Muscle atrophy, back pain, and nerve root hypertrophy turned out to be this kind of disease!

Peroneal muscular atrophy ( Charcot-Marie-tooth disease , CMT ), also known as hereditary motor and sensory neuropathy ( HMSN ), is a group of peripheral nerve single-gene genetic diseases with high clinical and genetic heterogeneity
.

The main clinical manifestations are progressive symmetrical distal limb muscle weakness and muscle atrophy, sensory disturbances and tendon reflexes decreased or disappeared

Peroneal muscular atrophy ( Charcot-Marie-tooth disease , CMT ), also known as hereditary motor and sensory neuropathy ( HMSN ), is a group of peripheral nerve single-gene genetic diseases with high clinical and genetic heterogeneity

Imaging features

MRI is a valuable aid to support the clinical diagnosis of CMT .
Nerve roots are usually enlarged and thickened with onion bulb sign ( see the above case for details ) , which indicates hypertrophic demyelination .

MRI is a valuable aid to support the clinical diagnosis of CMT .

Nerve roots are usually enlarged and thickened with the diagnosis of onion ball sign ( see the above case for details ) , which indicates hypertrophic demyelination .

Who has CMT ?

Who has CMT ? Who has CMT ?

As a group of clinical and genetic heterogeneous neuropathy, CMT occurs all over the world, with an overall incidence of about 1/2500 , but the same pathogenic mutation has different carrying rates in different populations and ethnicities
.

Compared with Asian CMT , the mutation in GJB1 has a higher carrying rate in European CMT patients

As a group of clinical and genetic heterogeneous neuropathy, CMT occurs all over the world, with an overall incidence of about 1/2500 , but the same pathogenic mutation has different carrying rates in different populations and ethnicities

What symptoms can CMT cause? What symptoms can CMT cause?

CMT is mostly onset in children and adolescents.

The typical clinical feature is the earliest involvement of both lower limbs, manifested as progressive symmetrical weakness of the distal muscles, muscle atrophy or hypertrophy, weakened or disappeared tendon reflexes, and accompanied by skeletal deformities, including crane legs -Like deformities, arched feet and hammer toes

CMT is mostly onset in children and adolescents.
The typical clinical feature is the earliest involvement of both lower limbs, manifested as progressive symmetrical weakness of the distal muscles, muscle atrophy or hypertrophy, weakened or disappeared tendon reflexes, and accompanied by skeletal deformities, including crane legs -Like deformities, arched feet and hammer toes

Most CMT patients have a certain degree of physical disability, but they rarely affect the muscles involved in important functions such as breathing, so they are not life-threatening.

What are the types of CMT ? What are the types of CMT ?

There are many different types of
CMT , and some of the clinical symptoms will vary depending on the genetic pattern, age of onset, and whether axons or myelin are involved .

It is precisely because of its clinical heterogeneity that there is no expert consensus on the classification of CMT .

There are many different types of

According to the age of onset: early infancy ( <2 years old), children ( 2 to 10 years old), adolescents ( 10 to 20 years old), adults ( 20 to 50 years old) and late adulthood ( >50 years old)

According to electrophysiological results: CMT is divided into demyelination and axonal neuropathy

According to the mode of inheritance: CMT has an autosomal dominant, autosomal recessive or X- linked inheritance mode

Based on electrophysiological and pathological findings, as well as key clinical features, CMT was named hereditary motor and sensory neuropathy ( HMSN ) and classified as:

① HMSN I : Demyelinating subtype

① HMSN I : Demyelinating subtype

② HMSN II : Axon subtype

② HMSN II : Axon subtype

③ HMSN III : Dejerine Sottas disease

③ HMSN III : Dejerine Sottas disease

④ HMSN IV : Refsum disease

④ HMSN IV : Refsum disease

⑤ HMSN V : with pyramidal tract sign

⑤ HMSN V : with pyramidal tract sign

⑥ HMSN VI : with optic nerve atrophy

⑥ HMSN VI : with optic nerve atrophy

⑦ HMSN VII : with retinitis pigmentosa

⑦ HMSN VII : with retinitis pigmentosa

The latest classification integrates molecular genetic factors and is mainly divided into the following categories:

The latest classification integrates molecular genetic factors and is mainly divided into the following categories:

① CMT1 : Caused by abnormal myelin sheath
.

① CMT1 : Caused by abnormal myelin sheath
.

