2B or not 2B – mutations in GRIN2B and Infantile Spasms

Year of the glutamate receptor. A few months ago we wrote a post about the triplet of Nature Genetics publications that established GRIN2A mutations as a cause of disorders within the epilepsy aphasia spectrum. GRIN2A codes for the NR2A subunit of the NMDA receptor, one of the most prominent neurotransmitter receptors in the Central Nervous System. Now, a recent paper in the Annals of Neurology reports mutations in the GRIN2B subunit as a cause of Infantile Spasms. Interestingly, the functional consequences of these mutations are completely different from GRIN2A-related epilepsies. Continue reading

Copy number variations and the forgotten epilepsy phenotypes

Complexity. Structural genomic variants or copy number variations (CNV) are known genetic risk factors for various epilepsy syndromes. In fact, CNVs might represent the single most studied type of genetic alterations across a very broad range of epilepsy syndromes. There is, however, a group of patients that is usually not investigated in genetic studies: patients with presumable lesional epilepsies or questionable findings on Magnetic Resonance Imaging (MRI). Many of these epilepsies are usually thought to be secondary to the identified lesion, and genetic risk factors are not considered.  In a recent study in the European Journal of Human Genetics last week, we investigated the role of CNVs in a cohort of patients with complex epilepsy phenotypes that were not easily classified into existing categories. Many of patients included had definite or questionable findings on MRI.  The results of our study made us wonder whether the boundary between lesional and genetic epilepsies needs to redrawn. Continue reading

Guilt by association: SCN1A in Temporal Lobe Epilepsy

GWAS. Genome-wide association studies investigate the association of common genetic variants with disease in large patient samples. While this approach has been very successful in many other diseases, the results in epilepsy research have been less convincing. Given the complexity of epilepsy phenotypes, selection of the right epilepsy phenotype has been an ongoing debate. Now, a recent study in Brain finds an intronic variant of the SCN1A gene that is associated with Temporal Lobe Epilepsy (TLE), the most common epilepsy in man. Interestingly, the association with SCN1A seems to be specific for only a particular subtype of focal epilepsies. Continue reading

A metabolic disorder masquerading as adult-onset focal epilepsy

Bella Italia. What a strange day. I am on “emergency duty” for the first day of kindergarten for our daughter. Since the kindergarten is a few meters down the road, I decided to stay home. However, as our windows are currently being replaced, I had nowhere to go. I ended up in a small cafe nearby that I hadn’t noticed before, which turned out to be authentically Italian. Between cornetto e cappuccino, I tried to catch up with some of my blogging duties. For quite some time, I had carried around a case report in the Orphanet Journal of Rare Diseases that I eventually managed to read. In this paper, the authors report on a sib pair with alpha-methylacyl-coA-racemase deficiency (AMACRD). Alpha what?? Exactly. I hadn’t heard of this before, either. However, what raised my interest was the phenotype of one of the patients – adult-onset focal epilepsy. Continue reading