Towards a Molecular Syndromology of the Epilepsies

thies. After defining the term epileptic encephalopathy and elucidating its complex relationship between epilepsy on the one side and cognitive and neurological impairment on the other, Helbig and Tayoun give a summary of novel insights. By focussing on the complexity of variable genotype-phenotype correlations within diseases underlying these genetic conditions, they outline that the same pathogenic variant in an epilepsy gene can cause epileptic encephalopathy as well as easy to treat or spontaneously resolving epilepsy without intellectual disability. Finally, it is discussed whether these allelic conditions represent a fluid continuum or distinct entities. Besides these aspects, they give a list of responsible genes pointing to disturbed functions of ion channels, neurotransmitter receptors, and presynaptic vesicle processing as main pathophysiological principles underlying epileptic encephalopathies as well as more benign forms of epilepsy. Syrbe et al. illustrate the great phenotypic variability of a given genetic variant. They present a family with a novel SCN2A missense variant associated with phenotypes ranging from benign familial neonatal infantile seizures to Ohtahara syndrome. Gene expression studies in Xenopus laevis oocytes could not explain this variability of phenotypes associated with this specific variant taking into account that dysfunctional channel subDuring the past decade, there has been remarkable progress in elucidating the genetic basis of epilepsy disorders. This is due to new genome-wide technologies allowing us to screen for small copy number variants as well as for alterations of the DNA base sequence. This technical progress relieves clinicians from the urge of hypothesising about defined genetic causes and speculating about variations in a restricted number of genes or diverse chromosomal abnormalities. Furthermore, we have learnt a lot about the genetic architecture of the epilepsies and its pathophysiological principles. This especially holds true for rare diseases with epileptic seizures as a phenotypic feature. However, some important open questions remain unaddressed. For example, the complexity of genotype-phenotype correlations in these rare disorders is poorly understood [Steinlein, 2014], and the genetic background of common genetic epilepsies still remains unclear [Pal and Strug, 2014]. Despite these and other unresolved issues, one may ask whether our present knowledge allows us to outline some aspects of a molecular syndromology of the epilepsies. This themed issue of Molecular Syndromology tries to address diverse and frequent genetic aspects of epileptogenesis without the intention of being exhaustive. The methodological progress of the past years is nicely illustrated by the example of epileptic encephalopaPublished online: August 17, 2016