BACKGROUND– Peripheral neuropathy may result from diverse genetic causes. In recent years molecular diagnostic methods have clarified the relationships between many of these different causes and their resultant clinical phenotypes.REVIEW SUMMARY– Charcot-Marie-Tooth neuropathy type 1 (CMT 1) (demyelinating CMT) is most commonly associated with a duplication on chromosome 17 (CMT 1 A) and, less frequently, with point mutations within the myelin gene PMP22 (on chromosome 17) or in the myelin protein zero (Po) (on chromosome 1; CMT 1B). Hereditary neuropathy with liability to pressure palsies results from a deletion on chromosome 17p, which is reciprocal to the duplication seen in CMT 1A patients. Dejerine-Sottas disease is a less common, severe, demyelinating neuropathy that has been associated with mutations in either PMP22 or Po. X-linked CMT is associated with mutations in the connexin 32 gene. No candidate genes have been identified in CMT 2, but at least three different forms have been identified by genetic linkage analysis. These forms map to chromosomes 1p, 3, and 7. Refsum's disease, resulting from abnormalities of phytanic acid metabolism, is an autosomal recessive cause of demyelinating neuropathy. Familial amyloid neuropathy (FAP) is a less frequently diagnosed cause of hereditary neuropathy. In many cases, FAP arises from mutations in the transthyretin protein and may be treatable with liver transplantation. Mitochondria) DNA mutations may also lead to peripheral neuropathy, but usually in the context of more generalized mitochondrial illness.CONCLUSIONS– Understanding of the molecular genetics of neuropathies has facilitated patient care by providing direct methods for confirming the diagnosis. This should eventually lead to improved therapy for each particular disorder.