Among them, CMT1A is mainly caused by repeated mutations in the peripheral myelin protein 22 ( PMP22 ) gene
.
This protein is an important part of myelin sheath, and its overexpression can lead to abnormal structure and function of myelin sheath
.
On the contrary, insufficient expression of PMP22 protein can lead to recurrent demyelinating neuropathy, called hereditary pressure-susceptible peripheral neuropathy ( HNPP )
.

Among them, CMT1A is mainly caused by repeated mutations in the peripheral myelin protein 22 ( PMP22 ) gene
.
This protein is an important part of myelin sheath, and its overexpression can lead to abnormal structure and function of myelin sheath
.
On the contrary, insufficient expression of PMP22 protein can lead to recurrent demyelinating neuropathy, called hereditary pressure-susceptible peripheral neuropathy ( HNPP )
.

CMT1B by the encoding myelin protein zero ( MPZ , also referred to as P0 ) mutations cause, P0 protein is another key component of myelin
.
Most of the mutations in this gene are point mutations.
So far, more than 120 different point mutations
have been discovered .
The clinical symptoms of CMT1A and CMT1B are similar
.

CMT1B by the encoding myelin protein zero ( MPZ , also referred to as P0 ) mutations cause, P0 protein is another key component of myelin
.
Most of the mutations in this gene are point mutations.
So far, more than 120 different point mutations
have been discovered .
The clinical symptoms of CMT1A and CMT1B are similar
.

Other less common CMT1 are caused by mutations in the LITAF , EGR2 , PMP22, and NEFL genes
.

Other less common CMT1 are caused by mutations in the LITAF , EGR2 , PMP22, and NEFL genes
.

② CMT2 : It is caused by abnormal axons of peripheral nerve cells, which is less common than CMT1 .

② CMT2 : It is caused by abnormal axons of peripheral nerve cells, which is less common than CMT1 .

There are more than a dozen subtypes, and each subtype is related to mutations in specific genes
.
It usually occurs in childhood or adolescence
.
The clinical symptoms are similar to those in CMT1 , but the degree of disability and sensory loss in CMT2 patients is usually less than that in CMT1 patients
.
Certain types of CMT2 can cause speech or breathing problems due to involvement of the vocal cords or phrenic nerve
.

There are more than a dozen subtypes, and each subtype is related to mutations in specific genes
.
It usually occurs in childhood or adolescence
.
The clinical symptoms are similar to those in CMT1 , but the degree of disability and sensory loss in CMT2 patients is usually less than that in CMT1 patients
.
Certain types of CMT2 can cause speech or breathing problems due to involvement of the vocal cords or phrenic nerve
.

③ CMT3 or Dejerine-Sottas disease: is a particularly severe demyelinating neuropathies, onset in infancy
.

③ CMT3 or Dejerine-Sottas disease: is a particularly severe demyelinating neuropathies, onset in infancy
.

Clinically, there will be severe muscle atrophy, physical weakness, delayed motor skills development and sensory problems, and some will develop into severe disability, sensory loss and spinal curvature
.
Caused by mutations in multiple genes, including PMP22 , MPZ and EGR2 , there are both dominant and recessive inheritance modes
.

Clinically, there will be severe muscle atrophy, physical weakness, delayed motor skills development and sensory problems, and some will develop into severe disability, sensory loss and spinal curvature
.
Caused by mutations in multiple genes, including PMP22 , MPZ and EGR2 , there are both dominant and recessive inheritance modes
.

④ CMT4 : Including several different subtypes of demyelination, axon and motor neuropathy, it is an autosomal recessive genetic disease
.

④ CMT4 : Including several different subtypes of demyelination, axon and motor neuropathy, it is an autosomal recessive genetic disease
.

Each subtype is caused by mutations in different genes.
The special feature is that different mutations in this subtype may affect specific ethnic groups and produce different physiological or clinical characteristics
.
People with CMT4 usually have symptoms of leg weakness in childhood, and the inability to walk during adolescence develops
.

Each subtype is caused by mutations in different genes.
The special feature is that different mutations in this subtype may affect specific ethnic groups and produce different physiological or clinical characteristics
.
People with CMT4 usually have symptoms of leg weakness in childhood, and the inability to walk during adolescence develops
.

⑤ CMTX1 : It is the second most common type of CMT .

⑤ CMTX1 : It is the second most common type of CMT .

