Roussy-Levy Syndrome - Causes, Symptoms, and Diagnosis

Introduction

Roussy-Levy syndrome is a neuromuscular disorder that was first described by Roussy and Levy in the year 1926. It is a rare genetic condition with an autosomal dominant inheritance pattern. In the year 1886, Charcot and Marie described the condition called Charcot-Marie tooth syndrome which had similar clinical features to the Roussy-Levy syndrome. Hence Roussy-Levy syndrome was described as a hypertrophic variant of Charcot-Marie disease type 1. This article will discuss Roussy-Levy syndrome and its clinical features in detail.

What Is Roussy-Levy Syndrome?

Roussy-Levy syndrome is a rare genetic condition that occurs due to genetic alterations in the PMP22 (peripheral myelin protein 22) gene and MPZ (myelin protein zero) gene. This condition is characterized by muscle weakness and atrophy, sensory ataxia, absence of neurologic reflexes in the hands and lower legs, and elevation in the plantar arch of the foot. All these clinical features are similar to the condition of Charcot-Marie syndrome. And the added specifics to the Roussy-Levy syndrome are an unsteady gait and rhythmic shaking of the hands.

What Are the PMP22 Gene and MPZ Gene?

• The PMP22 (peripheral myelin protein 22) gene in humans is responsible for providing instructions for the production of a protein called the peripheral myelin protein 22 (PMP22).

• PMP22 is located in the peripheral nervous system which is a part of the nervous system located outside of the brain and the spinal cord and plays an important role in receiving and sending signals from the brain and spinal cord to other parts of the body.

• They are also located in the insulating layer (myelin sheath) that surrounds the nervous system of the brain and spinal cord.

• This gene is located on chromosome 17.

• In most cases of Roussy-Levy syndrome, the patients have genetic mutations in the PMP22 gene. The disease occurs when there is an extra copy of the mutated gene resulting from a small genetic duplication on chromosome 17.

• The MPZ gene is responsible for providing instructions for the production of a protein called Myelin Protein Zero (MPZ).

• This gene is found in chromosome 1.

• MPZ protein is found excessively in the myelin sheath that surrounds the nervous system and promotes the transmission of nerve impulses.

• Genetic changes in the Myelin Protein Zero gene results in Roussy-Levy syndrome.

How Is Roussy-Levy Syndrome Inherited?

A genetic disease is caused when there are alterations or mutations in the individual's primary genetic material. These diseases are either inherited from an affected parent with a pathologic gene variant or by random genetic mutations due to any underlying reasons. Roussy-Levy syndrome is inherited in an autosomal dominant pattern. In this type of inheritance pattern, a single copy of the altered gene in a cell is sufficient to cause the genetic disease. In most cases, the one affected parent carries the pathologic variant gene. The probability of passing down an abnormal gene from the affected parents is 50 percent in each pregnancy.

What Are the Signs and Symptoms?

The signs and symptoms of Roussy-Levy syndrome start to occur at the age of one to 23 months or between the ages of two to eleven years. This condition has a diverse clinical presentation.

• Acute Demyelinating Polyneuropathy: This condition causes myelin breakdown and axonal degeneration which affects the normal transmission of electric nerve impulses from the brain and spinal cord to other parts of the body and prevents the muscle from responding effectively. That results in progressive muscle weakness and loss of sensory function.

• Areflexia: This condition results in absence of muscle reflexes to a stimulus.

• Unsteady Gait: This condition results in an abnormality in walking that increases the risk of falls.

• Talipes Equinovarus: This condition is often referred to as the club foot that causes an abnormal twist of the foot in the affected individual.

• Sensory Impairment: Impairment in the primary senses that is mediated by the peripheral nervous system such as touch, pain, and temperature.

• Skeletal Muscle Atrophy: this condition causes decreased muscle mass.

• Scoliosis: Presence of abnormal sideways curvature of the backbone.

• Babinski Sign: Damage to the corticospinal tract results in a positive Babinski sign. Stimulation along the bottom of the foot causes extension of the big toe.

• Distal Amyotrophy: weakness of muscles along the distal portion of the extremities.

• Frequent falls.

• Gait Ataxia: Condition causing poor muscle control resulting in a clumsy walking pattern.

• Genu Valgum: Lower leg abnormality often called knock knees where the knees are turned inward.

• Impaired pain sensation.

• Muscle weakness in lower extremities.

• Nystagmus: Rhythmic uncontrolled rapid and repetitive movements of the eyes.

• Postural Tremor: Condition causing tremors with the limbs in a fixed position.

• High-arched foot.

How Is Roussy-Levy Syndrome Diagnosed?

The diagnosis of Roussy-Levy syndrome is made through a detailed history taking and by thorough physical examination of the patient to assess the symptoms. The diagnosis of the condition is based on the symptoms of the patient.

• The clinician may perform nerve conduction studies to assess the speed of the electric signals passing through the nerves.

• A diagnostic procedure called electromyography may be performed to assess the functions of the muscles and the nerves supplying them.

• The doctor may perform a nerve biopsy for the assessment of the nerves in the laboratory to rule out other nerve disorders.

• The doctor may refer the affected patient and the family for genetic testing to detect the genetic defects causing the condition.

• Radiological investigations are also performed to assess skeletal deformities.

How Is It Treated?

Roussy-Levy syndrome is a genetic condition and currently, there are no treatment options to cure the disease, however, the signs and symptoms of the affected patient can be treated.

• The doctor may refer the patient to a physical therapist to maintain the patient’s range of motion, muscle strength, endurance, and flexibility. Especially water therapy has been shown to be effective in improving the symptoms.

• They are referred to an orthopedic surgeon for the surgical correction of limb deformities. Post-surgical rehabilitation and the use of splinting and braces help in improving function and decreasing discomfort.

Conclusion

Roussy-Levy syndrome is an extremely rare genetic condition present from birth. This condition is of an autosomal dominant inheritance pattern. This condition is characterized by neuromuscular disorders and it has diverse clinical manifestations. Most cases affected with Roussy-Levy syndrome have genetic alterations in the PMP22 gene and MPZ gene which are responsible for the proteins located in the myelin sheath of a nervous system. As of now, there is no cure for this condition however prognosis for treating the patient's signs and symptoms is good.