Why Is Genetic Testing Needed to Confirm an HNPP Diagnosis?

Electrodiagnostic testing—often referred to generally as an EMG and nerve conduction study—can show where your nerves are struggling, but it cannot definitively prove why. Because the nerve slowing seen in Hereditary Neuropathy with Liability to Pressure Palsies (HNPP) can mimic common conditions like carpal tunnel syndrome or an autoimmune disease called CIDP, a genetic test is the gold standard for confirming the diagnosis. Confirming the genetic cause helps ensure you get the right advice, provides clarity for your family, and protects you from inappropriate treatments.

What Nerve Tests Can (and Cannot) Tell You

When you undergo electrodiagnostic testing, the doctor uses nerve conduction studies (NCS) to measure how fast electrical signals travel through your nerves, and an electromyogram (EMG) to evaluate muscle electrical activity. In HNPP, the protective coating of the nerve (myelin) is fragile, making nerves vulnerable at natural pinch points like the wrist or the elbow ^[1][2].

However, finding focal slowing (a delay in the nerve signal at a single pinch point) is incredibly common in the general population. If a doctor only tests your symptomatic arm, the results might look identical to standard carpal tunnel syndrome or cubital tunnel syndrome ^[2][3].

Testing becomes highly suspicious for HNPP when it reveals a multifocal pattern—meaning there is nerve slowing at multiple compression sites, even in nerves where you currently have no symptoms ^[4][2]. Yet, even this broader pattern is just a strong clue. It takes a genetic test to definitively identify the root cause ^[3].

Why Confirming the Diagnosis Matters

Without genetic confirmation, the symptoms and test results of HNPP can sometimes be mistaken for other conditions. Getting the diagnosis right changes your care plan.

• Differentiating from CIDP: HNPP can cause conduction block (where the nerve signal is severely delayed or stopped), a feature it shares with Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) ^[5][6]. CIDP is an autoimmune condition typically treated with immune therapies like IVIG or steroids. While uncommon, there are documented cases of patients with unrecognized HNPP receiving ineffective immune treatments for presumed CIDP before a genetic test corrected the diagnosis ^[7][8]. (Note: Never stop prescribed immune therapies without first consulting your neurologist, as CIDP requires appropriate and often urgent treatment).
• Making Informed Surgical Decisions: If your nerve slowing is assumed to be standard carpal tunnel syndrome, a doctor might recommend surgical decompression. People with HNPP can develop standard nerve entrapments and some do benefit from carpal tunnel release. However, surgical outcomes in HNPP patients are highly variable, and decompression is not a cure for the underlying fragility of the nerve ^[9][10]. Genetic confirmation allows you and your surgeon to carefully weigh the risks, benefits, and alternatives before operating ^[11].

What the Genetic Test Looks For

To confirm HNPP, your doctor will order a genetic test (usually a simple blood draw or cheek swab) specifically evaluating the PMP22 gene.

• The PMP22 Deletion: In roughly 80% of confirmed cases, HNPP is caused by a missing piece of genetic code (a deletion) on chromosome 17 that includes the PMP22 gene ^[12][13]. If this deletion is found in the right clinical context, the genetic cause of your HNPP is strongly confirmed ^[14].
• PMP22 Sequencing: A meaningful minority of people with HNPP do not have the full deletion, but rather a sequence variant (a “typo” in the genetic code) within the gene. If your initial deletion test is negative but your doctor still strongly suspects HNPP, they may order gene sequencing to look for these specific variants ^[15][16].

The Role of Genetic Counseling

Because HNPP is an autosomal dominant condition, a person with the condition has a 50% chance of passing the genetic variant to each of their children. However, symptoms can vary widely—even within the same family, some relatives may be entirely asymptomatic ^[12][17].

Before and after genetic testing, it is highly recommended to speak with a genetic counselor. They can help you understand what a positive, negative, or “uncertain” result means for you, how to communicate risks to your blood relatives, and the practical implications for family planning and insurance.

Ultimately, a confirmed diagnosis shifts your care team’s focus to what actually helps: protecting your nerves from pressure. This includes practical lifestyle adjustments like avoiding crossing your legs, minimizing repetitive motions, using padded elbow rests, and working with occupational therapy to prevent future palsies ^[14][11].