not get enough oxygen or get enough carbon dioxide out. Mild vision problems may also occur. Other symptoms include pain, loss of sensitivity to heat, lack of reflexes, loss of muscle (atrophy) of the leg muscles, scoliosis (curvature of the spine), and ataxia (loss of coordination and balance). Symptoms may vary among people diagnosed with DSS [1].

Figure 2: Radiological image of skeletal abnormalities of the legs in Dejerine-Sattas syndrome [1].

DSS is caused by changes (mutations) in several different genes. The genes associated with DSS include the MPZ gene, located on the long arm of chromosome 1 at 1q23.3, the EGR2 gene, located on the long arm of chromosome 10 at 10q21.3, the PMP22 gene, located on the short arm of chromosome 17 at 17p12, and the PRX gene, located on the long arm of chromosome 19 at 19q13.2. Mutations in these genes can lead to the progressive loss of myelin (the protective sheath around nerves), which leads to muscle weakness and movement problems. Not all genes associated with DSS have been identified. For about 45 percent of people with DSS, a genetic cause of the condition has been identified. This may indicate that other genes that have not yet been identified could also be associated with DSS [1,2].

Figure 3: Schematic of the structure of MPZ, PMP22, and Cx32 proteins [1].

DSS can be inherited as a dominant or recessive trait. People with the dominant form of the condition may have earlier onset of symptoms than people with the recessive form. Dominant genetic disorders occur when only one copy of an inactive gene is needed to cause a particular condition. The inactive gene can be inherited from either parent or can be the result of a mutated (changed) gene in the affected person. The risk of passing on the inactive gene from an affected parent to a child is 50 percent for each pregnancy. This risk is the same for men and women. Recessive genetic disorders occur when a person inherits one inactive gene from each parent. If a person receives one active gene and one inactive gene for the condition, the person will be a carrier of the condition, but usually will not show symptoms. The risk of two carrier parents passing on both of the faulty genes and having an affected child is 25 percent with each pregnancy. The risk of having a carrier child like the parent is 50 percent with each pregnancy. The chance of a child receiving active genes from both parents is 25 percent. This risk is the same for men and women [1,2].

Dejerine-Sottas syndrome often begins around the age of two. The disorder is thought to affect males and females equally. It can affect people of all races and ethnicities [1,3].

Charcot-Marie-Tooth disease (CMT) is a group of disorders in which the peripheral motor and sensory nerves are affected, leading to muscle weakness and atrophy, as well as loss of sensation. The nerves in the feet, legs, and sometimes the hands are affected. Hereditary sensory radicular neuropathy is a dominantly inherited disorder that is initially characterized by pain and loss of temperature sensation in the feet and legs. Later, attacks of severe pain throughout the body may occur, along with muscle weakness and ulcers on the toes [1,3].

Figure 4: Schematic of the biochemical mechanism of MPZ, PMP22, Cx32, and L-Periaxin genes in Schwann neurons [1].

The diagnosis of DSS can be made through genetic testing or based on symptoms and severity of the disease. Clinical diagnostic criteria include: symptoms beginning by age two and delayed motor milestones, severe motor and sensory deficits, severely reduced motor nerve conduction velocity (the speed of nerve transmission), and nerve biopsy showing loss of myelin [1,4].Figure 5: Pie chart of MPZ gene mutation frequency in the world's major population countries [1].

There is no cure for DSS. Treatment is supportive and aimed at reducing symptoms. People may see a team that includes neurologists, physiatrists, orthopedic surgeons (specialists trained in musculoskeletal surgery), and physical and occupational therapists. Ankle or foot surgery or special shoes with good ankle support can help correct or stabilize the joints involved in walking [1,5].

Figure 6: Schematic of the physical map of chromosome number 10, where the EGR2 gene is located on the long arm of this chromosome as 10q21.3 [1].

Muscle pain can be treated with acetaminophen or nonsteroidal anti-inflammatory drugs. Nerve pain can be treated with tricyclic antidepressants or other medications, such as carbamazepine or gabapentin. It is important to work with your doctor to identify the type of pain so that the best medication can be prescribed. Some medications should not be taken if you have been diagnosed with DSS. Some organizations help people with vision or movement problems and their families. Genetic counseling may be helpful for families and people with DSS [1,5].

Figure 7: Schematic of the autosomal dominant (left) and autosomal recessive (right) inheritance patterns that Dejerine-Sattas syndrome follows [1].

DSS often begins suddenly around the age of two. Tingling, tingling, or burning sensations are usually the first symptoms. Muscle weakness is usually first seen in the back of the leg. It then spreads to the muscles in the front of the leg. Children may have delayed motor milestones, including walking, in preschool or later. Some people may need to use a wheelchair in their teens. Muscles in the hands and forearms may weaken as the condition worsens. People with DSS may have respiratory failure, meaning they do not get enough oxygen or get enough carbon dioxide out. Mild vision problems may also occur. DSS can be inherited as a dominant or recessive trait. People with the dominant form of the condition may have earlier onset of symptoms than people with the recessive form. Dominant genetic disorders occur when only one copy of an inactive gene is needed to cause a particular condition. The inactive gene can be inherited from either parent or can be the result of a mutated (changed) gene in the affected person. The risk of passing on the inactive gene from an affected parent to a child is 50 percent for each pregnancy. Charcot-Marie-Tooth disease (CMT) is a group of disorders in which the peripheral motor and sensory nerves are affected, leading to muscle weakness and atrophy, as well as loss of sensation. The nerves in the feet, legs, and sometimes the hands are affected. Hereditary sensory radicular neuropathy is a dominantly inherited disorder that is initially characterized by pain and loss of temperature sensation in the feet and legs. There is no cure for DSS. Treatment is supportive and aimed at reducing symptoms. Muscle pain can be treated with acetaminophen or nonsteroidal anti-inflammatory drugs. Nerve pain can be treated with tricyclic antidepressants or other medications, such as carbamazepine or gabapentin [1-5].

1. Asadi S. Pathology in Medical Genetic Books. Amidi Publications. 2025; 21.
2. Hobbelink SMR, Brockley CR, Kennedy RA, Carroll K, Valle K, Rao P, et al. Dejerine–Sottas disease in childhood Genetic and sonographic heterogeneity. Brain and Behavior. 2018; 8: 1-8.
3. Mathis S, Vallar JM. Jules Dejerine and the peripheral nervous system. Neurology. 2017; 89: 611-615.
4. Baets J, Deconinck T, Vriendt ED, Zimon M, Yperzeele L, Hoorenbeeck KV, et al, Genetic spectrum of heredity neuropathies with onset in the first year of life. Brain. 2011; 134; 2664-2676.
5. Pareyson D. Differential diagnosis of Charcot-Marie-Tooth disease and related neuropathies. Neurol Sci. 2004; 25: 72-82.