Article Summary
A single extra copy of the PMP22 gene in the 17p12 region causes Charcot-Marie-Tooth disease type 1A (CMT1A). It is the most common form of CMT, accounting for roughly 40-50% of all CMT cases. A “deletion” of the same 17p12 region causes a different condition, hereditary neuropathy with liability to pressure palsies (HNPP). Duplication and deletion are opposite genetic changes with very different clinical courses. CMT1A is a slowly progressive peripheral neuropathy in which strength in the feet and hands declines gradually. Progression is gradual, and life expectancy is generally not affected. This article explains the differences between duplication (CMT1A) and deletion (HNPP), the causes, symptoms, diagnosis, and everyday precautions, and also summarizes how this condition relates to prenatal NIPT based on information from public health authorities and medical societies.
What You’ll Learn in This Article
- Why “17p12 duplication” and “Charcot-Marie-Tooth disease type 1A” are used to refer to the same condition
- The differences between duplication (CMT1A), deletion (HNPP), and the easily confused 17p11.2 duplication (Potocki-Lupski syndrome)
- The tests used for diagnosis, and everyday posture and movement points to keep in mind
- How much of this condition prenatal NIPT can detect, and its relationship to a definitive diagnosis
Introduction: Why So Many Similar Names Appear
Genetic test results sometimes list both “17p12 duplication” and “Charcot-Marie-Tooth disease type 1A” together. With so many similarly named conditions, it is easy to feel confused. In fact, the direction of the genetic change determines which condition results, and the two outcomes are completely different.
The short arm region 17p12 of chromosome 17 contains the PMP22 gene, which helps build the myelin sheath that insulates peripheral nerves. When this region is duplicated, the result is Charcot-Marie-Tooth disease type 1A (CMT1A). When it is instead missing (deleted), the result is a different condition called hereditary neuropathy with liability to pressure palsies (HNPP).
This article is written for readers who arrived here searching for “17p12 duplication.” We first explain CMT1A in detail, then clarify how it differs from the easily confused HNPP and 17p11.2 duplication. Please read through in order.
1. Cause: The PMP22 Gene and How Duplication Occurs
Let’s start by looking at why this condition occurs, at the genetic level.
The PMP22 Gene and the Peripheral Nerve Myelin Sheath
PMP22 (peripheral myelin protein 22) is a gene that produces a major component of the myelin sheath covering peripheral nerves. People normally carry two copies of this gene, one inherited from each parent.
Having exactly these two copies is thought to be important for normal nerve signal transmission. When an extra copy brings the total to three, or when one copy is lost, the function of the myelin sheath becomes uneven.
Why the Duplication Occurs
Most cases of CMT1A result from “unequal crossing over” during the formation of sperm or eggs (meiosis). Repeated sequences within the 17p12 region recombine unevenly, duplicating an approximately 1.5 Mb region that includes the PMP22 gene. A small number of cases instead result from other gene changes that do not involve duplication, such as point mutations within the PMP22 gene itself.
This unequal crossing over is a chance event that occurs 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. CMT1A (Duplication) vs. HNPP (Deletion), and Other Similarly Named Conditions
Although the same PMP22 gene and the same 17p12 region are involved, duplication and deletion produce very different symptoms. The table below summarizes the differences.
| Comparison | CMT1A (17p12 duplication) | HNPP (17p12 deletion) |
|---|---|---|
| Genetic change | One extra copy of the region containing PMP22 | One missing copy of the region containing PMP22 |
| Clinical course | Slowly progressive weakening of the feet and hands over time | Episodic, often triggered by pressure on a nerve, usually resolving on its own |
| Typical symptoms | Pes cavus and foot drop, weakness and wasting of distal muscles, sensory disturbance | Foot drop from peroneal nerve palsy, carpal tunnel syndrome, ulnar nerve palsy |
| Typical age of onset | 5 to 25 years old | Teens to 20s |
| Nerve conduction findings | Conduction velocity is slowed uniformly, regardless of the site of compression | Conduction velocity is slowed only at sites prone to compression |
In short, CMT1A is a condition that “progresses gradually,” while HNPP is a condition that “becomes vulnerable to pressure.” Reports and online information sometimes mix the two together, so always check whether your test result specifically states “duplication” or “deletion.”
In rare cases, the PMP22 region increases to three extra copies, known as a “triplication,” rather than a simple duplication or deletion. This tends to cause more severe symptoms than CMT1A and is treated as a separate condition called Yuan-Harel-Lupski syndrome (YUHAL). For details on the deletion side, please also see our article on 17p12 deletion syndrome.
