Pipis et al. describe the characteristics and longitudinal follow-up of 225 patients with Charcot-Marie-Tooth disease type 2A, caused by mutations in MFN2. They describe how different mutations affect disease onset and rate of progression and identify sensitive clinical assessments that can be used for disease monitoring. The gene discussed is MFN2; the disease is Charcot-Marie-Tooth disease type 2A1.