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

Biology, Diagnosis, and Reading Your Reports

At a Glance

Hereditary neuropathy with liability to pressure palsies (HNPP) is definitively diagnosed through a genetic test looking for a deletion in the PMP22 gene. Nerve tests like EMGs also reveal a unique diagnostic signature of focal nerve slowing at entrapment sites across the body.

Understanding the biological “why” behind HNPP can transform it from a mysterious set of symptoms into a manageable condition. At its core, HNPP is a problem of dosage: your body is missing a small but vital piece of genetic information, making your nerves’ insulation far more fragile than it should be [1][2].

The Biology of Fragile Myelin

On chromosome 17 (at a location called 17p12), most people have two copies of a gene called PMP22 [1]. This gene provides the blueprints for Peripheral Myelin Protein 22, a building block of myelin—the fatty coating that insulates your nerves and allows electrical signals to travel fast and far [3][4].

  • In HNPP: You have a deletion of one copy of the PMP22 gene [2]. This “haploinsufficiency” means your body only produces half the amount of PMP22 protein it needs [5]. Without enough protein, the myelin develops “leaks” and abnormal, sausage-like swellings along the nerve called tomacula [6][7]. This makes your nerves vulnerable to “short-circuiting” whenever they are squeezed or stretched [6].
  • Contrast with CMT1A: It is helpful to know that HNPP is the “genetic opposite” of Charcot-Marie-Tooth type 1A (CMT1A). CMT1A is caused by a duplication (an extra copy) of the PMP22 gene [1]. Because they share the same genetic root, HNPP is often grouped under the broader Charcot-Marie-Tooth (CMT) family of neuropathies. This is highly valuable to know when searching for support groups, advocacy networks, or multidisciplinary clinics [1][8].

Inheritance and Family Planning

Because HNPP is a genetic disorder, it is natural to wonder about your family. HNPP follows an autosomal dominant inheritance pattern [9].

  • This means you only need one deleted copy of the gene (inherited from one parent) to have the condition.
  • If you have HNPP, there is a 50% chance of passing the genetic deletion to each child you have [10].
  • It is strongly recommended that you speak with a genetic counselor. They can help you navigate family planning, testing for your children, and explaining the condition to relatives who might have experienced unexplained palsies in the past [11].

Empowering Yourself: Reading Your Reports

Before a genetic test confirms the diagnosis, doctors often use Nerve Conduction Studies (NCS) and Electromyography (EMG) to look for the “fingerprints” of HNPP. When you look at your lab results, you are looking for a specific signature that sets HNPP apart from other conditions [9].

The HNPP “Signature”

In a typical NCS/EMG report for HNPP, you will often see these three findings:

  1. Focal Slowing at Entrapment Sites: This is the most important clue. It means the electrical signal slows down significantly as it passes through natural narrowings in your body, like the wrist (carpal tunnel) or the elbow [9][12].
  2. Global Increase in Distal Motor Latencies: “Distal motor latency” refers to the time it takes for a nerve signal to reach a muscle at the end of a limb (like your hand or foot). In HNPP, these times are often longer than normal throughout the body, even in nerves that don’t feel “numb” [9][13].
  3. Reduced Sensory Velocities: The signals that carry sensation (touch, temperature) often move slower than they should across many different nerves [9][14].

Navigating Misdiagnosis

Because HNPP involves “attacks” of weakness and numbness, it is frequently mistaken for other conditions:

  • Multiple Sclerosis (MS): Because both involve myelin damage and episodic symptoms, HNPP is often misdiagnosed as MS. However, MS affects the central nervous system (brain/spine), while HNPP affects only the peripheral nerves [15][16].
  • CIDP (Chronic Inflammatory Demyelinating Polyneuropathy): This is an autoimmune condition where the body attacks its own myelin. Unlike HNPP, it is treated with immune-suppressing drugs, which are not effective for HNPP [16][17].
  • Isolated Carpal Tunnel Syndrome: Many HNPP patients are told they simply have carpal tunnel. The difference is that in HNPP, the “slowing” is found in multiple nerves all over the body, not just the wrist [9][18].

The Gold Standard: Genetic Testing

While EMG and NCS are excellent tools, genetic testing is the only way to definitively diagnose HNPP [17][11]. A simple blood or saliva test looks for the missing copy of the PMP22 gene [2]. About 80% of patients will have this large deletion [19]. For the remaining patients who have symptoms but no deletion, doctors may look for smaller “point mutations” (typos) within the gene itself [19][20]. Confirmatory genetic testing is crucial because it rules out other conditions and gives certainty to your medical journey [10][11].

Common questions in this guide

How is HNPP inherited?
HNPP follows an autosomal dominant inheritance pattern. This means that if you have the condition, there is a 50 percent chance of passing the genetic deletion to each of your children.
What does focal slowing mean on my EMG report?
Focal slowing means the electrical signal in your nerve slows down significantly as it passes through natural narrowings in your body, like the wrist or elbow. This widespread slowing is a key diagnostic clue for HNPP.
How is HNPP different from Multiple Sclerosis (MS)?
While both conditions involve myelin damage and episodic symptoms, HNPP only affects the peripheral nerves outside the brain and spinal cord. Multiple Sclerosis, on the other hand, affects the central nervous system.
Why is HNPP often misdiagnosed as carpal tunnel syndrome?
Both conditions can cause numbness or weakness in the hands. However, in isolated carpal tunnel syndrome, nerve slowing only happens at the wrist, whereas people with HNPP usually show nerve slowing in multiple locations throughout the body.
What happens if my PMP22 genetic test is negative but I have HNPP symptoms?
About 80 percent of people with HNPP have a large deletion of the PMP22 gene. If you test negative for the deletion but still have symptoms, your doctor can order further testing to look for smaller point mutations, or 'typos', within the gene itself.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.My report mentions 'focal slowing'—is this occurring at sites other than just my wrist?
  2. 2.If my PMP22 deletion test comes back negative, will we pursue testing for PMP22 point mutations?
  3. 3.Can you refer me to a genetic counselor to discuss the implications of my HNPP diagnosis for my family?
  4. 4.How do my results help rule out inflammatory conditions like CIDP or central nervous system disorders like MS?

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 HNPP biology and diagnostic testing for educational purposes. Always consult a neurologist or genetic counselor to interpret your specific EMG results or genetic tests.

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