Robinsoe Crusoe, NFXL1, and speech delay

Founder variant. Specific language impairment (SLI) is a common neurodevelopmental disorder, presenting as delays in acquiring language skills in children who have no hearing loss or other developmental delays. There is a strong genetic component, but the genetic architecture of SLI is entirely unknown. In a recent publication in PLOS Genetics, exome sequencing is performed in the founder population of the Robinson Crusoe Island where SLI is common. Using a combination of exome sequencing and association study, the autors identify a variant In NFXL1 as a plausible candidate for language delay. Continue reading

ESES and the postsynapse – CNKSR2 in genetic epilepsies

Structure. Despite tremendous advances in understanding its genetic underpinnings in the last few years, electrical status epilepticus during slow-wave sleep (ESES) is a poorly understood neurodevelopmental disorder and to a certain extent the prototype of an epileptic encephalopathy. Slow-wave sleep in affected children is entirely replaced by epileptiform activity, leading to significant neurocognitive impairment with an emphasis on speech impairment. In a recent publication in Annals of Neurology, alterations in CNKSR2 are identified in families with a more severe course of ESES, highlighting the postsynapse as a possible player in ESES pathogenesis. Continue reading

Navigating the epilepsiome – live from Tübingen

2D. I am writing this post during our EuroEPINOMICS meeting in Tübingen listening to presentation from CoGIE, the EuroEPINOMICS project working on IGE/GGE and Rolandic Epilepsies and RES, the project on rare epilepsies. At some point during the afternoon, I made my selection for the best graph during the presentations today – an overview of the conservation space of epilepsy genes. Continue reading

Less is more – gene identification in epileptic encephalopathies through targeted resequencing

Exome no more. Over the last 15 months, we have repeatedly discussed how exome sequencing or genome sequencing is applied to neurodevelopmental disorders in order to discover new candidate genes and to assess the role of known candidate genes. We have also wondered sometimes whether exome sequencing is the most straightforward approach. Now – outpacing the two large international consortia using exome sequencing in epileptic encephalopathies – a recent study in Nature Genetics uses a different approach to uncover the genetic basis in 10% of patients with epileptic encephalopathies.  Targeted resequencing or gene panel analysis is a hybrid technology between candidate gene sequencing and next generation sequencing and focuses only on a subset of candidate genes. While their study provides a comprehensive overview over the genetics of rare epilepsy syndromes, it raises the question whether the era of large-scale exome sequencing is coming to a natural end. Continue reading

Rolandic Epilepsy Explained?

Soundbites. I am very happy to have been part of the 1st Waterloo Foundation Meeting on the Idiopathic Focal Epilepsies of Childhood, which took place at King’s College in London on September 29th, 2012. This meeting was exclusively dedicated to everything rolandic. While the 10th European Epilepsy Congress is just getting started, we thought that we could provide you with a few soundbites from this meeting. And — by the way — rolandic epilepsy is far from being explained. Continue reading