We have previously demonstrated that patients with Charc ot-Marie-Tooth Disease (CMT), the most common inherited peripheral neuropathy, have high risk factors for heart disease, including high body fat percentage, obesity, poor exercise tolerance, and an increased incidence of type 2 diabetes 3.5 times the national average. During exercise, heart rate and metabolic demand normally share a linear relationship with a slope equal to 1.0, which defines the normal chronotropic response (CR). Chronotropic incompetence (CI) is a risk factor for heart disease and results when heart rate fails to increase appropriately with exercise and is denned as a ratio of heart rate reserve/metabolic reserve <0.8. PURPOSE: To determine the relationship between CR and demographic, performance, biometric, and morphometric characteristics in patients with CMT. METHODS: Twenty CMT patients (9 men, 11 women), mean age 45±9y, participated in a 12-week resistance training protocol. Outcomes included: muscle fiber diameter, body composition, aerobic capacity, maximal voluntary isometric strength (MVIS), questionnaire-determined exercise soreness and fatigue, and activities of daily living (ADL) timed motor performance. Eighteen patients (8 men, 10 women) were evaluated for CI at baseline using a bicycle graded exercise test (GXT) and plotting heart-rate reserve for each GXT stage against metabolic reserve to calculate the chronotropic index (CRI). Pearson-product correlations were used to determine if a relationship existed between CRI and demographic data, body composition, muscle fiber size, strength, ADLs, and training-related soreness and fatigue. RESULTS: 39% of patients were found to have CI with a CRI <0.8 during graded exercise. CRI was significantly correlated to post-training Type I fiber cross-sectional area (r=.72, p=.04) and percent of age-predicted VO (r=.54, p=.02), while there was a trend for self-reported training fatigue (r=−.50, p=.08) and soreness (r=−.54, p=.06) to be inversely correlated. Additionally, CMT patients had twice the incidence of CI compared to age and geographically-matched persons at high risk for heart disease without CMT. CONCLUSION: CMT patients at high risk for heart disease have an incidence of CI that is twice the rate of similar high-risk patients without CMT. CRI was positively related to hypertrophy of Type I fibers after resistance training, but not to training volume or any other performance variable. There is a trend toward a negative relationship between CRI and training induced fatigue and soreness.