Roussy–Lévy syndrome

Overview

Roussy–Lévy syndrome (RLS) is a rare, inherited neurological disorder classified as a subtype of Charcot–Marie–Tooth disease (CMT), specifically affecting the peripheral nerves. It is characterized by progressive muscle weakness and atrophy, sensory deficits, areflexia (loss of deep tendon reflexes), and a distinctive gait abnormality known as a “sensory ataxia.” The condition was first described by neurologists Gustave Roussy and Gabrielle Lévy in the 1920s.

Roussy–Lévy syndrome shares many features with CMT type 1, but also includes tremor and balance issues due to proprioceptive loss. Symptoms often begin in childhood or adolescence and progress slowly over time. Though not life-threatening, RLS can lead to significant disability, especially related to mobility and fine motor coordination.

Causes

Roussy–Lévy syndrome is caused by mutations in genes that affect the structure and function of myelin—the insulating layer that surrounds nerves and ensures efficient electrical signaling. The most commonly implicated genes are:

Genetic Mutations Associated with RLS:

• PMP22 (Peripheral Myelin Protein 22): Most often duplicated or mutated, also involved in CMT1A

• MPZ (Myelin Protein Zero): Encodes a key structural component of myelin

Inheritance Pattern:

• Autosomal dominant inheritance: A single copy of the mutated gene is sufficient to cause the disorder

• In some cases, the condition may arise due to a new (de novo) mutation with no family history

Symptoms

Symptoms of Roussy–Lévy syndrome typically begin in early childhood or adolescence and are progressive. The hallmark features involve sensory and motor deficits in the peripheral nervous system, leading to coordination problems and muscle wasting.

Key Clinical Features:

• Distal muscle weakness and atrophy: Especially in the legs and feet, leading to foot drop

• Sensory ataxia: Impaired sense of position and vibration resulting in unsteady gait and poor coordination

• Areflexia: Loss or reduction of deep tendon reflexes, especially at the ankles and knees

• Tremor: Fine tremors in the hands or limbs, particularly during movement (intention tremor)

• Pes cavus (high-arched feet): Common orthopedic abnormality in hereditary neuropathies

Additional Possible Features:

• Toe walking or frequent falls in children

• Hand muscle weakness affecting grip and fine motor skills

• Leg cramps or muscle fatigue during exertion

• Scoliosis (spinal curvature) in some individuals

Diagnosis

Diagnosis of Roussy–Lévy syndrome involves clinical examination, family history, electrophysiological studies, and genetic testing. Due to its overlap with other types of Charcot–Marie–Tooth disease, accurate diagnosis requires a combination of tests and specialist evaluation.

Clinical Evaluation:

• Observation of muscle weakness, tremor, and gait abnormalities

• Neurological examination showing areflexia and sensory loss

• Family history of neuropathic symptoms or similar gait disturbances

Electrophysiological Testing:

• Nerve conduction studies (NCS): Show slowed nerve conduction velocity consistent with demyelination

• Electromyography (EMG): Detects signs of chronic denervation and muscle atrophy

Genetic Testing:

• Confirms mutations in PMP22 or MPZ genes

• Helpful for distinguishing from other inherited neuropathies

• Allows for family counseling and carrier testing

Other Tests:

• MRI may be performed if central nervous system involvement is suspected

• Balance and coordination assessments (e.g., Romberg test)

Treatment

There is no cure for Roussy–Lévy syndrome. Treatment is symptomatic and supportive, aimed at preserving mobility, improving coordination, and managing complications. A multidisciplinary team including neurologists, physiotherapists, orthopedists, and occupational therapists is ideal.

1. Physical and Occupational Therapy:

• Strengthening and stretching exercises to maintain muscle function and joint mobility

• Balance training to reduce fall risk

• Occupational therapy to improve daily living activities and hand function

2. Orthopedic Management:

• Custom orthotic devices for foot drop or pes cavus (e.g., ankle-foot orthoses)

• Corrective surgery for severe foot deformities or scoliosis (in selected cases)

3. Medications:

• Anticonvulsants (e.g., gabapentin or pregabalin) for neuropathic pain, if present

• Beta-blockers or primidone may be tried for disabling tremor, although often with limited effect

4. Supportive Devices:

• Walking aids such as canes or walkers for severe ataxia

• Adaptive tools for handwriting or gripping objects

Prognosis

Roussy–Lévy syndrome is a slowly progressive but non-life-threatening disorder. With early diagnosis and supportive care, many individuals are able to maintain independence and participate in daily activities. However, some patients may eventually require mobility assistance due to worsening balance and muscle weakness.

Intellectual abilities are typically normal, and lifespan is not affected. Quality of life can be greatly improved through physical therapy, assistive devices, and regular monitoring by a neuromuscular specialist. Genetic counseling is recommended for affected families to understand inheritance risks and plan for future generations.