Hereditary neuropathy with liability to pressure palsies

The ability to map the loci for inherited neurologic diseases and test positional and functional candidate genes has led to the identification of the molecular basis of many disorders. In particular, with the discovery of important components of peripheral nervous system myelin, rapid progress has been made in a heterogeneous group of demyelinating polyneuropathies well known as the Charcot-Marie-Tooth type 1 syndromes (CMT1; also known as hereditary motor and sensory neuropathy type 1).^1,2 Given the high frequency with which CMT1 patients are encountered in practice, the clinical, electrophysiologic, and histologic features of CMT1 are well known to neurologists.³ Hereditary neuropathy with liability to pressure palsies (HNPP) is a less frequently diagnosed demyelinating neuropathy often classified with the CMT1 syndromes because of its genetic and functional relation to CMT1.⁴ In this issue of Neurology, Sahenk et al. describe an HNPP patient having a point mutation in a myelin gene, and using a mouse xenograft model explore how this mutation produces disease.⁵

HNPP is an autosomal dominant disorder that typically leads to episodic, recurrent motor and sensory peripheral neuropathies.⁴ HNPP may present as an entrapment or compressive neuropathy, typically affecting the peroneal, median, or ulnar nerves at vulnerable sites. HNPP usually begins in …