Hereditary recurrent focal neuropathies - Clinical and molecular features

The authors review the molecular genetics and pathophysiology of hereditary recurrent focal neuropathies: hereditary neuropathy with liability to pres sure palsies (HNPP) and hereditary neuralgic amyotrophy (HNA). Significant progress in the understanding of HNPP and HNA has been achieved. HNPP and H NA are distinct clinical and pathologic disease entities with autosomal dom inant inheritance. Molecular genetic studies have shown that HNPP and HNA a re located on chromosome 17 but at distinct genetic loci (17p11.2 for HNPP, 17q25 for HNA). The 1.5 megabase deletion in 17p11.2 is the major cause of HNPP. This interstitial deletion causes the complete loss of one allele of the peripheral myelin protein 22 (PMP22) gene. Interestingly, rare HNPP pa tients are found without the 1.5 megabase deletion. However, these patients have distinct mutations in the PMP22 gene resulting in altered expression of the PMP22 protein. Current molecular genetic tests and clinical guidelin es allow improved diagnosis, prognosis, and genetic counseling for patients with HNPP. Such tests are not available for HNA, because the disease-causi ng gene remains unknown. Molecular genetic advances in HNPP and HNA, as wel l as the study of transgenic animal and cellular models, will provide a mor e precise understanding of the disease mechanisms and will lead to the deve lopment of effective therapeutic tools for patients with inherited and spor adic recurrent peripheral neuropathies.