Statistics from Altmetric.com
Are we on the verge of molecular Armageddon, to be ravaged by the onslaught of giant, genetically modified, giant tomatoes? Are we entering a molecular Utopia, where all the world's ills will be solved with a golden key to a nucleotide code or at the gateway of a eugenic nightmare? As far as epilepsy is concerned, a central message of this book is that clinical heterogeneity is the rule—the genes are only part of the story. Those of us with a deep suspicion (acquired not innate) of genetic models of life the universe and everything, can breathe a sigh of relief.
There are substantial methodological problems in genetic studies of epilepsy. It is a paroxysmal disorder, with age dependent expression, no diagnostic test, and frequent misdiagnosis. A tribute to workers in the field is that progress has been made despite these difficulties. Several early chapters consider benign childhood epilepsy with centrotemporal spikes. The characteristic EEG disturbance of this condition is probably inherited in autosomal dominant fashion, but only about 10% of siblings have epilepsy and they may have many different clinical varieties of epilepsy. Indeed there seems to be an association between this benign partial epilepsy and idiopathic generalised epilepsy, blurring the classic divisions of epilepsy classification.
Autosomal dominant nocturnal frontal lobe epilepsy is genetically and clinically relatively well defined and is sometimes due to mutations of the nicotinic acetyl choline receptor. Even here the clinical expression of the same mutation may vary from a self limiting period of seizures to refractory nocturnal epilepsy with dozens of seizures each night. Other genetic epilepsy syndromes have been described recently; familial temporal lobe epilepsy and epilepsy with variable foci.
MRI has allowed the in vivo classification of subtle cortical dysplasias as well as more gross disorders such as tuberose sclerosis, whose genetic bases are becoming clear. Subcortical band heterotopia or periventricular nodular heterotopia, are seen only in females and have been shown to be X linked and fatal in males.
How do genetic abnormalities produce epilepsy and what is the cause of the clinical heterogeneity? Here there are only questions. Abnormalities of regulatory homeobox genes may reproduce some aspects of cortical dysplasia and have been identified in humans too. The nicotinic acetylcholine receptor may be involved in development, cortical excitation, or the regulation of the thalamocortical sleep wake cycle—but all is speculation at this stage. Animal models may demonstrate changes in anatomy and chemistry and transgenic animal models may be valuable in exploring pathophysiology. Genetics is providing a gateway to pathophysiology but the clinical heterogeneity even in the most genetically uniform disorders suggests that these processes will not easily be revealed by simply understanding the genes. The relevance of the rarer genetic syndromes to commoner forms of epilepsy remains to be established. Targets for novel therapies are still a long way off.
This book provides a clear account of many genetically determined, focal epilepsies, a balanced view of their genetic components, and clinical and scientific methods for their future exploration. It will be of interest primarily to epilepsy specialists and geneticists.
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.