Overview

Dejerine-Sottas Syndrome (DSS) is a condition that impacts the nerves outside the brain and spinal cord (peripheral nerves), causing progressive weakness and sensory problems.¹ The syndrome is diagnosed in early childhood and is inherited by a child from their parents.

Inheritance patterns of DSS can follow two types: autosomal dominant or autosomal recessive. Understanding how this condition is inherited is essential for families that may be at risk and how that may impact family planning.

Causes

In the body, genes are responsible for coding different parts that make up the body, e.g. hair and eye colour. This is no different for peripheral nerves, which are structures that connect different body parts by sending messages in the form of nerve impulses.² Specifically, there are different genes that encode different parts of the peripheral nerves, such as the myelin sheath, which is the protective layer of nerves. Under normal circumstances, genes such as PMP22, MPZ, EGR2 and PRX are responsible for encoding the myelin sheath, aiding the formation of the peripheral nerves.³ However, people with DSS have this function disrupted, leading to the myelin sheath being made incorrectly, reducing the function of the peripheral nerves. The reason for this disruption is caused by a change within the genes (mutation) that encode the myelin sheath, preventing the genes from working properly.

Often, mutations can either happen sporadically or be inherited from your parents. Each person has two copies of genes, one from each parent, which are inherited and determine how certain features in your body are encoded. DSS inheritance is dependent on two different types of inheritance patterns: autosomal dominant and autosomal recessive.⁴ Autosomal refers to a gene that isn’t on a sex chromosome, so it isn’t involved in encoding gender-based features and thus impacts both those assigned male or female at birth equally. Thus, if a person were to be autosomal dominant for DSS, this means that they have inherited one copy of the altered gene from their parent, which is enough for them to get the condition. In addition to that, autosomal recessive individuals will have inherited two altered genes from both parents, resulting in them developing DSS.

Inheritance patterns

It's essential to further delve into how these inheritance patterns work and the chances of a child getting DSS, depending on their parents' genes.

Autosomal dominant inheritance

• This means that a child has a 50 per cent chance of inheriting DSS if one parent has the altered gene, and this parent will have DSS⁵
• Often linked to new mutations and may not be inherited from their parent, but occur spontaneously 
• Symptoms may vary in severity, even within the same family

Autosomal recessive inheritance

• This means both parents carry one copy of the altered gene, but do not have DSS
• A child has a 25 per cent chance of being affected, a 50 per cent chance of being a carrier and a 25 per cent chance of inheriting no altered gene⁵
• Recessive cases often present earlier and more severely 

Symptoms 

Symptoms often appear during infancy or early childhood, especially if the inheritance was autosomal recessive. There are many signs that could indicate DSS; the following are the main signs:

• Progressive muscle weakness, particularly in the legs and feet
• Loss of sensation in the extremities (toes and fingers)
• Foot deformities, e.g. high arched feet 

DSS progression may be slower in autosomal dominant forms and more rapid/severe in recessive forms.

Diagnosis

DSS is typically diagnosed in early childhood, when delays in walking, unusual gait patterns, or weakness in the legs become noticeable. Diagnosis is based on a combination of clinical assessment, specialised tests, and genetic analysis.

Diagnosis will begin with the doctor taking a detailed medical history, including questions about symptoms, when they started, and whether other family members are affected. A physical examination may also be done to look at muscle strength, reflexes, coordination, and sensation in the arms and legs.

Moreover, nerve conduction studies are often used to measure how quickly electrical signals travel along the nerves.⁶ In DSS, these signals are much slower than normal because the protective coating around the nerves is damaged. Alongside this, electromyography, which records electrical activity in the muscles, may also be carried out to confirm the pattern of weakness.

Magnetic resonance imaging (MRI) scans can sometimes be done to reveal thickened peripheral nerves. Although this finding is not unique to DSS, it can help support the diagnosis.

Despite this, the most reliable way to confirm the condition is through genetic testing. A blood sample is analysed to check for changes in the genes most commonly associated with the syndrome. Identifying the genetic change can help determine whether the condition is inherited in an autosomal dominant or autosomal recessive pattern. This information is important for family planning and for identifying other relatives who may be at risk.

