Researchers have discovered a new epilepsy disorder caused by a gene which had not previously been linked to epilepsy. The syndrome, named cortical dysplasia-focal epilepsy (CDFE), includes severe epilepsy, some autistic traits, mental retardation and aggressive behaviour.

CDFE was discovered in nine children who are all closely-related members of the Old Order Amish community in Pennsylvania, USA. Their seizures began between the ages of 14 and 20 months, at which point their learning ability and behaviour deteriorated. Scans showed abnormal development in several parts of the brain.

CDFE is linked to a mutation in a gene called CNTNAP2. This controls a protein called CASPR2 which is important in maintaining contact between different types of brain cell (neurones and glial cells) in adults. In patients with CDFE, this protein is present in abnormally low amounts. This is the first time this protein has been found to be important in children, whose brains are still developing. It may control the way cells interact at important stages in the development of the adult brain.

Everybody inherits two copies of the CNTNAP2 gene, one from each parent. All the children with CDFE had the same mutation in both their copies of the gene. Their parents each had one mutated version and one normal version, and did not have epilepsy. Genetic studies of another eighteen patients from the same Amish community who had previously been diagnosed with epilepsy showed that they also all had two mutated copies of the CNTNAP2 gene and had CDFE syndrome.

Dr Kevin Strauss and his team at the Clinic for Special Children in Strasburg, Pennsylvania, USA, predicted that mutations in the way the protein CASPR2 is present in the brain would also be found in children from other populations who had epilepsy syndromes including mental retardation and autism. In their paper, published on 30 March in the New England Journal of Medicine, they noted that the CASPR2 protein had not previously been shown to be important for brain development from tests in cell cultures, but that this study showed compelling evidence of its involvement in these fundamental processes. Identifying this genetic mutation in new patients may also allow doctors to treat infants before they start to show symptoms of the syndrome, which may improve their progress in the long term.

The Epilepsy Research Foundation (now called Epilepsy Research UK) recently organised an international expert workshop on aspects of genetics and epilepsy. A report of the workshop will be published later this year. This is a hot topic in epilepsy research at the moment, as scientists begin to understand the very complex interaction between our many genes and our surroundings and life events that can result in epilepsy.

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