Researchers in this study propose to find genetic causes of several different types of brainstem and cerebellar malformations. Human developmental disorders that involve the brainstem and cerebellum - brain structures derived from the embryonic midbrain and hindbrain - affect a minimum of 2.4 per 1000 resident births based on data from the Centers for Disease Control and Prevention (CDC). Importantly, this large class of disorders co-occurs with more common developmental disorders such as autism, mental retardation, and some forms of infantile epilepsy, and also shares some of the same causes. In this study, researchers will focus on delineating the critical phenotype spectra resulting from malformations in the brainstem and cerebellum and defining the underlying biological networks that are disrupted. Using gene microarrays, the researchers will examine a large cohort of human subjects to find specific genetic mutations that may be involved in mid-hindbrain malformations. The causative genes will be identified using traditional or new high-throughput DNA sequencing methods. The researchers will also try to determine the different biological function of identified genes and protein networks. These studies will contribute immediately to more accurate diagnosis and counseling, and over time may lead to development of specific treatments for a subset of these disorders. Studies of mid-hindbrain development have broad significance for human developmental disorders generally, providing compelling evidence for a connection between cerebellar development and other classes of developmental disorders such as autism, mental retardation, and epilepsy.