There is another condition that is often confused with this one because of its similar name: Potocki-Lupski syndrome, which is caused by duplication of the 17p11.2 region. 17p12 and 17p11.2 are both located on the short arm of chromosome 17, but they involve a completely different set of genes at a different location. Potocki-Lupski syndrome mainly involves developmental delay, intellectual disability, and behavioral traits associated with autism spectrum disorder, and its clinical course is very different from the peripheral nerve symptoms of CMT1A. See the article below for more detail.
There is also a condition caused by duplication of the 17p13.3 region, near the other end of chromosome 17. This condition is likewise centered on developmental effects and is different from 17p12 duplication (CMT1A). Please check the article below as well.
3. Main Symptoms: A Slowly Progressive Peripheral Neuropathy
The defining feature of CMT1A is that symptoms begin at the extremities, such as the toes, and gradually spread from there. Sudden worsening is uncommon; progression is usually gradual and unfolds over several years.
Typical Symptoms
How symptoms appear varies from person to person, but several features are commonly seen.
- Foot drop and pes cavus: Difficulty lifting the ankle (foot drop) and a high foot arch (pes cavus) are commonly seen.
- Weakness in distal muscles: Strength declines first in muscles near the extremities, such as the ankles and fingers.
- Muscle wasting: Thinning of the calf muscles, sometimes described as an “inverted champagne bottle” leg shape, is a characteristic sign.
- Sensory disturbance and reduced reflexes: Vibration and position sense may become dulled, and tendon reflexes may weaken.
CMT1A is often described as painless, but in practice some people do report neuropathic pain. The intensity of numbness and the speed of progression can vary considerably even among members of the same family.
Age of Onset and Pace of Progression
The first symptoms most often appear between the ages of 5 and 25. That said, some people are not diagnosed until after age 60. The severity of symptoms can vary considerably even within the same family.
4. Inheritance Pattern: What It Means for Future Children
CMT1A is inherited in an autosomal dominant pattern. If either parent carries the PMP22 duplication, there is roughly a 50% chance of passing it on to each child, regardless of the child’s sex.
Even so, in some cases a new duplication arises spontaneously with no affected relatives in the family history. Whether it is actually inherited, and at what likelihood, differs from family to family. To understand the probability for a future child, please consult a clinical geneticist or certified genetic counselor through individualized genetic counseling (Japanese-language resource).
In my own work counseling families about NIPT, I meet many parents who first want to know whether a condition was inherited from a parent or arose spontaneously. I have found that it matters to look not only at the test result itself, but also at the full family history.
5. How CMT1A Is Diagnosed
CMT1A is diagnosed by reviewing the clinical course together with a combination of nerve function testing and genetic testing.
Nerve Conduction Studies and Electromyography
A nerve conduction study (NCS) applies a small electrical stimulus to a nerve and measures how quickly the signal travels. Electromyography (EMG) examines the electrical activity of muscles. A hallmark of CMT1A is that conduction velocity is slowed uniformly throughout the nerve (typically below 38 m/s), regardless of where compression occurs. This uniform slowing is a key clue that distinguishes it from HNPP, where slowing is limited to sites prone to compression.
Genetic Testing
A definitive diagnosis relies on genetic testing that measures the copy number of the PMP22 gene. Common methods include MLPA, FISH, and chromosomal microarray analysis (CMA). These tests determine whether the gene is present at one copy, the usual two copies, or an increased number (duplication or triplication).
Because symptoms alone can make it difficult to distinguish duplication from deletion, confirming the diagnosis with genetic testing also helps guide treatment decisions.
6. Treatment and Everyday Management
At present, there is no treatment that cures the underlying PMP22 duplication itself. Care therefore centers on supportive treatment while monitoring how symptoms progress.
Rehabilitation and Orthotics
For persistent foot drop, an ankle-foot orthosis (AFO) may be used to assist walking. Physical therapy and occupational therapy are also commonly used alongside orthotics to maintain muscle strength and joint flexibility. Surgical correction is considered only in cases where skeletal deformity is severe enough to interfere with daily life.
Everyday Precautions
There is no definitive way to slow the progression of CMT1A, but everyday adjustments can reduce the risk of falls and similar problems.
- Identify fall risks in advance, such as uneven steps or slippery flooring.
- Choose well-fitting shoes or orthotics, and have your condition checked regularly by an orthopedist or neurologist.
- Talk with your doctor before taking any medication with known neurotoxic effects, since these can place extra strain on peripheral nerves.
7. Prognosis: Long-Term Outlook and Support
CMT1A is progressive, but the pace is gradual, and life expectancy is generally not shortened. Many patients continue with ordinary daily life and work, with the help of orthotics and other support as needed.
