What are the other Names for this Condition? (Also known as/Synonyms)

• Charcot-Marie-Tooth Disease (CMT), Subtype 4E
• Congenital Hypomyelination Neuropathy
• Hypomyelination Neuropathy

What is Congenital Hypomyelinating Neuropathy? (Definition/Background Information)

• Congenital Hypomyelinating Neuropathy (CHN) is a very rare, progressive, irreversible, and congenital (genetic) disorder that affects the nervous system
• Nerves from the brain and spinal cord that supply the muscles and organs are damaged at birth in those with CHN, causing neuropathy (nerve condition involving weakness and numbness)
• Individuals with this disorder produce little or no myelin, which is the biological insulator that enables nerves to send signals throughout the body
• Individuals with Congenital Hypomyelinating Neuropathy exhibit low muscle tone (hypotonia), muscle weakness associated with poor balance and coordination (ataxia), impaired movements and sensations in the arms and legs (neuropathy), and an absence of reflexes (areflexia)
• This genetic disorder is caused by mutations in two specific genes (MPZ and EGR2 genes) that promote myelin formation around the nerve cells
• Congenital Hypomyelinating Neuropathy has no cure or treatment; the condition is managed symptomatically through medications and physiotherapy
• The prognosis of CHN depends upon its severity. Individuals with milder forms (less neural damage) have a much better prognosis than those with severe forms (severe neural damage)

Who gets Congenital Hypomyelinating Neuropathy? (Age and Sex Distribution)

• Congenital Hypomyelinating Neuropathy is an extremely rare congenital disorder with unknown prevalence. Children are born with this disorder; some symptoms may be noticed at birth and they progress as the child grows
• Both males and females are affected by this disorder
• All races and ethnicities are affected by Congenital Hypomyelinating Neuropathy; no particular predilection is observed

What are the Risk Factors for Congenital Hypomyelinating Neuropathy? (Predisposing Factors)

• Individuals with a family history of Congenital Hypomyelinating Neuropathy are at an increased risk of this disorder
• The mutations that cause CHN can be passed down from family members in an autosomal dominant or autosomal recessive fashion, depending on which gene is mutated
• New mutations can arise during fetal development that can cause CHN

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases ones chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Congenital Hypomyelinating Neuropathy? (Etiology)

The causes of Congenital Hypomyelinating Neuropathy are mutations in the genes MPZ or EGR2 that promote myelin formation in the nervous system.

• The Myelin Protein Zero (MPZ) gene encodes for a protein called P0, which is necessary for the formation and stability of myelin in the peripheral nerves. A mutation in this protein in individuals with Congenital Hypomyelinating Neuropathy causes inefficient surrounding of nerve cells with myelin, leading to weakness and loss of sensations
• The Early Growth Response Gene-2 (EGR2) encodes for a protein that stimulates the production of myelin forming genes. A mutation in EGR2 causes a decrease in the production of myelin around the nerve cells
• The mutations that cause  CHN can be passed down from parents or occur as a random event during fetal development

What are the Signs and Symptoms of Congenital Hypomyelinating Neuropathy?

The signs and symptoms of Congenital Hypomyelinating Neuropathy may not be present at birth, but may develop gradually over the first few months of the child’s life. The common signs and symptoms of Congenital Hypomyelinating Neuropathy include:

• Muscle weakness, low muscle tone
• Absence of reflexes, slow nerve conductions
• Postponed motor development
• Impaired coordination and balance, impaired movements
• Loss of sensations and feelings in the arms and legs
• Respiratory distress
• Stiffened joints
• Foot drop

How is Congenital Hypomyelinating Neuropathy Diagnosed?

A diagnosis of Congenital Hypomyelinating Neuropathy may include:

• A complete physical examination and screening of medical history along with evaluation of family history
• Genetic testing to check if mutations of CHN are present on genes MPZ and ERG2
• Neurological testing (electromyography) to measure the speed of nerve conductions
• Nerve and muscle biopsies to determine myelin levels

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Congenital Hypomyelinating Neuropathy?

Congenital Hypomyelinating Neuropathy is a progressive, irreversible disorder. There may be periods of episodic deterioration of symptoms. The possible complications of Congenital Hypomyelinating Neuropathy may include:

• Swallowing and breathing trouble due to nerve damage
• In babies, delayed crawling, standing, and walking, due to disrupted motor development
• Deformities of the hands and feet from contractures (stiffened joints) due to muscle weakness

How is Congenital Hypomyelinating Neuropathy Treated?

Currently, there is no treatment or cure for Congenital Hypomyelinating Neuropathy. Relief from symptoms, pain, and stress may be ensured by:

• Maintaining movement through physiotherapy
• Using medications to help build muscle strength

How can Congenital Hypomyelinating Neuropathy be Prevented?

• Currently, there are no specific methods or guidelines to prevent Congenital Hypomyelinating Neuropathy, since it is a genetic condition
• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

What is the Prognosis of Congenital Hypomyelinating Neuropathy? (Outcomes/Resolutions)

• There is currently no known cure for Congenital Hypomyelinating Neuropathy
• Individuals with severe forms of CHN may die between 3-7 months
• Individuals with mild forms of CHN may see muscle improvements with proper strength training and physiotherapy
• Certain forms of Congenital Hypomyelinating Neuropathy progress slowly, leading to some individuals being wheelchair bound

Additional and Relevant Useful Information for Congenital Hypomyelinating Neuropathy:

Although, currently, there is no cure for Congenital Hypomyelinating Neuropathy, research into gene therapy is being performed to help correct the genetic events that cause CHN.