Such X -linked disease is GJB1 mutations caused, GJB1 encoding connexin 32
.
The protein is present in myelin sheath Schwann cells, which wraps nerve axons and forms myelin sheath
.
Men start to show moderate to severe disease symptoms in late childhood or adolescence; women usually have milder or asymptomatic symptoms than men
.

Such X -linked disease is GJB1 mutations caused, GJB1 encoding connexin 32
.
The protein is present in myelin sheath Schwann cells, which wraps nerve axons and forms myelin sheath
.
Men start to show moderate to severe disease symptoms in late childhood or adolescence; women usually have milder or asymptomatic symptoms than men
.

What causes peroneal muscle atrophy?

What causes peroneal muscle atrophy? What causes peroneal muscle atrophy?

Nerve cells send electrical signals to the elongated axons in the cells to transmit information to distant targets
.
Myelin sheath is the surrounding layer outside the axon.
Its function is similar to the insulating layer on the wire, which helps the high-speed transmission of electrical signals
.
If the axons and myelin sheaths are damaged, the signals along the nerves and axons are either slow or weak.
As a result, peripheral nerve cells cannot activate muscles or transmit sensory information from the limbs back to the spinal cord and brain
.

Nerve cells send electrical signals to the elongated axons in the cells to transmit information to distant targets
.
Myelin sheath is the surrounding layer outside the axon.
Its function is similar to the insulating layer on the wire, which helps the high-speed transmission of electrical signals
.
If the axons and myelin sheaths are damaged, the signals along the nerves and axons are either slow or weak.
As a result, peripheral nerve cells cannot activate muscles or transmit sensory information from the limbs back to the spinal cord and brain
.

Proteins that may be involved in the intracellular pathway of CMT

Proteins that may be involved in the intracellular pathway of CMT

 CMT is a genetic disease, and its pathogenic genes encode proteins related to the structure and function of peripheral nerve axons or myelin sheath
.
In the CMT has been determined 80 multiple genes, each gene is associated with one or more diseases, multiple genes may be one type of CMT associated
.

 CMT is a genetic disease, and its pathogenic genes encode proteins related to the structure and function of peripheral nerve axons or myelin sheath
.
In the CMT has been determined 80 multiple genes, each gene is associated with one or more diseases, multiple genes may be one type of CMT associated
.

The most common clinically CMT1A subtype caused by PMP22 gene duplication , which accounts for about 40% to 50% , is located at 17p12 and is prone to genome rearrangement .
GJB1 point mutation caused CMTX type accounts for about 10% , MZP mutations caused CMT1B type accounted for 2.
5% to 5% .

The most common clinically CMT1A subtype caused by PMP22 gene duplication , which accounts for about 40% to 50% , is located at 17p12 and is prone to genome rearrangement .
GJB1 point mutation caused CMTX type accounts for about 10% , MZP mutations caused CMT1B type accounted for 2.
5% to 5% .

How to diagnose CMT ?

How to diagnose CMT ? How to diagnose CMT ?

In clinical diagnosis and treatment , for patients with atypical clinical manifestations and no positive family history, neuroelectrophysiological examination should be performed as soon as possible to achieve early diagnosis and early treatment
.
Electroneurophysiological examination is a good guide for diagnosis, disease curative effect and prognostic judgment
.
Genetic diagnosis is a reliable and accurate diagnosis method for this gene.
In developed countries, genetic diagnosis is gradually becoming the main basis for diagnosing CMT .
If conditions permit, genetic testing should be performed as soon as possible, especially for patients with family history.
Detection is particularly important, but there are still some patients whose pathogenic genes are currently unclear
.

In clinical diagnosis and treatment , for patients with atypical clinical manifestations and no positive family history, neuroelectrophysiological examination should be performed as soon as possible to achieve early diagnosis and early treatment
.
Electroneurophysiological examination is a good guide for diagnosis, disease curative effect and prognostic judgment
.
Genetic diagnosis is a reliable and accurate diagnostic method for the gene.
In developed countries, genetic diagnosis is gradually becoming the main basis for diagnosis and treatment of CMT .
If conditions permit, genetic testing should be performed as soon as possible, especially for patients with family history.
Genetic testing is particularly important, but there are still some patients whose disease-causing genes are currently unclear
.

Kang Xu’s peroneal muscular atrophy products perform second-generation sequencing on the exon regions of peripheral neuropathy-related genes to assist in the differential diagnosis of such diseases; it also includes copy number variation detection of common disease-causing genes as the second-generation Supplement to sequencing products; In addition, prenatal screening of related products is provided
.

