We report MRI findings in a family with an autosomal-dominant, adult-onset neurological disorder. The clinical picture, the white matter changes detected on MRI and the absence of any laboratory abnormality suggested the diagnosis of leukodystrophy with an unknown biochemical defect. Autosomal-dominant inheritance is extremely rare in this kind of disease, and most reported families have not undergone MRI. We performed MRI and clinical examination of 17 members of our family; 9 affected subjects, at different stages of the disease, were detected. The most characteristic MRI findings were initially symmetrical areas of signal change in the white matter of the trigonal region; demyelination extending thereafter to the frontal and parietal regions, partially involving subcortical white matter; the temporal lobe and optic radiations were less involved; the internal capsule and corpus callosum were involved later, in a dorsoventral direction; patchy demyelination was evident in the late stages in the brain stem; the cerebellum was spared even in the latest stages of the disease. While pathological examination is essential to characterise and classify these kinds of diseases, MRI can make substantial contributions to understanding their natural history, and to detect early signs of the disease.