Charcot-Marie-Tooth disease type 4B2

What it is

From: Orphanet

A form of Charcot-Marie-Tooth disease type 4 characterized by a severe, early childhood-onset of demyelinating sensorimotor neuropathy, early-onset glaucoma, focally folded myelin sheaths in the peripheral nerves, severely reduced nerve conduction velocities, and the typical CMT phenotype (i.e. distal muscle weakness and atrophy, sensory loss, absence of deep tendon reflexes, and frequent pes cavus). Severe visual impairment leading to visual loss, usually associated with glaucoma, and vocal cord paresis, has also been reported.

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.

Abnormal foot morphology · Very frequent (99-80%)

An abnormality of the skeleton of foot.

Areflexia of lower limbs · Very frequent (99-80%)

Inability to elicit tendon reflexes in the lower limbs.

Decreased distal sensory nerve action potential · Very frequent (99-80%)

A reduction in the amplitude of sensory nerve action potential in distal nerve segments. This feature is measured by nerve conduction studies.

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

Reduced strength of the distal musculature of the legs.

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

Reduced strength of the distal musculature of the arms.

Gait disturbance · Very frequent (99-80%)

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

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

Weakness of the muscles of the legs.

Myelin outfoldings · Very frequent (99-80%)

The presence of excessive redundant myelin in the peripheral nerve sheath.

Poor fine motor coordination · Very frequent (99-80%)

An abnormality of the ability (skills) to perform a precise movement of small muscles with the intent to perform a specific act. Fine motor skills are required to mediate movements of the wrists, hands, fingers, feet, and toes.

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

Inability to elicit tendon reflexes in the upper limbs.

Distal sensory impairment · Frequent (79-30%)

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

Dysphonia · Frequent (79-30%)

Difficulty in speaking due to a physical disorder of the mouth, tongue, throat, or vocal cords. Associated with a known physical or neurological cause.

Glaucoma · Frequent (79-30%)

Glaucoma refers loss of retinal ganglion cells in a characteristic pattern of optic neuropathy usually associated with increased intraocular pressure.

Kyphoscoliosis · Frequent (79-30%)

An abnormal curvature of the spine in both a coronal (lateral) and sagittal (back-to-front) plane.

Other findings in the same source

From: Orphanet

Additional reported features include Pes cavus (Frequent (79-30%)); Proximal muscle weakness in lower limbs (Frequent (79-30%)); Scoliosis (Frequent (79-30%)); Vocal cord paralysis (Frequent (79-30%)); Autistic behavior (Occasional (29-5%)); Buphthalmos (Occasional (29-5%)); Cataract (Occasional (29-5%)); Developmental glaucoma (Occasional (29-5%)); Hand muscle weakness (Occasional (29-5%)); Inability to walk (Occasional (29-5%)). This is a selected summary, not a complete description of the condition.

When it may begin

From: Orphanet

Childhood

Inheritance in the source

From: Orphanet

Autosomal recessive

Understanding the inheritance label

From: MedlinePlus Genetics

An autosomal recessive pattern usually involves disease-causing changes in both copies of a gene. Parents may each carry one altered copy without having the condition themselves. A genetic counsellor can explain carrier testing and reproductive implications using the actual laboratory findings, rather than the condition name alone.

Which doctor should you see?

The suggested department for discussing Charcot-Marie-Tooth disease type 4B2 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 4B2. 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.