Kang Xu’s peroneal muscular atrophy products perform second-generation sequencing on the exon regions of peripheral neuropathy-related genes to assist in the differential diagnosis of such diseases; it also includes copy number variation detection of common disease-causing genes as the second-generation Supplement to sequencing products; In addition, prenatal screening of related products is provided
.
Screening

product code	product name	Test content
LM-NE0801	Peripheral neuropathy and spastic paraplegia test kit	Second-generation sequencing of related gene exons + MLPA detection of PMP22 gene
LP-NE1202	Detection of Large Fragment Variation in Peroneal Muscular Atrophy -1	IGHMBP2 gene MLPA detection
LP-NE1204	Detection of Large Fragment Variation in Peroneal Muscular Atrophy -2	GDAP1 , MTMR2 , SBF2 , SH2TC2 , EGR2 , PRX gene MLPA detection
LP-NE1206	Detection of Large Fragment Variation in Peroneal Muscular Atrophy -3	PMP22 gene MLPA test

product code

product name

Test content

LM-NE0801

Peripheral neuropathy and spastic paraplegia test kit

Second-generation sequencing of related gene exons + MLPA detection of PMP22 gene

LP-NE1202

Detection of Large Fragment Variation in Peroneal Muscular Atrophy -1

IGHMBP2 gene MLPA detection

LP-NE1204

Detection of Large Fragment Variation in Peroneal Muscular Atrophy -2

GDAP1 , MTMR2 , SBF2 , SH2TC2 , EGR2 , PRX gene MLPA detection

LP-NE1206

Detection of Large Fragment Variation in Peroneal Muscular Atrophy -3

PMP22 gene MLPA test

product code

product name

Test content

product code

product code

product code

product name

product name

product name

Test content

Test content

Test content

LM-NE0801

Peripheral neuropathy and spastic paraplegia test kit

Second-generation sequencing of related gene exons + MLPA detection of PMP22 gene

LM-NE0801

LM-NE0801

LM-NE0801

Peripheral neuropathy and spastic paraplegia test kit

Peripheral neuropathy and spastic paraplegia test kit

Peripheral neuropathy and spastic paraplegia test kit

Second-generation sequencing of related gene exons + MLPA detection of PMP22 gene

Second-generation sequencing of related gene exons + MLPA detection of PMP22 gene

Second-generation sequencing of related gene exons + MLPA detection of PMP22 gene

LP-NE1202

Detection of Large Fragment Variation in Peroneal Muscular Atrophy -1

IGHMBP2 gene MLPA detection

LP-NE1202

LP-NE1202

LP-NE1202

Detection of Large Fragment Variation in Peroneal Muscular Atrophy -1

Detection of Large Fragment Variation in Peroneal Muscular Atrophy -1

Detection of Large Fragment Variation in Peroneal Muscular Atrophy -1

IGHMBP2 gene MLPA detection

IGHMBP2 gene MLPA detection

IGHMBP2 gene MLPA detection

LP-NE1204

Detection of Large Fragment Variation in Peroneal Muscular Atrophy -2

GDAP1 , MTMR2 , SBF2 , SH2TC2 , EGR2 , PRX gene MLPA detection

LP-NE1204

LP-NE1204

LP-NE1204

Detection of Large Fragment Variation in Peroneal Muscular Atrophy -2

Detection of Large Fragment Variation in Peroneal Muscular Atrophy -2

Detection of Large Fragment Variation in Peroneal Muscular Atrophy -2

GDAP1 , MTMR2 , SBF2 , SH2TC2 , EGR2 , PRX gene MLPA detection

GDAP1 , MTMR2 , SBF2 , SH2TC2 , EGR2 , PRX gene MLPA detection

GDAP1 , MTMR2 , SBF2 , SH2TC2 , EGR2 , PRX gene MLPA detection

LP-NE1206

Detection of Large Fragment Variation in Peroneal Muscular Atrophy -3

PMP22 gene MLPA test

LP-NE1206

LP-NE1206

LP-NE1206

Detection of Large Fragment Variation in Peroneal Muscular Atrophy -3

Detection of Large Fragment Variation in Peroneal Muscular Atrophy -3

Detection of Large Fragment Variation in Peroneal Muscular Atrophy -3

PMP22 gene MLPA test

PMP22 gene MLPA test

PMP22 gene MLPA test

 

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