Neurodevelopmental disorders (NDDs) manifest mostly as developmental delay in early childhood and lead to intellectual disability later in life. Some 2-3% of the population is affected. NDDs are a significant burden to affected individuals and their families and a major unsolved medical challenge. In the majority of cases single gene defects are thought to be the underlying cause. Scientific advances during the last years have allowed identifying such a genetic defect in about half of all cases. By now, more than 1,500 causative genes have been identified. Research groups at the Institute have made important contributions to these advancements and identified several such genes and characterized the associated syndromes. In Germany, the major cause of NDDs is newly arisen gene mutations acting in autosomal dominant manor. In consanguineous families, though, autosomal recessive variants inherited from both parents are the most frequent cause. Mutations in genes located on the X-chromosome are also known with variable expression in both genders.
Clinical genetic diagnosis is hampered by the enormous genetic heterogeneity and an often unspecific clinical presentation. Novel methods of genome sequencing (next generation sequencing) have paved the way to simultaneously investigate the entire genome or parts of it. This technology is intensively used at the Institute, especially in parent-child trio design for identification of de novo Mutations, but also in consanguineous families using autozygosity mapping for the detection of recessive variants. To better understand the pathophysiology of NDDs we investigate candidate genes using cell biology models with induced pluripotent cells but also using the fruitfly animal model (drosophila). In addition, Prof. Zweier curates the SysID database, a systematic catalogue of all published NDD associated genes. Finally, we have characterized the clinical and mutational spectrum of a number of syndromal and non-syndromal NDDs.