A novel type of hereditary motor and sensory neuropathy characterized by amild phenotype

Background: Three loci for autosomal dominant hereditary motor and sensory neuropathy type I (HMSN I) or Charcot-Marie-Tooth disease type 1 (CMT1) hav e been identified on chromosomes 17p11.2(CMTIA), lq21-q23 (CMTIB),and 10q21 .1-q22.1 (designated here as CMTID). The genes involved are peripheral myel in protein 22 (PMP22), myelin protein zero (MPZ), and the early growth resp onse element 2 (EGR2), respectively. Probably a fourth locus (CMTIC) exists since some autosomal dominant HMSN I families have been excluded for linka ge with the CMTIA and CMTIB loci. Four loci for autosomal dominant heredita ry motor and sensory neuropathy type II (HMSN II) or Charcot-Marie-Tooth di sease type 2 (CMT2) have been localized on chromosomes lp35-p36 (CMT2A), 3q 13-q22 (CMT2B), 7p14 (CMT2D), and 3p (HMSN-P). Objective: To describe the clinical, electrophysiologic, and neuropathologi cal features of a novel type of Charcot-Marie-Tooth disease. Patients and Methods: We performed linkage studies with anonymous DNA marke rs flanking the known CMT1 and CMT2 loci. Patients and their relatives unde rwent clinical neurologic examination and electrophysiologic testing. In th e proband, a sural nerve biopsy specimen was examined. Results: Linkage studies excluded all known CMT1 and CMT2 loci. The clinica l phenotype is mild and almost all affected individuals remain asymptomatic . Electrophysiologic and histopathological studies showed signs of a demyel inating neuropathy, but the phenotype is unusual for either autosomal domin ant HMSN I or HMSN II. Conclusion: Our findings indicate that the HMSN in this family represents a novel clinical and genetic entity.