The New Findings in the Genetics and Pathology of Structural Brain Diseases

Abstract

Many disorders involving the cerebral hemispheres have been identified and classified; however, in the last five years, significant progress has been made in the identification of genes involved in hindbrain development. Space constraints prohibit an exhaustive review of genetics of brain malformations encountered in the newborn. Rather, this review will address malformations of the corpus callosum, one of the more common malformations, and the hindbrain disorders, a less common entity. Neuroimaging of the brain is often one of the first steps in the determination of etiology and prognosis of an encephalopathic condition in the newborn. Structural anomalies of the brain are seen with some frequency in this setting. Due to the complex nature of cortical development, both genetic and non-genetic (environmental, toxins, etc.) factors may lead to a very similar pattern on MRI. In recent years, given the advances in genetic sequencing technologies as well as improvements in neuroimaging field, clarity, and technical advances in imaging sick and small infants, progress has been made to identify the genetic underpinnings of many cortical malformations. This has been particularly the case with regard to posterior fossa abnormalities. Congenital malformations of the posterior fossa are relatively rare but are frequently more recognized, given the continuous improvements of neuroimaging. High-resolution genetic testing has led to identification of the etiology for some, but the cause of many still is elusive. Future application of high-resolution genetic testing such as whole exome sequencing will help identify other variants. MRI patterns may not sufficiently differentiate the clinical entities.