Brain, Vol. 122, No. 11, 2196-2197,
November 1999
© 1999 Oxford University Press
Book reviews |
GENETICS OF FOCAL EPILEPSIES.
.
UCL Medical School, London, UK
This excellent book should be of very great interest to a wide range of readers, including neuroscientists interested in how basic molecular neurobiology is illuminating a hitherto mysterious group of disorders, and clinical neurologists interested in the latest advances in this fast-moving area of epileptology.
The book is based on a meeting held in Avignon, France, in September 1996, but is far more than the proceedings of a symposium. All the contributors are authorities in their field, and have provided detailed chapters covering their special interests. Most importantly, all the recent advances have been included so, unusually, the book is up-to-date with regard to the current literature.
The subtitle, `Clinical Aspects and Molecular Biology', gives an indication of the range of perspectives. The book is divided into seven parts, each with between three and six separate chapters. Parts I–V deal with the genetics of specific focal epilepsies, including benign childhood epilepsy with centro-temporal spikes, idiopathic focal epilepsies of infancy, autosomal dominant focal epilepsies such as nocturnal frontal lobe epilepsy, and miscellaneous epilepsies such as reading and hot-water epilepsies. Part VI deals with the exciting recent advances in molecular genetics, including the role of ion channels such as the neuronal nicotinic acetylcholine receptor, and the role of homeobox genes in the developing brain. Part VII deals with animal models, both naturally occurring and transgenic.
In Part I, there is a fascinating historical account of the discovery of `benign rolandic epilepsy', followed by an excellent review of the genetics of partial epilepsies by Berkovic and Scheffer. This includes a lucid discussion of the intricacies of genotype–phenotype correlations in the epilepsy field. The challenge, as they comment, is to define clinical entities with biological meaning, no easy task when dealing with paroxysmal dysfunction in what is probably the most complex biological machine in the universe. In Chapter 3, Massimo Pandolfo gives a useful, detailed and scholarly review of the current strategies available for the molecular-genetic dissection of inherited epilepsies.
Part II is devoted to the genetics of benign childhood epilepsy with centro-temporal spikes (rolandic epilepsy) and related conditions. Orvar Eeg-Olofsson from Uppsala, where several of the early studies of this disorder were undertaken, reviews the genetic data which now clearly indicates a multifactorial basis for this phenotype. Choy and co-authors give an account of 21 families studied in Malaysia, and the Kiel group, Neubauer, Stephani and Doose, describe their extensive and pioneering work on this phenotype which has recently led to identification of a locus on 15q44.
Part III deals with idiopathic focal epilepsies of infancy. Guipponi et al. describe their productive investigations which identified a BFIC locus on 19q and the evidence for locus heterogeneity. Watanabe gives an authoritative account of benign partial epilepsies with complex partial seizures and with secondarily generalized seizures, which will be of particular interest to paediatric neurologists.
Part IV is very substantial and gives, in six chapters, an important overview of the recently delineated autosomal dominant focal epilepsies. In Chapter 9, Ingrid Scheffer provides a brief review of autosomal dominant nocturnal frontal lobe epilepsy. It is difficult to overemphasize the scientific importance of this condition in which the first gene for an inherited idiopathic epilepsy was identified. In Chapters 10, 12 and 13, Sam Berkovic and Ingrid Scheffer describe the clinical features of the newly delineated syndromes, familial temporal lobe epilepsy, familial partial epilepsy with variable foci and rolandic epilepsy with speech dyspraxia. In Chapter 11, Ruth Ottman and her group describe the phenotype of autosomal dominant partial epilepsy with auditory features, including the pedigree in which they established linkage on chromosome 10q22–24. Finally, in Chapter 14, a group of European neurologists from France, Italy, Switzerland, Spain and Germany gives an account of a further 21 families with dominant partial epilepsy, bringing the total number of families reported in the literature to over 50.
Part V starts with a chapter by Guerrini et al. that focuses primarily on the fascinating group of disorders in which there are genetically determined abnormalities of brain structure. This includes major syndromes such as tuberous sclerosis complex (TSC), together with the cortical dysgeneses and neuronal migration disorders such as lissencephaly, subcortical band heterotopia and bilateral periventricular nodular heterotopia. This field is moving very fast, and there is unfortunately, but inevitably, no discussion of the recently identified X-chromosome genes doublecortin and filamin. In Chapter 16, McLachlan and Bulman provide an interesting discussion of the genetics of febrile convulsions and temporal lobe epilepsy and their tortuous and still unresolved relationship. The remaining chapters provide useful overviews of reading epilepsy and hot-water epilepsy.
Part VI is a feast for afficionados of `molecular medicine'. Ortrud Steinlein gives an authoritative overview of her discoveries relating to the molecular basis of autosomal dominant nocturnal frontal lobe epilepsy, and in the following Chapter Buisson and co-workers put this in context with a review of neuronal nicotinic acetylcholine receptors. In Chapter 21, Ptác
ek reviews the role of ion channels in paroxysmal disorders of the nervous system, which again provides vital background information to the emerging concept of idiopathic epilepsies as ion channelopathies. Lastly, in Chapter 22, Boncinelli and his co-workers describe the role of homeobox genes such as Otx and Emx in the developing brain in relation to the recent identification of Emx2 mutations in schizencephaly.
Part VII is devoted to animal models in mice, gerbils and rats. Seyfried et al. in Chapter 23 provide an update on the EL mouse, a model of particular relevance and importance in view of its multifactorial mode of inheritance. Evidence that the seizure-sensitive gerbil has abnormal circuitry in the hippocampal formation is provided by Peterson and Ribak in Chapter 24, and work in genetically epilepsy-prone rats identifying convulsive seizure circuitry in forebrain and brainstem is presented in Chapter 25 by Jobe et al. In Chapter 26, there is a brief review by Toth of the burgeoning field of transgenic mouse models of epilepsy; and finally, in Chapter 27 deLorey and co-workers discuss the interesting relationships seen between the epilepsy observed in the GABAA receptor ß3 subunit knockout mouse and the epilepsy which occurs in Angelman syndrome (AS). Seizure disorders occur in 90% of AS probands, and large deletions in AS include a cluster of GABAA receptor genes. The work described provides the first evidence that impaired GABAergic neurotransmission can produce epilepsy.
Finally, Sam Berkovic, who has done so much to advance knowledge in this area provides a thoughtful `Afterword' in which he muses on some of the novel concepts that have emerged and provided a final update on the latest advances.
It is rare to find a book which fuses clinical and scientific knowledge in such a clear and exciting way. It deserves a place in the library of any neurologist interested in epilepsy, and any neuroscientist interested in the human implications of molecular neurobiology.
Notes
Edited by S. F. Berkovic, P. Genton, E. Hirsch and F. Picard. 1999. Pp. 286. London: John Libbey & Company Limited. Price £59.00. ISBN 0-86196-569-8.
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