Hereditary Neuropathy with Pressure Palsies (HNPP) is a genetic disorder affecting the peripheral nervous system. HNPP is characterized by recurrent episodes of temporary numbness, tingling, and muscle weakness, often in the limbs. These recurrent symptoms arise because the peripheral nerves are unusually susceptible to physical pressure and minor trauma that would not typically bother an unaffected person. While HNPP is a chronic condition, the severity of symptoms varies widely, ranging from nearly asymptomatic cases to those who experience prolonged episodes.
The Genetic Basis of HNPP
HNPP is typically inherited in an autosomal dominant pattern, meaning a child needs to inherit only one copy of the faulty gene from one parent. The molecular cause is usually the deletion of a segment on chromosome 17 containing the Peripheral Myelin Protein 22 (PMP22) gene. This deletion accounts for about 80% of cases, though other PMP22 mutations can also be responsible.
The PMP22 gene provides instructions for making the Peripheral Myelin Protein 22, a component of the myelin sheath. The myelin sheath is a protective coating that insulates nerve fibers and ensures the quick transmission of electrical signals. Because individuals with HNPP are missing one functional copy of the gene, they produce only about half the normal amount of the PMP22 protein.
This reduced protein level leads to haploinsufficiency, resulting in structurally compromised myelin. The peripheral nerves develop abnormal, focal thickenings on the myelin sheath called tomacula, making them highly vulnerable to mechanical stress. This faulty myelin structure causes the nerves to be easily damaged by slight, sustained pressure, leading to the characteristic episodic symptoms.
Distinctive Symptoms: The Pressure Palsies
The hallmark of HNPP is the occurrence of focal neuropathies, or “pressure palsies,” which are episodes of sensory and motor deficits confined to the distribution of a single nerve. These episodes are often triggered by mild activities involving sustained compression or repetitive movements. Common triggers include crossing the legs for an extended period, leaning on an elbow, wearing a tight wristband, or carrying heavy bags.
The manifestations depend on the specific nerve affected, but they typically involve temporary numbness, tingling, or muscle weakness. For instance, compression of the peroneal nerve at the knee can cause “foot drop,” making it difficult to lift the front of the foot. Involvement of the ulnar nerve at the elbow or the median nerve at the wrist can lead to hand weakness, finger numbness, or symptoms resembling carpal tunnel syndrome.
These episodes can last from minutes to several months and are usually non-painful. While recovery is often complete, about half of all episodes result in incomplete recovery. Repeated incidents can cause mild, permanent sensory loss or muscle weakness in the affected area. Some individuals may also experience generalized symptoms, such as chronic pain, fatigue, or a mild, symmetric sensory-motor polyneuropathy later in life.
Methods of Diagnosis
Confirming an HNPP diagnosis begins with a thorough review of the patient’s clinical history, looking for recurrent focal neuropathies and a family history of similar symptoms. Because the symptoms can be temporary and variable, HNPP is sometimes misdiagnosed as other neurological conditions. A high degree of clinical suspicion is necessary to correctly identify the disorder.
Medical professionals use Nerve Conduction Studies (NCS) to objectively assess nerve function by measuring how quickly electrical signals travel through the nerves. In individuals with HNPP, NCS typically shows evidence of demyelination, indicating slowed nerve conduction velocity. This slowing is particularly noticeable at sites where nerves are commonly compressed, such as the elbow or wrist.
Genetic testing provides definitive confirmation of HNPP. This test analyzes the DNA to specifically identify the deletion of the PMP22 gene on chromosome 17. While the deletion accounts for the majority of cases, genetic testing can also detect point mutations or small deletions within the PMP22 gene that result in the condition.
Managing Life with HNPP
Management focuses on preventive strategies and supportive care to minimize nerve trauma and alleviate symptoms. The primary goal is educating the patient on avoiding activities that could trigger a pressure palsy. This includes lifestyle modifications, such as being mindful of posture, avoiding prolonged sitting with crossed legs, and refraining from leaning on elbows for long periods.
Protective padding or supports can help shield vulnerable nerves from mechanical stress. For example, wrist splints or elbow pads can be used during activities where compression is likely. Physical and occupational therapy are valuable tools, helping to strengthen muscles and maintain mobility, especially following an acute palsy episode.
In clinical settings, such as during surgery, extreme caution is necessary to ensure proper patient positioning and prevent nerve compression. Maintaining a healthy body weight is also recommended, as excess weight can increase pressure on peripheral nerves. While most episodes resolve completely, individuals experiencing protracted or incomplete recovery may sometimes benefit from corticosteroid therapy.