Dejerine–Sottas disease, also known as, Dejerine–Sottas syndrome, hereditary motor and sensory polyneuropathy type III, and Charcot–Marie–Tooth disease type 3, is a

hereditary Heredity, also called inheritance or biological inheritance, is the passing on of traits from parents to their offspring; either through asexual reproduction or sexual reproduction, the offspring cells or organisms acquire the genetic inform ...

neurological disorder Neurological disorders represent a complex array of medical conditions that fundamentally disrupt the functioning of the nervous system. These disorders affect the brain, spinal cord, and nerve networks, presenting unique diagnosis, treatment, and ...

characterized by damage to the

peripheral 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 electrochemical nerve impulses called ...

s, demyelination, and resulting progressive muscle wasting and

somatosensory The somatosensory system, or somatic sensory system is a subset of the sensory nervous system. The main functions of the somatosensory system are the perception of external stimuli, the perception of internal stimuli, and the regulation of bod ...

loss. The condition is caused by

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, ...

s in various

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

s and currently has no known cure. The disorder is named for Joseph Jules Dejerine and Jules Sottas, French

neurologists Neurology (from , "string, nerve" and the suffix -logia, "study of") is the branch of medicine dealing with the diagnosis and treatment of all categories of conditions and disease involving the nervous system, which comprises the brain, the s ...

who first described it.

Signs and symptoms

Onset occurs in infancy or early childhood, usually before three years of age. Progression is slow until the teenage years at which point it may accelerate, resulting in severe disability. Symptoms are more severe and rapidly progressive than in the other more common Charcot–Marie–Tooth diseases. Some patients may never walk and will be reliant on wheelchair use by the end of their first decade, while others may need only a cane, crutches, or similar support through most of their lives, but this is rare. Dejerine–Sottas disease is characterized by moderate to severe lower and upper extremity

weakness Weakness is a symptom of many different medical conditions. The causes are many and can be divided into conditions that have true or perceived muscle weakness. True muscle weakness is a primary symptom of a variety of skeletal muscle diseases, ...

and loss of sensation, mainly in the lower legs, forearms, feet, and hands. Loss of

muscle mass Skeletal muscle (commonly referred to as muscle) is one of the three types of vertebrate muscle tissue, the others being cardiac muscle and smooth muscle. They are part of the voluntary muscular system and typically are attached by tendons to bo ...

and reduced

muscle tone In physiology, medicine, and anatomy, muscle tone (residual muscle tension or tonus) is the continuous and passive partial contraction of the muscles, or the muscle's resistance to passive stretch during resting state.O’Sullivan, S. B. (2007) ...

usually occur as the disease progresses. Other symptoms may include pain in the extremities, curvature of the spine, clawed hands, foot deformities,

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 ...

, peripheral areflexia, and slow acquisition of

motor skills A motor skill is a function that involves specific movements of the body's muscles to perform a certain task. These tasks could include walking, running, or riding a bike. In order to perform this skill, the body's nervous system, muscles, and b ...

in childhood. Symptoms that are less common can include limitation of eye movements, other eye problems such as

nystagmus Nystagmus is a condition of involuntary (or voluntary, in some cases) Eye movement (sensory), eye movement. People can be born with it but more commonly acquire it in infancy or later in life. In many cases it may result in visual impairment, re ...

anisocoria Anisocoria is a condition characterized by an unequal size of the eyes' pupils. Affecting up to 20% of the population, anisocoria is often entirely harmless, but can be a sign of more serious medical problems. Causes Anisocoria is a common cond ...

, or moderate to severe

hearing loss Hearing loss is a partial or total inability to hear. Hearing loss may be present at birth or acquired at any time afterwards. Hearing loss may occur in one or both ears. In children, hearing problems can affect the ability to acquire spo ...

Causes

Dejerine–Sottas neuropathy is caused by a genetic defect either in the proteins found in

axons An axon (from Greek ἄξων ''áxōn'', axis) or nerve fiber (or nerve fibre: see spelling differences) is a long, slender projection of a nerve cell, or neuron, in vertebrates, that typically conducts electrical impulses known as action pot ...

or the proteins found in

myelin 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 ...

. Specifically, it has been associated with

s in '' MPZ'', ''

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 ...

'', '' PRX'', and ''

EGR2 Early growth response protein 2 is a protein that in humans is encoded by the ''EGR2'' gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA t ...

s. The disorder is inherited in an

autosomal dominant In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the Phenotype, effect of a different variant of the same gene on Homologous chromosome, the other copy of the chromosome. The firs ...

autosomal recessive In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the Phenotype, effect of a different variant of the same gene on Homologous chromosome, the other copy of the chromosome. The firs ...

manner.

Diagnosis

On medical imaging, the peripheral and

cranial nerves Cranial nerves are the nerves that emerge directly from the brain (including the brainstem), of which there are conventionally considered twelve pairs. Cranial nerves relay information between the brain and parts of the body, primarily to and f ...

are enlarged by redundant

connective tissue Connective tissue is one of the four primary types of animal tissue, a group of cells that are similar in structure, along with epithelial tissue, muscle tissue, and nervous tissue. It develops mostly from the mesenchyme, derived from the mesod ...

. On

histology Histology, also known as microscopic anatomy or microanatomy, is the branch of biology that studies the microscopic anatomy of biological tissue (biology), tissues. Histology is the microscopic counterpart to gross anatomy, which looks at large ...

, this enlargement gives the nerves the appearance of an onion-bulb. Nerve excitability and conduction speed are reduced.

Treatment

Management is symptomatic for this condition.

References

External links