Thevenard Syndrome

Overview

Thevenard syndrome, also known as Thevenard’s disease or hereditary sensory and autonomic neuropathy type I (HSAN I), is a rare genetic neurological disorder primarily affecting the sensory and autonomic nerves. The condition is characterized by a progressive loss of pain and temperature sensation, especially in the lower extremities, leading to chronic ulcerations, infections, and, in severe cases, spontaneous amputations. Thevenard syndrome typically presents during adolescence or early adulthood and follows an autosomal dominant inheritance pattern. It is a slowly progressive disorder and part of a broader group of hereditary sensory and autonomic neuropathies (HSAN).

Causes

Thevenard syndrome is caused by mutations in genes responsible for the normal function and maintenance of sensory and autonomic neurons. In most cases, it is associated with mutations in the SPTLC1 gene, which encodes a subunit of the enzyme serine palmitoyltransferase. This enzyme is involved in the biosynthesis of sphingolipids, essential components of nerve cell membranes. Disruption of this pathway leads to degeneration of sensory nerves.

The condition is inherited in an autosomal dominant manner, meaning that a single copy of the mutated gene from one parent is sufficient to cause the disorder. A family history of similar symptoms is commonly present, although spontaneous mutations can occur.

Symptoms

The symptoms of Thevenard syndrome primarily affect the sensory nervous system, although some autonomic symptoms may be present. The hallmark features usually develop during the second or third decade of life and include:

Sensory Symptoms:

• Loss of pain and temperature sensation – Most pronounced in the feet and lower legs, progressing proximally over time.

• Painless injuries – Due to inability to feel trauma, leading to unnoticed wounds or burns.

• Chronic foot ulcers – Resulting from repeated trauma and poor wound healing.

• Infections and osteomyelitis – Infections of soft tissues and bones are common due to poor sensation and wound care.

• Spontaneous amputations – In severe cases, repeated infections and necrosis can lead to loss of digits or limbs.

Autonomic and Other Features:

• Decreased sweating (anhidrosis)

• Thickened or discolored skin over affected areas

• Muscle wasting in distal limbs – May occur due to nerve degeneration.

• Delayed wound healing

Unlike some other forms of HSAN, motor function and intellectual development are generally preserved in Thevenard syndrome.

Diagnosis

Diagnosis of Thevenard syndrome is based on clinical evaluation, family history, and confirmatory genetic testing. Diagnostic steps may include:

• Neurological examination – Identifies sensory loss, particularly for pain and temperature.

• Nerve conduction studies (NCS) and electromyography (EMG) – Show reduced or absent sensory nerve action potentials, with relatively preserved motor function.

• Skin or nerve biopsy – May reveal loss of unmyelinated and small myelinated fibers.

• Genetic testing – Confirms mutations in the SPTLC1 gene or other associated genes to establish a definitive diagnosis.

• Laboratory tests – May be done to rule out other causes of peripheral neuropathy, such as diabetes or vitamin deficiencies.

Early diagnosis is important to prevent complications through proactive wound care and injury prevention strategies.

Treatment

There is currently no cure for Thevenard syndrome. Treatment is symptomatic and focuses on preventing complications, managing infections, and preserving limb function. A multidisciplinary team approach is often necessary. Treatment options include:

1. Wound and Infection Management:

• Regular foot inspections – To detect injuries early.

• Wound care – Use of dressings, topical antibiotics, and debridement for ulcers.

• Systemic antibiotics – For treatment of deep or bone infections (osteomyelitis).

2. Protective Measures:

• Protective footwear – To prevent trauma to insensitive feet.

• Orthopedic devices – Bracing or offloading devices may reduce pressure on ulcerated areas.

3. Pain and Sensory Management:

• In some individuals with residual neuropathic pain, medications such as gabapentin or pregabalin may be considered, although pain is often absent due to sensory loss.

4. Surgical Intervention:

• In advanced cases with non-healing infections or gangrene, surgical debridement or amputation may be necessary.

5. Genetic Counseling:

• Offered to families affected by the condition to discuss inheritance patterns, recurrence risk, and prenatal diagnosis options.

Prognosis

The prognosis for individuals with Thevenard syndrome varies depending on the severity of sensory loss and the effectiveness of wound management. Key points include:

• Normal lifespan – If complications like severe infections are managed well, life expectancy is generally normal.

• Progressive nature – Symptoms tend to worsen over time, and complications can accumulate, especially without preventive care.

• Risk of disability – Recurrent infections, ulcers, and amputations can lead to significant physical disability if not managed aggressively.

• Quality of life – Can be maintained with diligent care, assistive devices, and education about foot care and injury prevention.

Although Thevenard syndrome is rare and challenging to manage, early diagnosis, patient education, and coordinated care can significantly reduce morbidity and enhance long-term outcomes.