Article Summary
A single-copy deletion of the PMP22 gene in the 17p12 region causes an inherited peripheral nerve disorder. Its formal name is Hereditary Neuropathy with Liability to Pressure Palsies (HNPP). When the same 17p12 gene is instead duplicated, a different disease results: Charcot-Marie-Tooth disease type 1A (CMT1A). Deletion and duplication are opposite genetic changes, and they produce different symptom patterns. HNPP is an episodic nerve disorder in which pressure on a limb triggers numbness or weakness; most cases are mild to moderate. This article explains the difference between the deletion (HNPP) and duplication (CMT1A) forms, their causes, symptoms, diagnosis, and everyday precautions. We also review how this condition relates to NIPT during pregnancy, based on information from public health authorities and medical societies.
What You’ll Learn in This Article
- Why “17p12 deletion” and “Charcot-Marie-Tooth disease type 1A” are both mentioned together, and the exact relationship between them
- How symptoms differ between the deletion (HNPP) and duplication (CMT1A) forms
- The tests used for diagnosis, and everyday precautions to reduce nerve pressure
- How much of this condition NIPT can detect during pregnancy, and its relationship to confirmatory testing
Introduction: Why Two Disease Names Appear Together
You may have seen both “17p12 deletion” and “Charcot-Marie-Tooth disease type 1A” listed together on a checkup or genetic test report. If the unfamiliar terms left you confused, you are not alone. In fact, these are two separate diseases. They involve the same gene region, but the direction of the genetic change is opposite.
The short arm of chromosome 17, region 12 (17p12), contains the PMP22 gene, which builds the myelin sheath covering peripheral nerves. When this region is missing (deleted), the result is Hereditary Neuropathy with Liability to Pressure Palsies (HNPP). When it is instead duplicated, the result is Charcot-Marie-Tooth disease type 1A (CMT1A).
This article is written for readers who searched for “17p12 deletion” specifically. We focus first on HNPP, the deletion-related disease, and then clarify how it differs from the often-confused CMT1A. Please read through in order.
1. Cause: The PMP22 Gene and How the Deletion Occurs
First, let’s look at why this condition occurs, starting at the genetic level.
The PMP22 Gene and Peripheral Nerve Myelin
PMP22 (Peripheral Myelin Protein 22) is a gene that produces a major component of the myelin sheath, the protective covering around peripheral nerves. Under normal circumstances, a person carries two copies of this gene, one inherited from each parent.
Having both copies present is considered important for normal nerve signal transmission. When one copy is missing, or conversely when a third copy is added, the function of the myelin sheath becomes uneven.
Why the Deletion Happens
About 80% of HNPP cases arise from “unequal crossing-over,” an event that occurs during the formation of sperm or egg cells (meiosis). Repeat sequences within the 17p12 region recombine unevenly, causing an entire region of roughly 1.5 Mb, including the PMP22 gene, to be deleted. The remaining approximately 20% of cases result from other genetic changes that do not involve a deletion, such as a point mutation within the PMP22 gene itself.
This unequal crossing-over occurs by chance during the formation of reproductive cells, and nothing about lifestyle or behavior during pregnancy causes it. Please know first that there is absolutely no reason to blame yourself.
2. The Difference Between HNPP (Deletion) and CMT1A (Duplication)
Even though the same PMP22 gene and the same 17p12 region are involved, the deletion and duplication forms present very differently. The table below summarizes the key differences.
| Comparison | HNPP (17p12 deletion) | CMT1A (17p12 duplication) |
|---|---|---|
| Genetic change | One copy of the region containing PMP22 is deleted | One copy of the region containing PMP22 is duplicated |
| Course of symptoms | Sudden episodes triggered by pressure, most of which resolve on their own | Slowly progressive weakness in the hands and feet |
| Typical symptoms | Foot drop from peroneal nerve palsy, carpal tunnel syndrome, ulnar nerve palsy | High arches, foot drop, weakness and wasting of distal muscles, sensory disturbance |
| Typical age of onset | Teens to twenties | Ages 5 to 25 |
| Approximate frequency | About 2 to 5 per 100,000 people | About 50% of all CMT cases |
In short, HNPP is a condition that makes nerves “more vulnerable to pressure,” while CMT1A is a condition that “progresses gradually over time.” Diagnostic reports and online information sometimes mix the two together. Always check whether your test result specifically states “deletion” or “duplication.”
In rare cases, neither a deletion nor a duplication occurs; instead, the PMP22 region gains a third extra copy, known as a “triplication.” This produces a more severe condition than CMT1A called Yuan-Harel-Lupski syndrome (YUHAL). For more on the duplication form, see our article on 17p12 duplication syndrome.
