My Not-So-Secret Diary

Understanding HNPP: Hereditary Neuropathy with Liability to Pressure Palsies

*The following information was extracted from the CMT Research Foundation website at cmtrf.org.

Charcot-Marie-Tooth disease encompasses many different subtypes grouped into many different classifications. Most subtypes have “CMT” in their name, but some do not, such as Hereditary Neuropathy with Liability to Pressure Palsies—a CMT subtype classified with CMT1.

HNPP is caused by various mutations in the PMP22 gene. This gene is responsible for instructing Schwann cells to make peripheral nerve myelin. The peripheral nerves are all the nerves that lie outside of the brain and spinal cord—except for the optic nerves—and connect the brain and spinal cord to the rest of the body. These nerves control muscle movement and touch sensations signals (temperature, pain, etc.).

The peripheral nerves are a lot like electrical wire, with two basic components: a metal wire inside and a protective sheath on the outside. The part of the peripheral nerve that transmits a signal (the metal) is the axon. The outer sheath that protects the axon is peripheral nerve myelin. The gene mutations that cause HNPP cause this peripheral nerve myelin to malfunction.

We normally have two copies of the PMP22 gene. The common cause of HNPP is a deletion of one copy of this gene. Having only one copy of this gene causes Schwann cells to malform peripheral nerve myelin. Over time, as HNPP progresses, the peripheral nerves start to lose their protective myelin sheath. (Additionally, rare cases of HNPP are caused by a mutation within the PMP22 gene, referred to as a “point mutation” rather than by a deletion of one copy of this gene.)

Symptoms of HNPP

The symptoms of HNPP aren’t too different from the common symptoms of CMT in general. CMT patients who have HNPP also experience both muscle weakness and sensory loss. HNPP is generally not clinically distinguishable from other CMT subtypes.

HNPP symptom onset can start at any time, but usually show up by the time the patient is 30 years old. Symptoms such as numbness, tingling, and muscle weakness are common, just as in CMT in general. However, HNPP symptoms can be episodic and localized to a certain area of the body – the only CMT subtype with this episodic nature.

Areas of the Body Affected

In HNPP, the most affected areas of the body are the legs, feet, elbows, wrists, or hands. Leaning against hard objects/sharp corners, wearing tight gloves, wearing tight socks, etc., can exacerbate symptoms/trigger an episode. Patients who have HNPP have to be careful to not wear clothes or shoes that are too tight. If using AFOs, the orthotist must be careful to not create pressure points. Due to the type of abnormality present in the peripheral nerve myelin with HNPP, the peripheral nerves are sensitive to pressure/compression and can be easily injured resulting in a pressure palsy. A pressure palsy can lead to numbness, weakness, muscle atrophy, and even paralysis of the muscle controlled by the affected peripheral nerve. Sleeping on a mattress that is too firm can create a pressure point in the shoulder, elbow, hip, etc., too, leading to a triggered episode. Stretching improperly can also trigger an episode.

Length of Episodes

HNPP episodes sometimes resolve in hours but can also last for days, weeks, or months. Sometimes, the palsy can become permanent. Symptom severity varies with each episode depending on which nerve(s) are affected—a motor nerve or a sensory nerve, or both. Typically, symptoms fully resolve in time as the nerve heals from the pressure/compression injury. Usually, when the pressure/compression injury becomes permanent in HNPP, the symptoms tend to be mild, but they can sometimes be severe and debilitating. True to CMT, there’s no reasonable way to predict the severity nor duration of an episode.

How HNPP Has Affected Me

Early Years

My symptoms of HNPP started way back in high school. I would notice that my arm would go completely numb while I was asleep if I had been lying on it. When I would wake up and roll over, my arm would fall and hit me in the face. I had absolutely no control over my arm. The numbness would last for less than a minute. Feeling and function would soon return after an intense few seconds of tingling. It always scared me when it happened because I could not move my arm at all.

Pressure Palsies

A major part of HNPP has to do with the pressure palsies. Each person can experience these in different ways. The severity and longevity of the palsy can vary from person to person and from episode to episode. As I’m sitting on a hard chair typing this, my legs are tingling, and this is an example of one of my minor palsies. Once I get up and move around, my legs will stop feeling this way. But as long as I am sitting, it will continue.

Another example of this comes from when I was in weightlifting class in high school. I did a couple of 90lb deadlifts and shortly after, I could not raise my left arm above my head. My scapula (shoulder blade) would wing out very noticeably. This continued for days and weeks, so I went to the doctor and then to a specialist. They had never seen anything like this before. At that time, I did not know that I had HNPP so it could not be a part of figuring out what was wrong. I ended up doing some physical therapy but still had the issue. It was a problem for years, then eventually went away after I had gotten used to living that way.

Later Years

As a young adult I noticed some random symptoms here and there but not enough to think that something was wrong with me. Once, I had tingling and numbness on my chin which was really weird. I still get chin numbness every once in a while. Also, my hands would get tingly and numb while working on the computer. I just figured it was from the repetitive typing movements. My doctor prescribed me some splints to wear while typing so my wrists would stay in the correct position. This only helped a little bit.

Carpal Tunnel Syndrome

Years went by and I was diagnosed with carpal tunnel syndrome and was scheduled for surgery. The specialist that I saw did some testing including an EMG and Nerve Conduction Study. Both were abnormal so I was told that my problem may be systemic. If so, the carpal tunnel release surgery may not have a lasting effect on me.

