Roussy–Lévy syndrome, also known as Roussy–Lévy areflexic dystasia, is a rare

disorder Disorder may refer to randomness, a lack of intelligible pattern, or: Healthcare * Disorder (medicine), a functional abnormality or disturbance * Mental disorder or psychological disorder, a psychological pattern associated with distress or disab ...

of humans that results in progressive

muscle wasting Muscle atrophy is the loss of skeletal muscle mass. It can be caused by immobility, aging, malnutrition, medications, or a wide range of injuries or diseases that impact the musculoskeletal or nervous system. Muscle atrophy leads to muscle weakne ...

. It is caused by a

mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, ...

of the genes that code for

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

s necessary for the functioning of the

myelin sheath Myelin Sheath ( ) is a lipid-rich material that in most vertebrates surrounds the axons of neurons to insulate them and increase the rate at which electrical impulses (called action potentials) pass along the axon. The myelinated axon can be lik ...

affecting the conductance of

nerve A nerve is an enclosed, cable-like bundle of nerve fibers (called axons). Nerves have historically been considered the basic units of the peripheral nervous system. A nerve provides a common pathway for the Electrochemistry, electrochemical nerv ...

signals and resulting in loss of muscles' ability to move. The condition affects people from infants through adults.

Signs and symptoms

Symptoms of the Roussy–Lévy syndrome mainly stem from damage and the resulting progressive

muscle atrophy Muscle atrophy is the loss of skeletal muscle mass. It can be caused by immobility, aging, malnutrition, medications, or a wide range of injuries or diseases that impact the musculoskeletal or nervous system. Muscle atrophy leads to muscle weakne ...

. Neurological damage may result in absent tendon

reflex In biology, a reflex, or reflex action, is an involuntary, unplanned sequence or action and nearly instantaneous response to a stimulus. Reflexes are found with varying levels of complexity in organisms with a nervous system. A reflex occurs ...

es (

areflexia Hyporeflexia is the reduction or absence of normal bodily reflexes. It can be detected through the use of a reflex hammer and is the opposite of hyperreflexia. Hyporeflexia is generally associated with a deficit in the lower motor neurons (at t ...

), some distal sensory loss and decreased excitability of muscles to galvanic and faradic stimulation. Progressive muscle wasting results in weakness of

distal Standard anatomical terms of location are used to describe unambiguously the anatomy of humans and other animals. The terms, typically derived from Latin or Greek roots, describe something in its standard anatomical position. This position provi ...

limb muscles (especially the peronei), gait

ataxia Ataxia (from Greek α- negative prefix+ -τάξις rder= "lack of order") is a neurological sign consisting of lack of voluntary coordination of muscle movements that can include gait abnormality, speech changes, and abnormalities in e ...

, pes cavus, postural tremors and static tremor of the upper limbs and foot deformity. These symptoms frequently translate into delayed onset of ability to walk, loss of coordination and balance,

foot drop Foot drop is a gait abnormality in which the dropping of the forefoot happens out of weakness, irritation or damage to the deep fibular nerve (deep peroneal), including the sciatic nerve, or paralysis of the muscles in the anterior portion of th ...

, and foot-bone deformities. They are usually first observed during infancy or early childhood, and slowly progress until about age 30, at point progression may stop in individuals.

Causes

The Roussy–Lévy syndrome has been associated with two

s: a

duplication Duplication, duplicate, and duplicator may refer to: Biology and genetics * Gene duplication, a process which can result in free mutation * Chromosomal duplication, which can cause Bloom and Rett syndrome * Polyploidy, a phenomenon also known ...

of the ''

PMP22 Peripheral myelin protein 22 (PMP22), also called Growth arrest-specific protein 3 (GAS-3), is a protein which in humans is encoded by the ''PMP22'' gene. Mutations in ''PMP22'' cause changes in the expression of peripheral myelin protein 22 whic ...

'' gene that carries the instructions for producing the

peripheral myelin protein 22 Peripheral myelin protein 22 (PMP22), also called Growth arrest-specific protein 3 (GAS-3), is a protein which in humans is encoded by the ''PMP22'' gene. Mutations in ''PMP22'' cause changes in the expression of peripheral myelin protein 22 whic ...

, a critical component of the

; and a

missense mutation In genetics, a missense mutation is a point mutation in which a single nucleotide change results in a codon that codes for a different amino acid. It is a type of nonsynonymous substitution. Missense mutations change amino acids, which in turn alt ...

in the ''MPZ'' gene which codes for

myelin protein zero Myelin protein zero (MPZ), also Myelin protein P0, is a single membrane glycoprotein which in humans is encoded by the ''MPZ'' gene. P0 is a major structural component of the myelin sheath in the peripheral nervous system (PNS). Myelin protein ...

