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PubMed This is a summary of 20 peer-reviewed journal articles Updated
Neurology

Navigating the Diagnostic Process: Tests and Results

At a Glance

The diagnosis of genetic peripheral neuropathy involves electrical tests (EMG and NCS) to evaluate nerve function, followed by genetic testing to identify the specific DNA mutation. A clear understanding of your nerve signal speed and genetic results helps confirm the exact neuropathy subtype.

The journey to a diagnosis for genetic peripheral neuropathy usually involves two major steps: “listening” to the nerves’ electrical signals and “reading” your genetic code. These tests help doctors distinguish between damage to the nerve’s insulation (myelin) and damage to the nerve’s inner wire (axon) [1][2].

Electrical Testing: The EMG and NCS

Before genetic testing, doctors often perform a Nerve Conduction Study (NCS) and an Electromyography (EMG).

  • Nerve Conduction Study (NCS): This test measures how fast and how strong electrical signals travel through your nerves [3].
    • Uniform Slowing: If the signal is very slow but consistent across all nerves, it typically points to a genetic condition like CMT1 [1].
    • Patchy/Focal Slowing: If the slowing happens only in specific spots (called a conduction block), it often suggests an acquired condition like CIDP rather than a genetic one [4][5].
    • Low Amplitudes: If the signals are fast enough but very “weak” or small, it suggests axonal damage, common in CMT2 [1][6].
  • Electromyography (EMG): A tiny needle electrode is used to listen to the electrical activity in your muscles. This helps determine if muscle weakness is caused by the nerve failing to “talk” to the muscle [7].

Genetic Testing: Reading the Blueprint

Genetic testing is the only way to confirm a specific subtype. Doctors usually start with a gene panel, which is a targeted search through the most common genes known to cause neuropathy (like PMP22, MFN2, or GJB1) [8][9].

If a panel comes back empty, a doctor may order Whole Exome Sequencing (WES), which looks at all the “coding” parts of your DNA [10]. It is important to remember that a “negative” test does not always mean you don’t have a genetic condition—it may just mean science hasn’t discovered your specific gene mutation yet [11].

Understanding Your Results

Genetic reports can be confusing. You will likely see one of three results for various genes:

  1. Pathogenic: This is a “positive” result. A mutation was found that is known to cause the disease [12].
  2. Benign: This is a “negative” result. A variation was found, but it is considered a normal human difference that doesn’t cause disease [13].
  3. Variant of Uncertain Significance (VUS): This is the “maybe” result. A change was found in your DNA, but scientists don’t yet have enough data to know if it causes disease or is harmless [13][14]. Over time, as more people are tested, a VUS may be reclassified. It is important to know that doctors generally will not make major treatment decisions based solely on a VUS until science completely proves it is pathogenic [15].

How is it Passed Down? Inheritance Patterns

When you meet with a Genetic Counselor, they will map out your family history to understand how the disease is inherited:

  • Autosomal Dominant: You only need one copy of the mutated gene to get the disease. If you have it, each of your children has a 50% chance of inheriting it. This is the most common pattern for CMT1A [16].
  • Autosomal Recessive: You need two copies (one from each parent). Parents are usually “carriers” without symptoms.
  • X-Linked: The mutation is on the X chromosome, meaning it often affects men more severely than women [17].

Completeness Checklist for Lab Reports

When you receive your reports, ensure they include these key details for your records:

  • For NCS Reports: Ask your doctor to explain your Nerve Conduction Velocity (NCV) (which measures the speed of the signal) and your CMAP amplitudes (which measures the strength of the muscle response). Knowing if your primary issue is “speed” or “strength” helps confirm your subtype [3][18].
  • For Genetic Reports: The specific gene name, the variant (the “address” of the mutation, e.g., c.123G>A), and the classification (Pathogenic, Benign, or VUS) [13][19].
  • Family Mapping: A record of which family members have similar symptoms, which helps geneticists interpret your results [20].

Common questions in this guide

What is the difference between an EMG and an NCS for neuropathy?
A Nerve Conduction Study (NCS) measures how fast and strong electrical signals travel through your nerves. An Electromyography (EMG) uses a tiny needle to evaluate the electrical activity in your muscles to see if the nerve is successfully communicating with them.
What does uniform slowing mean on a nerve conduction study?
Uniform slowing means the electrical signal travels slowly but consistently across all tested nerves. This typically points to a genetic nerve condition, like Charcot-Marie-Tooth disease type 1 (CMT1), because it indicates the insulating myelin on the nerves is broadly affected.
What is a Variant of Uncertain Significance (VUS) on a genetic test report?
A VUS means a change was found in your DNA, but scientists do not yet have enough data to know if it causes disease or is simply a harmless variation. Doctors generally will not base major treatment decisions on a VUS until more research confirms its effect.
Why might my genetic test for neuropathy be negative if I have symptoms?
A negative genetic test does not always mean you do not have a genetic neuropathy. It often just means that science has not yet discovered the specific gene mutation responsible for your condition, and further testing like Whole Exome Sequencing may be an option.
What is Whole Exome Sequencing (WES) for neuropathy?
If a standard gene panel does not find a known mutation, your doctor may order WES. This is a comprehensive genetic test that looks at all the protein-coding parts of your DNA to search for rarer or newly discovered genetic causes of neuropathy.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.Was my Nerve Conduction Velocity (NCV) above or below 38 m/s, and what does that tell us about my subtype?
  2. 2.Does my report show 'conduction block' (patchy damage) or 'uniform slowing'?
  3. 3.Which specific genes were included in my testing panel, and were common mutations like the PMP22 duplication ruled out first?
  4. 4.If a VUS was found, can we test my siblings or parents to see if they carry the same genetic variant?
  5. 5.Given my symptoms, if my genetic test was negative, should we consider Whole Exome Sequencing (WES) or a follow-up in a few years?

Questions For You

Tap a prompt to share your answer — we'll use it plus this page's context to start a tailored conversation.

References

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This page explains diagnostic tests for genetic peripheral neuropathy for educational purposes only. Always discuss your EMG, NCS, and genetic test results directly with your neurologist or genetic counselor to understand what they mean for your care.

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