Objective:To extend the phenotypic description of Charcot-Marie-Tooth disease (CMTX1) and to draw new genotype-phenotype relationships.Methods:Mutations in GJB1 cause the main X-linked form of CMTX (CMTX1). We report cross-sectional data from 160 patients (from 120 different families, with 89 different mutations) seen at the Inherited Neuropathies Consortium centers.Results:We evaluated 87 males who had a mean age of 41 years (range 10–78 years) and 73 females who had a mean age of 46 years (range 15–84 years). Sensory-motor polyneuropathy affects both sexes, more severely in males than in females, and there was a strong correlation between age and disease burden in males but not in females. Compared with females, males had more severe reduction in motor and sensory neurophysiology parameters. In contrast to females, the radial nerve sensory response in older males tended to be more severely affected compared with younger males. Median and ulnar nerve motor amplitudes were also more severely affected in older males, whereas ulnar nerve motor potentials tended to be more affected in older females. Conversely, there were no statistical differences between the sexes in other features of the disease, such as problems with balance and hand dexterity.Conclusions:In the absence of a phenotypic correlation with specific GJB1 mutations, sex-specific distinctions and clinically relevant attributes need to be incorporated into the measurements for clinical trials in people with CMTX1.ClinicalTrials.gov identifier:NCT01193075.

[structure: see text] A chiral aldehyde that forms resonance-assisted hydrogen bonded imines with amino acids has been developed. This hydrogen bond not only increases the equilibrium constant for imine formation but also provides a highly downfield-shifted NMR singlet for evaluating enantiomeric excess and absolute stereochemistry of amino acids.

This study provides insight into the assessment of CTS symptom severity and patient-reported outcomes to CTS therapy in individuals with inherited neuropathies. The SSS appears useful for evaluation of CTS symptoms and patient-reported outcomes following CTS interventions in individuals with inherited neuropathies. Muscle Nerve 57: 388-394, 2018.