Once a diagnosis is made, ongoing follow-up is recommended to monitor progression and to guide treatment and support.

Treatment and management

At present, there is no cure for DSS; current treatment focuses on reducing symptoms, slowing progression, and maintaining quality of life. Care is usually coordinated by a multidisciplinary team that may include neurologists, physiotherapists, occupational therapists, orthopaedic specialists, and sometimes psychologists.

The main form of treatment is through physiotherapy, where regular, tailored exercises can help preserve muscle strength and flexibility, reduce stiffness, and prevent long-term joint problems. Stretching programmes are also especially useful in avoiding contractures, while strengthening exercises help maintain independence in walking and balance.

Occupational therapy could also be provided to support day-to-day living. Therapists may suggest practical strategies for household tasks and recommend adaptive equipment such as splints, modified cutlery, or specialist computer keyboards.⁷ These interventions help people remain independent for as long as possible.

Orthopaedic care is often needed to address foot deformities like high arches or curled toes. Braces, orthotic insoles, and specially designed shoes can improve stability and comfort. In more severe cases, corrective surgery may be advised.

Additionally, pain is a problem for some people with DSS. The pain usually reported is neuropathic, caused by damaged nerves, and can be treated with specific medicines such as gabapentin or pregabalin. For milder symptoms, over-the-counter medicines may be sufficient. In cases where pain is persistent, referral to a pain management clinic may be helpful.

Mobility aids are sometimes required as the condition progresses. These may include walking sticks, crutches, or wheelchairs. Choosing the right aid depends on individual needs and should be guided by physiotherapists and occupational therapists.

Although no approved cure exists, research is ongoing into gene therapy and new drug treatments that may one day target the underlying cause of the condition.

Living with the condition

Living with DSS can present both physical and emotional challenges. The condition is progressive, which means that symptoms generally worsen over time. However, with appropriate support, many people maintain independence and adapt successfully to changes in mobility.

For some people with DSS, daily activities can become more difficult as weakness in the hands and feet increases. To combat this, adaptive equipment and home modifications can help, such as stair lifts, grab rails, and specialised kitchen tools. Planning for these adjustments early can make transitions smoother.

In addition to that, emotional well-being is an important part of care when living with DSS. A diagnosis of DSS can be difficult for both patients and families, particularly when it is made in childhood, so it's essential to have the necessary support systems in place. Counselling and peer support groups provide opportunities to share experiences and coping strategies.

Children with DSS may need extra support and adjustments whilst at school.  In schools, teachers and staff can work with healthcare professionals to provide accommodations such as extra time for physical tasks, accessible classrooms, and the use of laptops or tablets if handwriting is difficult. Moreover, adults with DSS may require workplace adjustments, which can include ergonomic seating, voice-recognition software, or flexible working arrangements, to provide comfort in their working environment. 

Support and further information

DSS is rare, so it's common to feel isolated after diagnosis. Several organisations provide information, support, and opportunities to connect with others:

• Charcot–Marie–Tooth UK, which offers advice and community support for people with inherited neuropathies
• Muscular Dystrophy UK, which provides resources and advocacy for a range of neuromuscular conditions
• Genetic Alliance UK, which represents families with rare genetic conditions and campaigns for better services
• NHS Rare Genetic Conditions Services, which provide specialist care and advice through referral from a GP or hospital doctor

These organisations can help families find practical advice on living with the condition, updates on research, and access to local support networks.

Summary

Dejerine–Sottas syndrome (DSS) is a rare inherited condition that affects the peripheral nerves. It can be inherited in autosomal dominant or autosomal recessive patterns and usually appears in childhood with weakness, loss of sensation, and problems with walking. Diagnosis is based on clinical examination, nerve studies, scans, and genetic testing. There is no cure, but physiotherapy, occupational therapy, orthopaedic support, pain management, and mobility aids can all help maintain quality of life. Moreover, families may benefit from genetic counselling and support groups to aid in living with DSS. It’s essential that anyone worried about symptoms or with a family history should seek medical advice for guidance and ongoing care.