, a major structural protein of peripheral myelin. As ''PMP22'' mutations are also associated with

Charcot–Marie–Tooth disease Charcot-Marie-Tooth disease (CMT) is an inherited neurological disorder that affects the peripheral nerves responsible for transmitting signals between the brain, spinal cord, and the rest of the body. This is the most common inherited neuropath ...

type 1A and ''MPZ'' mutations are associated with Charcot–Marie–Tooth disease type 1B, it remains the subject of discussion whether the Roussy–Lévy syndrome is a separate entity or a specific phenotype of either disorder. It can also be caused by childhood trauma.

Pathophysiology

In common with other types of

, examination reveals decreased

nerve conduction velocity In neuroscience, nerve conduction velocity (CV) is the speed at which an electrochemical impulse propagates down a neural pathway. Conduction velocities are affected by a wide array of factors, which include age, sex, and various medical conditio ...

and histologic features of a hypertrophic demyelinating neuropathy.

Electromyography Electromyography (EMG) is a technique for evaluating and recording the electrical activity produced by skeletal muscles. EMG is performed using an instrument called an electromyograph to produce a record called an electromyogram. An electromyo ...

shows signs of mild neurogenic damage while

biopsy A biopsy is a medical test commonly performed by a surgeon, interventional radiologist, an interventional radiologist, or an interventional cardiology, interventional cardiologist. The process involves the extraction of sampling (medicine), sample ...

shows onion bulb formations; the appearance of these formations is what primarily led

Gustave Roussy Gustave Roussy (; 24 November 1874 – 30 September 1948) was a Swiss-French neuropathologist born in Vevey, Switzerland. Career As a hospital interne in Paris, Roussy worked under neurologists Pierre Marie and Joseph Jules Dejerine. In 1907 ...

and Gabrielle Lévy, the scientists who first described the disorder, to classify it as a variant of

. To create a working nerve, neurons,

Schwann cells Schwann cells or neurolemmocytes (named after German physiologist Theodor Schwann) are the principal glia of the peripheral nervous system (PNS). Glial cells function to support neurons and in the PNS, also include Satellite glial cell, satellite ...

, and

fibroblasts A fibroblast is a type of biological cell typically with a spindle shape that synthesizes the extracellular matrix and collagen, produces the structural framework ( stroma) for animal tissues, and plays a critical role in wound healing. Fibrobla ...

must work together. Molecular signals are exchanged between

and

neurons A neuron (American English), neurone (British English), or nerve cell, is an membrane potential#Cell excitability, excitable cell (biology), cell that fires electric signals called action potentials across a neural network (biology), neural net ...

to regulate survival and differentiation of a nerve. However, these signals are disrupted in patients with the Roussy–Lévy syndrome.

Diagnosis

While the clinical picture may point towards the diagnosis of the Roussy–Lévy syndrome, the condition can only be confirmed with absolute certainty by carrying out

KT or MRT KT, kT or kt may refer to: Arts and media * KT Bush Band, group formed by musician Kate Bush * ''KT'' (film), a 2002 Japanese political thriller film, based on the real-life kidnapping of Kim Dae-jung * '' Karlstads-Tidningen'' (''KT''), a Swed ...

Treatment

For Roussy–Lévy syndrome no pharmacological treatment required. Treatment options focus on corrective therapy. Patients tend to benefit greatly from

physical therapy Physical therapy (PT), also known as physiotherapy, is a healthcare profession, as well as the care provided by physical therapists who promote, maintain, or restore health through patient education, physical intervention, disease preventio ...

(especially water therapy as it does not place excessive pressure on the muscles), while moderate activity is often recommended to maintain movement, flexibility, muscle strength and endurance. While no medicines are reported to treat the disorder, patients are advised to avoid certain medications as they may aggravate the symptoms. Patients with foot deformities may benefit from

corrective surgery Surgery is a medical specialty that uses manual and instrumental techniques to diagnose or treat pathological conditions (e.g., trauma, disease, injury, malignancy), to alter bodily functions (e.g., malabsorption created by bariatric surgery s ...

, which, however, is usually a last resort. Most such surgeries include straightening and pinning the toes, lowering the arch, and sometimes, fusing the ankle joint to provide stability. Recovering from these surgeries is oftentimes long and difficult. Proper foot care including custom-made shoes and leg braces may minimize discomfort and increase function.

Prognosis

The Roussy–Lévy syndrome is not a fatal disease and

life expectancy Human life expectancy is a statistical measure of the estimate of the average remaining years of life at a given age. The most commonly used measure is ''life expectancy at birth'' (LEB, or in demographic notation ''e''0, where '' ...

is normal.

History

References

External links

{{DEFAULTSORT:Roussy-Levy syndrome Autosomal dominant disorders Neurogenetic disorders Syndromes