The term epilepsy encompasses a heterogeneous group of disorders, with a lifetime cumulative incidence of 3%. Genetic factors are thought to contribute to the aetiology in up to 60% of cases. Various molecular and cellular mechanisms give rise to epilepsy, and epilepsy genes fall into several distinct categories. They include genes in which mutations cause abnormal ion-channel function, disordered brain development, progressive neurodegeneration and disturbances of cerebral energy metabolism. In this review, we have focused on current understanding of the molecular genetic bases of human inherited epilepsies. Particular reference has been given to specific idiopathic epilepsies, neuronal migration disorders (cortical dysgeneses) and the progressive myoclonic epilepsies, and how information about this group of disorders might be used to develop new treatment strategies.

We have just emerged from “the Decade of the Brain”, yet in so many ways it was the “Decade of the Genome”. What relevance does the remarkable advance in knowledge in genetics and neuroscience over that period have to our understanding of child psychopathology? When the complexity of the genetic systems involved in behavioural regulation of relatively simple organisms such as the nematode worm Caenorhabditis elegans or the fruitfly Drosophila melanogaster is considered, the possibility of comprehending the links from genes to behaviour in the developing child seems remote. Yet, the principles of investigation in model systems are not so different to those that should apply in humans. This review draws out the parallels, and introduces recent findings from behavioural studies of C. elegans, D. melanogaster, and the laboratory mouse, as well as humans, to illustrate the point.

There are many ways of describing and explaining the properties of living systems; causal, functional, and reductive accounts are necessary but no one account has primacy. The history of biology as a discipline has given excessive authority to reductionism, which collapses higher level accounts, such as social or behavioural ones, into molecular ones. Such reductionism becomes crudely ideological when applied to the human condition, with its claims for genes “for” everything from sexual orientation to compulsive shopping. The current enthusiasm for genetics and ultra-Darwinist accounts, with their selfish-gene metaphors for living processes, misunderstand both the phenomena of development and the interactive role that DNA and the fluid genome play in the cellular orchestra. DNA is not a blueprint, and the four dimensions of life (three of space, one of time) cannot be read off from its one-dimensional strand. Both developmental and evolutionary processes are more than merely instructive or selective; the organism constructs itself, a process known as autopoiesis, through a lifeline trajectory. Because organisms are thermodynamically open systems, living processes are homeodynamic, not homeostatic. The self-organising membrane-bound and energy-utilising metabolic web of the cell must have evolved prior to so-called naked replicators. Evolution is constrained by physics, chemistry, and structure; not all change is powered by natural selection, and not all phenotypes are adaptive. Finally, therefore, living processes are radically indeterminate; like all other living organisms, but to an even greater degree, we make our own future, though in circumstances not of our own choosing.