Charcot-Marie-Tooth disease type 1E

What it is

From: Orphanet

A rare subtype of CMT1 characterized by a variable clinical presentation. Onset within the first two years of life with a delay in walking is not uncommon; however, onset may occur later. CMT1E is caused by point mutations in the PMP22 (17p12) gene. The disease severity depends on the particular PMP22 mutation, with some cases being very mild and even resembling hereditary neuropathy with liability to pressure palsies, while others having an earlier onset with a more severe phenotype (reminiscent of Dejerine-Sottas syndrome) than that seen in CMT1A, caused by gene duplication. These severe cases may also report deafness and much slower motor nerve conduction velocities compared to CMT1A patients.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Decreased nerve conduction velocity · Very frequent (99-80%)

A reduction in the speed at which electrical signals propagate along the axon of a neuron.

Demyelinating peripheral neuropathy · Very frequent (99-80%)

Demyelinating neuropathy is characterized by slow nerve conduction velocities with reduced amplitudes of sensory/motor nerve conduction and prolonged distal latencies.

Distal lower limb muscle weakness · Very frequent (99-80%)

Reduced strength of the distal musculature of the legs.

Distal sensory impairment · Very frequent (99-80%)

An abnormal reduction in sensation in the distal portions of the extremities.

Gait disturbance · Very frequent (99-80%)

The term gait disturbance can refer to any disruption of the ability to walk.

Sensorineural hearing impairment · Very frequent (99-80%)

A type of hearing impairment in one or both ears related to an abnormal functionality of the cochlear nerve.

Abnormal pupil morphology · Frequent (79-30%)

An abnormality of the pupil.

Abnormality of pain sensation · Frequent (79-30%)

Pain is an unpleasant sensation that can range from mild, localized discomfort to agony, whereby the physical part of pain results from nerve stimulation and is often accompanied by an emotional component. This term groups abnormalities in pain sensation presumed to result from abnormalities related to the specific nerve fibers that carry the pain impulses to the brain.

Acroparesthesia · Frequent (79-30%)

A type of paresthesia (tingling, pins-and-needles, burning or numbness or stiffness) that occurs in the hands and feet and particularly in the fingers and toes.

Areflexia of lower limbs · Frequent (79-30%)

Inability to elicit tendon reflexes in the lower limbs.

Calf muscle hypoplasia · Frequent (79-30%)

Underdevelopment of the muscuklature of the calf.

Distal lower limb amyotrophy · Frequent (79-30%)

Muscular atrophy of distal leg muscles.

Foot dorsiflexor weakness · Frequent (79-30%)

Weakness of the muscles responsible for dorsiflexion of the foot, that is, of the movement of the toes towards the shin. The foot dorsiflexors include the tibialis anterior, the extensor hallucis longus, the extensor digitorum longus, and the peroneus tertius muscles.

Gait disturbance · Frequent (79-30%)

The term gait disturbance can refer to any disruption of the ability to walk.

Other findings in the same source

From: Orphanet

Additional reported features include Hand muscle atrophy (Frequent (79-30%)); Hand muscle weakness (Frequent (79-30%)); Hyporeflexia of lower limbs (Frequent (79-30%)); Hyporeflexia of upper limbs (Frequent (79-30%)); Impaired tactile sensation (Frequent (79-30%)); Impaired temperature sensition (Frequent (79-30%)); Impaired vibration sensation in the lower limbs (Frequent (79-30%)); Peroneal muscle atrophy (Frequent (79-30%)); Peroneal muscle weakness (Frequent (79-30%)); Pes cavus (Frequent (79-30%)). This is a selected summary, not a complete description of the condition.

When it may begin

From: Orphanet

Childhood; Infancy

Inheritance in the source

From: Orphanet

Autosomal dominant

Frequency and the population described

From: Orphanet

Point prevalence: Unknown; Worldwide; Class only.

Understanding the inheritance label

From: MedlinePlus Genetics

An autosomal dominant pattern means that one altered copy of a relevant gene can be sufficient for the condition. Some affected people inherit the change; others have a new change without an affected parent. The precise finding, family history and condition determine what this means for relatives.

Which doctor should you see?

The suggested department for discussing Charcot-Marie-Tooth disease type 1E is Neurology, with a neurologist as the relevant type of clinician. General physician / Family Medicine; paediatrician for children. Referral depends on symptoms.

Additional services that may be relevant, depending on the findings, include: Clinical Genetics.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Which nervous-system findings help explain the symptoms?
• Would an assessment of walking, communication or daily function be helpful?
• Are rehabilitation or other specialist services relevant?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Charcot-Marie-Tooth disease type 1E. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.