The Genetics of Brain Malformations

This chapter overviews emerging mechanistic groups and their role in brain development and disease. Microcephaly is a disorder in which the brain is disproportionately smaller than the body and is diagnosed by measuring a head circumference more than two standard deviations lower than the population average. It also discusses similar other brain malformations, microcephaly has proven genetically heterogeneous leading to the identification of numerous genes in patients with indistinguishable phenotype. Analysis of the first genetic locus for primary microcephly, MCPH1, identified mutations in a gene involved in chromosome condensation and DNA damage response. In addition to primary microcephaly, WDR62 mutations cause reduced brain size associated with a wide spectrum of other malformations such as lissencephaly (smooth brain) and pachygyria (few gyri), as well as polymicrogyria (many small gyri) and schizencephaly (split brain). The genetic architecture of every malformation and to be able to provide a genetic diagnosis for every patient.