Hereditary Neuropathy with Liability to Pressure Palsies (HNPP) is caused by a deletion of one copy of the PMP22 gene. Most people have two copies of this gene. Individuals with HNPP have only one. This reduced gene dosage affects the stability of peripheral nerve myelin, making nerves unusually susceptible to mechanical stress or compression.
HNPP is autosomal dominant, meaning that just one of the gene’s two copies needs a mutation to cause this subtype.
Despite its name, HNPP is a CMT subtype. Because HNPP is a demyelinating form of CMT and autosomal dominant, it is classified as a CMT1 subtype. Although HNPP is most commonly caused by a missing PMP22 gene copy, it is sometimes caused by a point mutation within the gene.
Clinical Features
HNPP symptoms typically begin in the first or second decade of life. Unlike other CMT subtypes, symptoms are often episodic and are precipitated by mechanical compression, pressure, or repetitive use of a nerve. Episodes may resolve partially or completely, though recurrence is common. Nerve conduction studies show features of a demyelinating neuropathy, often with focal slowing at compression-prone sites.
HNPP symptoms may include:
- Transient, recurrent weakness affecting the feet or lower legs, particularly involving the peroneal nerve
- Episodic weakness affecting the hands or arms, including muscles supplied by the radial, ulnar, or median nerves
- Foot drop or wrist drop following pressure or prolonged positioning
- Reduced sensation in affected nerve distributions
- Reduced reflexes
- Recurrent pressure palsies triggered by minor compression
- Vocal cord paralysis (reported in rare cases)
- Delayed recovery following nerve compression
- Additional symptoms not listed here
Disease Course
HNPP shows wide variability in the severity and frequency of episodes. Some individuals experience infrequent, mild episodes with near-complete recovery, while others develop more persistent weakness or sensory changes over time. Disease progression is generally slow, and life expectancy is not reduced.