I chose to have the surgery on both wrists. Improvement was noticed for a short time, then symptoms slowly returned. After a couple of years, the numbness and tingling were back, and I noticed more weakness in both hands. My grip strength had diminished, and I started dropping things more often. Especially things that were lightweight.

When I Decided to See a Doctor

When my fourth child was an infant, I went for a little hike. Nothing strenuous. I went to step up onto a rock, and I noticed that my leg couldn’t support my weight. It should have been a simple step up like with any other step, but I could not do it.

My muscles felt so weak and unable to perform such an easy task. It immediately got my attention, and I was concerned because this wasn’t normal for me, up to this point. Following that experience, I tried to exercise like I did prior to having baby number four. Something felt off. It felt different. My legs felt like they didn’t want to work. Kind of like a Jello feeling. I tried to run like I had done for years, but I could not go very far before I had to stop. It was so frustrating and concerning.

At this point, I decided to see my doctor to get a referral to a neurologist. My arms and legs were weak, and I experienced numbness and tingling more often. It was time.

First Neurologist

I went to a neurologist for the first time, and he did a complete workup. He did not do an EMG or Nerve Conduction Study though. Instead, the results from my previous testing were sent over for him to review. He then sent me to get a brain MRI. I had several follow up appointments and then at my final appointment, he gave me a diagnosis of Fibromyalgia. That diagnosis hadn’t even crossed my mind as a possibility. I really thought that I had MS because of the muscle weakness that I was experiencing. After sharing my thoughts with him he said, “Well, you should be glad it’s not neurological.” This guy totally dismissed my concerns and made me feel like an idiot. He didn’t take me seriously at all during any of the visits.

I left his office feeling down because I felt like there was more going on with my body than Fibromyalgia. Not that Fibromyalgia isn’t awful. Just that it didn’t fit with my complaints of numbness, tingling, and muscle weakness. I was still pretty scared that there was something worse going on.

Second Opinion

My symptoms continued on for a while, and then I decided to go back to my primary care doctor. I wanted to get a referral for a second opinion with a different neurologist. My doctor obliged and I soon had my appointment. When the doctor came in and asked what I was being seen for, I was up front with him about my experience with the last neurologist. I made it clear that I was there for a second opinion and really wanted to see someone who was going to take my concerns seriously. After hearing my list of symptoms and considering my age, he agreed that something else was likely going on.

Additional Testing

This doctor was very thorough. He performed a full neurological examination which is divided into five parts: mental status, cranial nerves, motor function, sensory function, and reflexes.

Mental Status

The mental status exam checks the level of alertness, mood, orientation, and cognition. Things like stating your name, where you are, date and time, etc. I was asked to follow commands like “Touch your right ear with your left index finger.

Cranial Nerves

The cranial nerves exam tests the special senses like vision, hearing, smell and taste. My pupil reactivity was assessed by shining a light in my eyes. Peripheral vision, visual acuity, and eye movements were also tested. Other parts of the cranial nerve test included being asked to stick out my tongue, turn my head from side to side, and shrug my shoulders.

Motor Function

The motor function exam tests muscle strength. This was a good test for me because of the weakness that I was experiencing. Both upper and lower extremities were tested. An example of one of the tests is the drift test. You stand up with eyes closed and arms outstretched in front you with palms facing upward. Count to ten out loud without moving your arms and this can detect any weaknesses on either side of the body. Other parts of the exam use resistance provided by the examiner. For example, the examiner will try to bend your arm while you try to keep it straight. My grip strength was tested by squeezing the examiners thumbs as hard as I could. I did not have much grip strength.

Sensory Function

Sensory function tests the sense of touch by having you close your eyes, and the examiner lightly touches your skin with a pin to see if you can tell whether it was the pointy or dull side that touched you. Proprioception, or your body’s position and movement, is tested. With your eyes closed, the examiner will move a toe up or down and the patient has to say which direction it was moved.

Reflexes

Reflexes are tested with a rubber hammer. Responses are checked at the knee, elbow, wrist, and ankle. Sometimes the bottom of the foot or the fingernail of the middle finger are also tested. Since my neurologist suspected a certain diagnosis, he also observed me walking and had me slide the heel of one foot up and down the shin of the opposite leg.

EMG and NCS

Lastly, the doctor performed an EMG (electromyography) and a Nerve Conduction Study. These tests use a bunch of needles that are poked into the skin and electrical impulses are sent through in order to test how well the nerves and muscles respond. In my case, my body responded like that of an 85 year old. I was in my mid-thirties at the time.

The Final Diagnosis

Given the results to all of the tests that were performed on me, my neurologist suggested genetic testing. He told me that he suspected that I had HNPP (Hereditary Neuropathy with Liability to Pressure Palsies). The only way to know for sure is through genetic testing.

I agreed to have the testing done and I finally got my answer. My symptoms are (and were) do to HNPP. I have a deletion of the PMP22 gene. There is no cure for this disease but thankfully it is not life threatening.

At the end of the visit where we discussed my diagnosis, I thanked the doctor for listening to me and for taking my concerns seriously. Even though the diagnosis was unfortunate, I was glad to finally have an answer.