Issue 8/2015. This week’s review of the relevant publications in the field is about a novel risk factor for focal epilepsies, a gene involved in mRNA transport from the cell nucleus, and a small, confirmatory study on exome sequencing in Infantile Spasms.
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
GRIN2A. Mutations in several genes coding for NMDA receptor subunits have recently been found in various neurodevelopmental disorders. Amongst the different genes, GRIN2A is one of the most prominent ones and mutations in this gene are found in patients with epilepsy-aphasia syndromes. So far, we have mainly looked at GRIN2A from the epilepsy side. In a recent publication in Neurology, Turner and collaborators now examine the speech phenotype in GRIN2A families. They examine two families where speech issues are a prominent phenotypic feature. It turns out that GRIN2A mutations may predispose to a distinct speech phenotype. Continue reading
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