At the same time, muscle weakness can advance with age, and some people eventually need assistance with daily activities. Regular follow-up with a neurologist to monitor the condition is important.
8. Relationship to Prenatal NIPT
The standard NIPT panel, which screens for trisomy 21, 18, and 13, does not cover small chromosomal duplications or deletions such as 17p12. Some testing plans offer an optional expanded panel that also covers microdeletions and microduplications, but the specific conditions covered vary by testing facility and plan.
To find out whether a plan you are considering covers the 17p12 region, please contact the testing facility directly. Our article on how NIPT detects microdeletion syndromes and our overview of microdeletion and microduplication conditions may also be helpful (Japanese-language resources).
It is also important to remember that NIPT is a non-definitive screening test. If it returns a positive finding, a definitive diagnosis is made using amniocentesis. From the collected sample, the copy number of the PMP22 gene is examined using methods such as MLPA or chromosomal microarray analysis (CMA). Note that conventional microscopic chromosome analysis (G-banding karyotyping) alone cannot detect a change of this size.
While researching this condition, we searched X (formerly Twitter) for firsthand accounts from people in Japan, but found no recent posts. Given how rare this condition is, a lack of first-person accounts is not unusual. Instead, this article relies on information from public and academic sources, including MGenReviews and GeneReviews Japan.
9. A Message to Families
Seeing the name “Charcot-Marie-Tooth disease type 1A” can be unsettling, and some readers may worry it signals a severe illness. In practice, though, progression is slow, and many people continue working and raising children while using orthotics and rehabilitation as needed.
Ongoing clinic visits and managing orthotic devices over the long term can place a real burden on families. Working together with your medical team and support organizations can help you build a sustainable routine that does not push anyone too hard.
In genetic counseling sessions, we frequently hear the question, “will this be passed on to our next child as well?” In most cases, an accurate test result combined with a review of the family history makes the outlook much clearer. Please don’t try to work through this alone — reach out to a specialist.
Phone consultations are also welcome. Please feel free to contact us at 0120-169-629 (within Japan).
Frequently Asked Questions
Are 17p12 duplication syndrome and Charcot-Marie-Tooth disease type 1A (CMT1A) the same condition?
Yes, the two names refer to the same condition. A single extra copy of the PMP22 gene in the 17p12 region causes Charcot-Marie-Tooth disease type 1A (CMT1A).
What is the difference between 17p12 duplication and deletion?
Both involve the same PMP22 gene and the same 17p12 region, but they are different conditions. Duplication causes CMT1A, while deletion causes hereditary neuropathy with liability to pressure palsies (HNPP); the two also follow a different clinical course.
Is this different from Potocki-Lupski syndrome?
Yes, they are different conditions. Potocki-Lupski syndrome is caused by duplication of the 17p11.2 region and mainly involves developmental delay and intellectual disability. It involves a different set of genes than the 17p12 region responsible for CMT1A.
What symptoms does CMT1A cause?
CMT1A mainly causes gradually progressive muscle weakness and wasting that begins at the extremities, such as the toes. It can also involve foot drop, pes cavus, and sensory disturbance. Progression is usually slow, typically unfolding over several years.
Is it passed on to children?
Because it follows an autosomal dominant inheritance pattern, if a parent carries the duplication, there is roughly a 50% chance of passing it on to each child regardless of sex. It can also arise as a new, spontaneous mutation with no other affected family members. For details specific to your situation, please consult a genetic counselor.
Can prenatal NIPT detect this condition?
It is not covered by the standard panel that screens for trisomy 21, 18, and 13. Some plans offer an optional panel that covers microdeletions and microduplications, but coverage varies by facility, so please check directly with the testing facility you are considering. If a positive finding occurs, a definitive test such as amniocentesis is required.
Medical supervision: Dr. Hiroshi Oka — Director-General, Hiro Clinic (a network of medical corporations) and Lab Director. Graduate of Keio University School of Medicine. Licensed to practice medicine in both Japan and the United States, and holds a medical doctorate (Ph.D.). One of only a small number of certified Lab Directors in Japan. Author of a Japanese-language book on what to know as soon as you learn you are pregnant. This article was prepared with reference to information from public authorities and medical societies, in accordance with medical advertising guidelines. Reported figures can vary across the medical literature; please consult your physician for final decisions on diagnosis and treatment.
References (Japanese-language sources): Charcot-Marie-Tooth disease | MGenReviews (Japan Institute for Health Security) / Charcot-Marie-Tooth disease (Designated Intractable Disease 10) | Japan Intractable Diseases 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
この記事は、 ヒロクリニックNIPTの編集・監修体制 にもとづき、資格を持つ医師が内容を確認しています。
