What would the brain look like in Angelman syndrome?

Scientific knowledge relies on sound evidence. In many domains the latter is still erratic, so that the former is provisionally replaced by inference based on scant data provided unsatisfactorily answered questions remain critically open for scrutiny. Neuroimaging and pathology of Angelman syndrome provide an illustration of this process. Although this condition is primarily characterised by various aspects of brain dysfunction and despite the relatively good availability of neuroimaging techniques in centres where the syndrome has been extensively studied for several dozens of years, there have been surprisingly few neuroimaging studies. Harry Angelman described the skull X-ray and pneumoencephalogram of his three patients when he first characterised the syndrome in 1965. Skull X-rays were normal, excluding craniosynostosis as a cause for the patients’ microcephaly; air encephalograms showed slight ventricular dilatation in all children and increased presence of air around the cortex, suggesting mild cortical–subcortical atrophy. These techniques have become obsolete with the advent of computed tomography and of course magnetic resonance imaging (MRI). In their aetiolological work-up for developmental delay or epilepsy, many patients undergo MRI before the diagnosis of Angelman syndrome is established, allowing for at least retrospective studies but even those have been extremely limited. The general, largely uncontrolled experience with structural imaging techniques has been a lack of abnormalities except for eventual, mild to moderate non-specific cerebral atrophy and more rarely cerebellar atrophy. In this issue of the European Journal of Paediatric Neurology, Harting and her colleagues present a retrospective MRI study involving nine children with Angelman syndrome, i.e. the largest group studied to date in this way although several hundreds of patients have been reported and many more diagnosed over more than 40 years. Interestingly, they report white matter changes in most of these patients and