Dejerine–Sottas disease, also known as, Dejerine–Sottas neuropathy, progressive hypertrophic interstitial polyneuropathy of childhood and onion bulb neuropathy (and, ''hereditary motor and sensory polyneuropathy type III'' and ''

Charcot–Marie–Tooth disease Charcot–Marie–Tooth disease (CMT) is a hereditary motor and sensory neuropathy of the peripheral nervous system characterized by progressive loss of muscle tissue and touch sensation across various parts of the body. This disease is the mos ...

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 characterised by damage to the

peripheral nerve A nerve is an enclosed, cable-like bundle of nerve fibers (called axons) in the peripheral nervous system. A nerve transmits electrical impulses. It is the basic unit of the peripheral nervous system. A nerve provides a common pathway for the e ...

s and resulting progressive muscle wasting. 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, mi ...

s in a various

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

s and currently has no known cure. The disorder is named for

Joseph Jules Dejerine Joseph Jules Dejerine (3 August 1849 – 26 February 1917), was a French neurologist. Biography Joseph Jules Dejerine was born to French parents in Geneva, Switzerland, where his father was a carriage proprietor. During the Franco-Prussian War ...

and

Jules Sottas Jules Sottas (22 May 1866, Paris – 28 September 1945, Paris) was a French neurologist.IDREF.fr
(bibliography) He studie ...

, French neurologists 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 usually more severe and rapidly progressive than in the other more common

s. Some patients may never walk and solely use wheelchairs by the end of their first decade, while others may need only a cane (walking stick) or similar support through life. Dejerine–Sottas disease is characterized by moderate to severe lower and upper extremity weakness and loss of sensation, which occur mainly in the lower legs, forearms, feet and hands. Loss of muscle mass and reduced muscle tone can occur as the disease progresses. Other symptoms may include pain in the extremities, curvature of the spine, clawed hands, foot deformities,

ataxia Ataxia is a neurological sign consisting of lack of voluntary coordination of muscle movements that can include gait abnormality, speech changes, and abnormalities in eye movements. Ataxia is a clinical manifestation indicating dysfunction of ...

, peripheral

areflexia Hyporeflexia is the reduction or absence of normal bodily reflexes (areflexia). 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 neu ...

, and slow acquisition of motor skills 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. Infants can be born with it but more commonly acquire it in infancy or later in life. In many cases it may result in reduced or limited vision. Due to the invol ...

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 condit ...

, or mild hearing loss.

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 American and British English spelling differences#-re, -er, spelling differences), is a long, slender projection of a nerve cell, or neuron, in vertebrates, th ...

or the proteins found in

myelin Myelin is a lipid-rich material that surrounds nerve cell axons (the nervous system's "wires") to insulate them and increase the rate at which electrical impulses (called action potentials) are passed along the axon. The myelinated axon can be ...

. Specifically, it has been associated with

s in '' MPZ'', ''

PMP22 Growth arrest-specific protein 3 (GAS-3), also called peripheral myelin protein 22 (PMP22), is a protein which in humans is encoded by the ''PMP22'' gene. PMP22 is a 22 kDa transmembrane glycoprotein made up of 160 amino acids, and is mainly exp ...

'', '' 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 (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation ...

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 effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...

autosomal recessive In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...

manner.

Diagnosis

On medical imaging, the nerves of the extremities (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 ...

in some cases) appear enlarged due to

hypertrophy Hypertrophy is the increase in the volume of an organ or tissue due to the enlargement of its component cells. It is distinguished from hyperplasia, in which the cells remain approximately the same size but increase in number.Updated by Linda J ...

of the connective

interstitial tissue An interstitial space or interstice is a space between structures or objects. In particular, interstitial may refer to: Biology * Interstitial cell tumor * Interstitial cell, any cell that lies between other cells * Interstitial collagenase, ...

, giving the nerves a distinct "onion-bulb" appearance. Peripheral (and possibly cranial) nerve excitability and conduction speed are reduced.

Treatment

Management is symptomatic for this condition .

References

External links