[Edited by Dr. Phillip Chance]
Hereditary neuropathy with liability to pressure palsies or HNPP is associated with a deletion on chromosome 17p11.2-12. This is the same chromosomal site where CMT1A has been found to have a duplication, and it contains an important myelin gene, peripheral myelin protein-22 gene (PMP22). Therefore, while CMT1A results from having an extra copy of PMP22, HNPP results from the loss of a copy of PMP22.
HNPP is caused by an autosomal dominant gene. HNPP is also a demyelinating form of neuropathy like CMT1A. However, the affected nerves in HNPP are described as having focal regions with “tomaculous” changes or sausage shaped figures, due to the irregular thickening of the myelin sheath.
HNPP causes episodes or periods of numbness and weakness, similar to an arm or leg going to sleep. But, instead of lasting only a few seconds, as it does in a normal person, this numbness and weakness can last from several minutes to months. These episodes may be associated with fairly mild trauma (stretching or pressure on the nerves) which would not ordinarily affect a normal person, such as: leaning on elbows, crossing legs, cutting with scissors, knitting, kneeling, sleeping in the wrong position, etc. It has usually been described as a painless disorder, although some people do have pain, which is probably a subjective sense of numbness. Most individuals with HNPP have normal strength and sensation, unless experiencing an attack.
Typically, persons who have inherited HNPP will develop symptoms in their teens or twenties, but individuals may be first symptomatic during childhood or late adulthood. Like CMT, there is a wide range in how severely people are affected. Many are so mild that they are unaware that they have a problem. Others develop the symptoms of a more generalized hereditary motor and sensory neuropathy, which on occasion may be misdiagnosed as a form of CMT. Carpal tunnel syndrome is frequently seen in patients with HNPP.
As a hereditary neuropathy it is progressive, though to what extent it will progress in any individual is unknown. There is no treatment or cure for HNPP. People are usually advised to avoid activities which they have learned cause symptoms to develop. Leg crossing and leaning on elbows is discouraged. AFOs can be used during periods of acute peroneal nerve palsy or for permanent foot drop and/or balance problems.