3. Main Symptoms: Temporary Nerve Dysfunction from Pressure
The defining feature of HNPP is that everyday, minor pressure can trigger symptoms. Sitting cross-legged for a long time, sleeping on an arm, or carrying a heavy bag on one shoulder for an extended period can all act as triggers.
Nerves Prone to Pressure and Their Symptoms
Symptoms tend to appear at nerves in parts of the body that are especially exposed to pressure.
- Peroneal nerve palsy: Crossing your legs, for example, can trigger “foot drop,” in which you can no longer lift your foot at the ankle.
- Carpal tunnel syndrome: Pressure on the wrist can cause numbness or reduced sensation from the thumb to the ring finger.
- Ulnar nerve palsy: Keeping the elbow bent for a long time can cause numbness or weakness on the little-finger side of the hand.
- Brachial plexus injury: Carrying a heavy backpack for a long period can make it harder to use the entire arm with normal strength.
Symptom duration varies widely, from a few minutes to several months. In most cases, removing the source of pressure leads to natural recovery within a few weeks to a few months, though repeated pressure can prolong recovery time.
Age of Onset and Individual Variation
The first symptoms most often appear in the teens to twenties. That said, please know that some people who carry the gene change never develop any symptoms in their lifetime. The severity of symptoms can vary considerably, even among members of the same family.
4. Inheritance Pattern: Implications for Future Children
HNPP follows an autosomal dominant inheritance pattern. If either parent carries the PMP22 deletion, each child has roughly a one-in-two chance of inheriting it, regardless of sex.
That said, even when no one else in the family has similar symptoms, the deletion can also arise newly as a spontaneous mutation. Whether the condition is actually inherited depends on the specific family. To find out the likelihood that it will be passed to a future child, please consult a certified clinical geneticist or genetic counselor through individualized genetic counseling (Japanese-language resource).
In my own work advising patients about NIPT, I meet many families facing this exact question. I often hear people say they want to know first “whether this is inherited from a parent or occurred spontaneously.” I have come to feel that it matters to look not only at the test result itself, but also at the full family history.
5. How It Is Diagnosed
HNPP is diagnosed by reviewing the course of symptoms and combining nerve function testing with genetic testing.
Nerve Conduction Study and Electromyography
A nerve conduction study (NCS) applies a small electrical stimulus to a nerve and measures how fast the signal travels. Electromyography (EMG) examines the electrical activity of muscles. Together, these two tests provide important diagnostic clues. A characteristic finding is slowed conduction velocity specifically at sites prone to pressure.
Genetic Testing
A definitive diagnosis relies on genetic testing that measures the copy number of the PMP22 gene. Common methods include MLPA (multiplex ligation-dependent probe amplification), FISH (fluorescence in situ hybridization), and chromosomal microarray analysis (CMA). These tests determine whether the copy number has decreased to one (deletion), remains at two, or has increased (duplication or triplication).
Because symptoms alone can make it difficult to distinguish deletion from duplication, confirming the diagnosis through genetic testing also helps guide treatment decisions.
6. Treatment and Everyday Adjustments
No treatment currently exists that corrects the underlying PMP22 gene deletion itself. Management therefore centers on avoiding pressure and treating symptoms when they occur.
Lifestyle Adjustments to Avoid Pressure
The single most important step for prevention is avoiding movements and positions that put sustained pressure on nerves.
- Avoid sitting cross-legged or kneeling with your weight on your legs for long periods.
- Choose a backpack that distributes weight across both shoulders, rather than carrying a heavy bag on one shoulder for a long time.
- Avoid resting your weight on your elbows or sleeping with your arm under your head.
Physical Therapy, Braces, and Rare Surgical Options
When foot drop persists, an ankle-foot orthosis (AFO) may be used to assist walking. Physical therapy is also commonly used alongside bracing to help maintain muscle strength and joint flexibility. Surgical correction is considered only in cases with significant skeletal deformity that interferes with daily life.
7. Outlook: Maintaining Quality of Life
HNPP is not a progressive disease, and many people who learn to avoid the triggers of pressure are able to maintain a stable quality of life over the long term. In practice, most patients continue their usual daily activities and work.
That said, some reports suggest that symptoms are more likely to persist in cases with repeated pressure episodes or in cases caused by a point mutation rather than a deletion. Regular follow-up with a neurologist is important to monitor the course of the condition.
8. Relationship to NIPT During Pregnancy
The basic NIPT panel, which screens for trisomy 21, 18, and 13, does not cover small chromosomal deletions or duplications such as 17p12. Some testing plans offer an optional expanded panel that includes microdeletion and microduplication syndromes, but the specific conditions covered vary by testing facility and plan.
To find out whether the plan you are considering covers the 17p12 region, please contact the testing facility directly. You may also find it helpful to read our article on how NIPT detects microdeletion syndromes (Japanese-language resource) and our overview of microdeletion and microduplication conditions.
