Figure 1.

The shaded area in the middle and the right of the figure illustrates the clinical manifestations of the proposed aetiological pathways that result in the early and then the later PWS phenotype. The pathway at the top of the figure is specific to those with the mUPD or imprinting centre defect form of PWS and, we hypothesis, this results in the increased risk of psychotic illness with age in this population. The next pathway down illustrates the direct effect of the absence of maternally imprinted gene expression on brain development and specifically the cortex and subcortical structures. The pathway at the bottom of the figure illustrates the hypothesised indirect effect of the PWS genotype, primarily on hypothalamic development, because the absence of SNORD116 results in the down regulation of placental nutritional pathways.

*affective instability and the risk of non-psychotic affective disorder common to all PWS genotypes.

HPA: Hypothalamic Pituitary Axis.