Patients with diastrophic dysplasia have walking difficulties of obscure etiology; some are even wheelchair-bound. To explore the problem, physical examination, treadmill, magnetic resonance imaging (MRI), and electroneurophysiologic studies were performed on 87 patients (56 females, 31 males) with an average age of 31 (range 3-56) years. Mobility of the spine, hips, knees, and feet was diminished. Some of the patients were obese (mean body mass index 27.0 kg/m(2)). In the treadmill study, patients were able to walk an average of 638 m (range 0-1,618 m). On MRI, five patients showed compression of neural structures; one of them also had clinical symptoms. Somatosensory evoked potentials and electroneuromyography revealed evidence of compression of neural structure in three (3%) and two (3%) patients, respectively. The walking difficulties seem to have a multifactorial etiology: flexion contractures of the knees, early and rapid osteoarthrosis, equinus or equinovarus foot deformities, and obesity, but only rarely spinal stenosis.