One more important point to understand is that NIPT is strictly a non-definitive screening test. If a screening result is positive, a confirmatory diagnosis is made through amniocentesis. That confirmatory process examines the sample obtained to measure the copy number of the PMP22 gene, using methods such as MLPA or chromosomal microarray analysis (CMA). It is also worth knowing that a conventional microscope-based karyotype analysis (G-banding) alone cannot detect a change of this size in this region.
When researching this condition, we looked for recent posts on X (formerly Twitter) describing real first-hand experiences in Japan, but found none in the recent period. Because this is a rare condition, a scarcity of first-hand accounts is expected. In their place, this article draws on information from the Japan-based Ministry of Health, Labour and Welfare Intractable Disease Information Center and MGeND/MGenReviews, along with other public health authorities and academic societies.
9. A Message to Families
Seeing the term “Charcot-Marie-Tooth disease type 1A” may lead some readers to assume they are facing a progressive disease and feel anxious. However, the deletion form, HNPP, follows a different course than the duplication form, CMT1A, and it is a condition that can be managed calmly by avoiding pressure triggers.
When ongoing medical visits and brace management are needed over the long term, the burden on the family can grow. Work with your medical team and support organizations to build a sustainable routine that does not push you or your family too hard.
In genetic counseling settings, we hear the question “will this also be passed to my next child?” very often. In most cases, an accurate test result combined with a review of the family history makes the outlook much clearer. Please don’t carry this alone; reach out to a specialist.
We also welcome inquiries by phone. Please feel free to call 0120-169-629 (Japan) with any questions.
Frequently Asked Questions
Are 17p12 deletion syndrome and Charcot-Marie-Tooth disease type 1A (CMT1A) the same disease?
They involve the same PMP22 gene and the same 17p12 region, but they are different diseases. The deletion form causes Hereditary Neuropathy with Liability to Pressure Palsies (HNPP), while the duplication form causes CMT1A, and the two follow a different symptom course.
What symptoms does HNPP cause?
Positions that press on a nerve, such as sitting cross-legged or sleeping on an arm, can trigger sudden numbness or weakness in the hands or feet. Foot drop and carpal tunnel syndrome are typical examples. Most episodes resolve on their own within a few weeks to a few months.
Can this be passed on to a child?
Because HNPP follows an autosomal dominant pattern, if a parent carries the deletion, each child has roughly a one-in-two chance of inheriting it, regardless of sex. Even without a family history, the deletion can also occur as a new, spontaneous mutation. Please confirm your specific situation through genetic counseling.
Can this condition be detected by NIPT during pregnancy?
It is not covered by the basic NIPT panel that screens for trisomy 21, 18, and 13. Some plans offer an optional test that covers microdeletion and microduplication conditions, but coverage varies by facility, so please confirm directly with the testing facility you are considering. If a screening result is positive, a confirmatory test such as amniocentesis is required.
What tests provide a definitive diagnosis?
A definitive diagnosis combines nerve conduction studies and electromyography with genetic testing. Genetic testing methods such as MLPA, FISH, and chromosomal microarray analysis (CMA) are used to measure the copy number of the PMP22 gene.
Is Charcot-Marie-Tooth disease a Japanese government-designated intractable disease?
Charcot-Marie-Tooth disease itself is designated as Intractable Disease No. 10 by Japan’s Ministry of Health, Labour and Welfare. Whether HNPP specifically qualifies for this designation should be confirmed with your physician or your local government office.
Medical Supervision: Hiroshi Oka / Director-General, Hiro Clinic (Fukubikai Medical Corporation), Lab Director. Graduate of Keio University School of Medicine. Passed the national medical licensing examinations in both Japan and the United States, and holds a Ph.D. in Medicine. One of a small number of physicians in Japan certified as a Lab Director. Author of “The First Book to Read When You Learn You’re Pregnant.” This article was prepared with attention to Japan’s medical advertising guidelines, referencing information from public health authorities and academic societies. Cited figures may vary across sources; please consult your physician for final decisions on diagnosis and treatment.
References (Japanese-language sources): Hereditary Neuropathy with Liability to Pressure Palsies (HNPP) | MGenReviews (Japan Institute for Health Security) / Charcot-Marie-Tooth disease (Designated Intractable Disease No. 10) | Intractable Disease Information Center / Charcot-Marie-Tooth (CMT) Hereditary Neuropathy Overview | GeneReviews Japan / Certification (Clinical Genetics Specialists and Certified Genetic Counselors) | Japan Society of Human Genetics
日本皮膚科学会 皮膚科専門医／日本医師会 産業医／東京衛生検査所 指導監督医
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