Kiel: Innovative Genetic Testing for Children with Developmental Disorders and Epilepsy

A recent study with significant involvement from the University of Kiel (University of Kiel) shows what genetic changes cause developmental disorders and epilepsy. The results can dramatically improve common genetic testing today. In addition, the international research team, including the Kiel Working Group on Genetics of Epilepsy in the Department of Pediatrics II (Director: Professor Ulrich Stephani) of the Schleswig-Holstein University Medical Center (UKSH), Campus Kiel, belongs to Professor Ingo Helbig, Patients can benefit from such improved tests as they can be used to obtain targeted and effective treatment. The study was recently published in the prestigious journal Nature Genetics.

In the Meta study, scientists studied an exceptionally large number of cases worldwide. This has been possible thanks to the close cooperation of many international cooperation partners, including Kiel, Antwerp, Boston, London and Tübingen. The researchers badyzed data from 6,753 trios: children with different neurodevelopmental disorders and their mothers and fathers in good health. 1,942 of these children also had a diagnosis of epilepsy. In these parent-child trios, the nearly complete genome was examined, representing approximately 22,000 genes. The researchers looked for changes in the genome, which are badociated with the simultaneous occurrence of developmental disorders and epilepsy. In 33 genes, they frequently found corresponding point mutations and were thus able to identify these genes as important genes for epilepsy.

The most important result of the study is a list of 33 genes badociated with the development of epileptic symptoms. Many of these genes were previously unknown in this context. With the help of the list, the genetic diagnosis in children with developmental disorders and epilepsy can be fundamentally improved, says Professor Johannes Lemke of the Institute of Human Genetics of the University Hospital of Leipzig : The list is a first step towards the recommendation of genes for epilepsy. should be selected in the future. Thus, our research results have great potential for increasing diagnostic performance.

The current work is based on the joint badysis of large datasets that have been built through various research projects over the years. The Kiel Epilepsy Genetics Research Group led by Professor Ingo Helbig played a key role in data preparation and badysis. She has been studying the factors of epilepsy for more than ten years. The methodological focus is on high throughput sequencing and in particular trio-exome sequencing (study of the child and both parents). The drug is becoming more and more digital. Our current study shows how we can more and more acquire new knowledge from the joint badysis of large datasets. It also becomes clear how important it is, especially for rare neuropediatric conditions, to be leaders in the application of modern computer science. Helbig describes new diagnostic options for our patients that enable targeted treatment.

Epilepsy is a very diverse disease. Especially with an additional developmental disorder, genetic causes are often the cause, continues Helbig. Genetic testing is therefore an important diagnostic tool. But currently, each test provider selects according to its own criteria, which genes are examined. The tests are therefore not standardized. Their informative value can vary considerably. Until now, there are no guidelines on the genes for epilepsy that should be tested in such tests. Each provider specifies the design of the so-called gene panels itself. In our study, we were able to show that each of the panels offered up to now covers only half of the relevant genes, adds Lemke.

The method is perfectly suited to researching the causes of epilepsy, confirms the private speaker Hiltrud Muhle. the Paediatrics II Department of the UKSH, Kiel Campus, and the head of the Kiel Pediatric Social Center (SPZ): The genes found now should not be missed in the appropriate gene panel studies. Sooner or later, trio-exom exams should be used diagnostically wider and sooner, the doctor suggests. With this method, a significant proportion of epilepsy can be clarified, particularly in the early onset of the disease and in combinations of epilepsy with developmental disorders. Unnecessary and lengthy examinations can be avoided and individual therapy concepts developed at an early stage.

It is often said that genetic diagnosis has little effect on the treatment of children with intellectual disabilities, autism, or epilepsy. With our study, we prove the opposite. If a genetic cause of developmental disorder with epilepsy has been found, every fourth child can receive a better individual therapy recommendation, says Lemke. For example, many of the genes identified by the study involved ion channels in the brain. These determine the extent to which nerve stimulus transmission works well or poorly. If the flow is disturbed, crises can occur. When the pediatrician learns of such an ion channel disease through a test, he can selectively administer drugs to improve the flow of ions in nerve cells, says the head of the study. So it is sure that the results of the study after publication in Nature Genetics provide a lot of material for further discussion: not only among medical professionals, but also with health insurers, because genetic testing for Therapeutic decisions play an increasingly important role. The study is Dr. med. Henrike Heyne:

De novo variants in neurodevelopmental disorders with epilepsy, https://www.nature.com/articles/s41588-018-0143-7, in Nature Genetics, doi: 10.1038 / s41588- 018-0143-7