Relative to germline mutations, somatic mutations can lead to milder cases of heritable neurodevelopmental disorders. For example, somatic mutations in genes involved in neuronal migration are estimated to represent 5 to 10% of de novo mutations and are detected more frequently in patients with unexplained brain malformations when studied with sensitive high-throughput sequencing methods (55). Moreover, somatic mutations within the LIS1 or DCX genes can lead to gross disruptions of neuronal migration, whereas germline mutations in LIS1 or DCX result in lissencephaly (56, 57). Results from several experiments also suggest that somatic mutations that lead to a reduction of gene copy number in migrating neurons can lead to cell-autonomous defects in neuronal migration, with severe epilepsy and intellectual disability as a consequence (56, 57).
