Introduction

If you want to know more about Dejerine Sottas syndrome, then you’re in the right place. Understanding this syndrome is crucial for improving patient outcomes, ensuring that affected individuals receive appropriate care from the earliest stages of life.

Dejerine Sottas syndrome (DSS) is an inherited, rare disorder. It is commonly linked to mutations in PMP22, MPZ, and EGR2 genes.¹ Its early-onset peripheral neuropathy presents itself in infancy or early childhood with clinical features being distinctive and significant. 

DSS manifests itself with delayed motor milestones, hypotonia, muscle weakness, sensory loss and electrophysiological patterns. Recognising these symptoms is critical for a timely diagnosis and effective management planning. This article examines these clinical features to provide a clear and confident overview for accurate clinical recognition and management.

What is the pathophysiology of DSS?

This syndrome is a demyelinating peripheral neuropathy (whereby the myelin sheath that protects nerves becomes damaged) affecting mobility over time. These peripheral nerves may become enlarged, leading to muscle weakness,pain, numbness, and a tingling and burning sensation in the legs. The severe impairment of both sensory and motor neurones due to demyelination can heavily reduce nerve conduction velocities to below 12ms-1.²

Symptoms typically begin to manifest early in life, often before the age of three, with tingling sensations often being the first symptoms. Affected infants can present themselves with hypotonia and delayed motor responses such as sitting and standing. This condition can be progressive with deterioration in strength and coordination continuing into childhood and contributing to disability by adolescence.

DSS can be inherited through both an autosomal dominant and recessive manner and is caused by mutations in different genes such as MPZ, EGR2, PRX and PMP22.¹ This can result in continued loss of myelin leading to mobility issues.

What are the symptoms of this syndrome?

There can be a range of different symptoms:³

Motor symptoms:

• Delayed motor milestones such as sitting and standing
• Hypotonia
• Muscle atrophy in hands and feet
• Reduced muscle strength in the hands
• Muscle weakness
• Absence of reflexes

Sensory symptoms:

• Impaired vibration, proprioception and light touch sensation
• Impaired balance

Skeletal and orthopaedic symptoms:

• Pes cavus (stiff high-arched foot)
• Scoliosis

Other symptoms include impaired vision and the loss of heat sensitivity. However, symptoms can vary between individuals diagnosed with DSS.

What is the prognosis of this disease?

The prognosis of this syndrome generally reflects a severe and progressive neuropathy beginning in childhood. Many patients will experience severe motor and sensory disability within the first decade of their life, with some becoming wheelchair dependent by adolescence. 

However, the rate of this progression will depend on the specific mutation, with certain variants linked to a slower decline in function. Life expectancy is not usually reduced but a patient's quality of life can be affected due to mobility limitations, orthopaedic complications, and reduced independence.  Despite this, with appropriate management such as physiotherapy, the patient can reduce further complications and maintain their functional abilities.

How is DSS diagnosed?

Diagnosis is usually confirmed with a family history, early onset of symptoms as well as nerve conduction tests. Genetic testing can also be used for diagnosis. 

Patient history and a neurological examination will reveal motor delay, hypotonia, and sensory loss.

Nerve conduction velocity (NCV) tests, nerve biopsies, electromyography (EMG), and brain MRI are also crucial in differentiating this syndrome from other diseases. NCV tests from those diagnosed with DSS usually reveal nerve velocities less than 15m/s,which is significantly slower compared to those without DSS. Biopsies will show axonal loss and demyelination as well as onion bulb formations. 

Definitive confirmation is achieved through genetic testing, with the identification of variants in the genes mentioned above.⁴

Thus, early and accurate diagnosis is crucial in estimating prognosis and informing genetic counselling to ensure this syndrome is managed effectively.

How is DSS treated?

There is currently no cure for this syndrome. Treatment is aimed at managing symptoms, preserving function, preventing complications and improving patient’s quality of life. A team of neurologists, physiotherapists, and orthopaedic surgeons are all involved in managing the patient’s symptoms.

Early intervention with physiotherapy is greatly important in joint flexibility and mobility with treatment focussing on:

• Promoting muscle strength
• Maintaining healthy positions of the joints
• Improving the patient’s gait to reduce the fall of risks
• Managing pain
• Promoting independence

Orthotic devices such as ankle foot orthoses can be used to improve gait. Alongside this, ankle or foot surgery or even shoes with good ankle support can help with stabilising joints involved in walking. 

Surgical interventions can also be used to address severe foot deformities or even problems associated with the spine such as scoliosis. Muscle pain can additionally be treated with medications, but it is important that this is consulted with a doctor. 

Additionally, genetic counselling can also provide families with information about inheritance patterns and the risk of reoccurrence. Ongoing research into repairing myelin and gene targeted therapies bring hope for disease modifying treatments in DSS.

Summary

Dejerine Sottas syndrome is a rare but clinically distinctive neuromuscular disorder that requires prompt recognition. The combination of symptoms such as hypotonia, delayed motor milestones, muscle weakness, and sensory loss significantly impact a patient’s quality of life. DSS is commonly revealed by a reduced nerve conduction velocity. However, the presence of DSS can be more accurately diagnosed via genetic testing. 

Although there is no cure, early identification allows for supportive therapy which can preserve mobility and limit complications, which can enhance the patient’s quality of life. Multidisciplinary support such as physiotherapy, orthopaedic interventions, and genetic counselling are essential in ensuring effective management for the patient. Thus, understanding this syndrome is essential in improving the long term outcomes for patients with this disease.

FAQs

At what age do symptoms typically begin?

Symptoms typically begin in infancy or early childhood such as the age of two.

Is DSS life threatening?

Life expectancy is typically normal, yet mobility and independence can be affected.

Is DSS inherited?

Yes, it can be inherited in an autosomal dominant and recessive manner, depending on the specific mutation.

Is there research being done on new treatments?

Yes, there is new research exploring gene therapies, myelin repair strategies and disease modifying drugs.