Hereditary Neuropathy With Liability to Pressure Palsies (HNPP)

What happens in HNPP

Nerves outside the brain and spinal cord are wrapped in myelin, an insulating layer that lets signals travel quickly. The PMP22 gene makes a protein needed for stable myelin. People with HNPP have only one working copy of PMP22 instead of two.

As a result, myelin in places becomes unstable and forms sausage-shaped thickenings, called tomacula (Latin for sausages). When the nerve is compressed or stretched, conduction fails more easily than usual and recovers more slowly. A position that would give anyone brief pins and needles can, in HNPP, cause weakness lasting weeks.

How it is inherited

HNPP is autosomal dominant. Each child of an affected parent has a 1 in 2 chance of inheriting it. Some cases arise from a new deletion with no family history. Symptoms vary a lot, even within families, and some carriers never notice any.

HNPP is the mirror image of the most common form of Charcot-Marie-Tooth disease, CMT1A, in which the same gene is duplicated rather than deleted.

Symptoms

Episodes usually start in the teens or twenties, though they can begin in childhood or later life. Each episode affects a nerve at a point where it is close to the surface or crosses a bone.

Episodes are usually painless, which helps distinguish them from many other nerve problems. Weakness typically starts on waking or after the activity and improves over days to months. Some people develop a mild, lasting peripheral neuropathy with numb feet, reduced reflexes or high arches over time.

How HNPP is diagnosed

1. History: repeated pressure-related palsies, especially at different sites, and similar episodes in relatives.
2. Nerve conduction studies: show slowing at common compression sites in many nerves, including nerves that have never caused symptoms. This widespread pattern strongly suggests HNPP.
3. Genetic testing: confirms the diagnosis by finding the PMP22 deletion in about 80% of people. Rarely, a point mutation in PMP22 is found instead.
4. Nerve biopsy: showing tomacula. Now rarely needed because genetic testing is available.

HNPP is underdiagnosed. Many people are treated for "isolated" carpal tunnel syndrome or peroneal palsy before the pattern is recognized.

Treatment and prevention

There is no medicine that corrects the gene change. Management focuses on protecting nerves and supporting recovery.

Preventing episodes

• Avoid crossing your legs, prolonged kneeling or squatting.
• Do not lean on your elbows; use padded armrests.
• Change position often on long journeys and at a desk.
• Avoid sleeping on your arms or with arms overhead; padded elbow splints at night can help.
• Use a lighter bag over both shoulders rather than a heavy one on one shoulder.
• Be careful with rapid weight loss, which reduces the fat that cushions nerves at the knee.
• Tell your surgeon and anesthetist you have HNPP so pressure points are padded and limbs positioned carefully during operations.
• Avoid medicines known to damage nerves, such as vincristine, where alternatives exist.

During an episode

• Ankle-foot orthosis (brace) for foot drop to prevent tripping.
• Wrist splint for wrist drop or carpal tunnel symptoms.
• Physical and occupational therapy to maintain strength and range of movement.
• Avoid further pressure on the affected nerve.

Surgery

Surgical release of a nerve, such as for carpal tunnel syndrome, is generally approached cautiously in HNPP. It may help when there is clear, persistent compression, but results can be less predictable than usual. Discuss carefully with a specialist familiar with HNPP.

Outlook

HNPP does not shorten life. Most episodes recover fully or nearly so, although recovery may be slower and less complete as people get older or after repeated episodes at the same site. Learning which positions trigger episodes is the single most effective tool.

Frequently asked questions

What triggers HNPP episodes?

Pressure or stretch on a nerve. Common triggers are sitting cross-legged, kneeling, leaning on elbows, sleeping on an arm, carrying a heavy shoulder bag, repetitive wrist movements, and positioning during surgery. Rapid weight loss can make nerves at the knee more vulnerable.

Is HNPP the same as Charcot-Marie-Tooth disease?

They are related but different. Both involve the PMP22 gene. In HNPP one copy is deleted, causing episodes of pressure palsy. In CMT1A the gene is duplicated, causing a slowly progressive neuropathy with weak lower legs and high arches. HNPP is sometimes grouped with the CMT family.

How long does an HNPP episode last?

Most episodes improve within days to weeks, and many resolve completely within 3 months. Some take longer, and a minority leave mild lasting weakness or numbness, especially after repeated episodes at the same nerve.

Is HNPP painful?

The palsies themselves are usually painless, which is one of the distinguishing features. Some people do develop nerve pain, aching or cramps, and a small number have more ongoing discomfort. Pain management follows the same principles as for other neuropathies.

Can I exercise with HNPP?

Yes. Regular exercise is encouraged. Choose activities that do not put sustained pressure on nerves, such as swimming and walking, and avoid long periods of kneeling, heavy weights held in one position, or cycling positions that press on the hands for long periods. Take regular breaks to change position.