Even before he was born, it was clear that the boy’s brain was unusual—so much so that his expecting parents flew from rural Alaska to Seattle, where specialists could attend to their son from birth. That is how James Bennett first met the boy, then a days-old infant struggling to breathe. The baby’s head was too big. The structures in his brain looked wrong. Bennett, a pediatric geneticist at Seattle Children’s, was tasked with figuring out why.
The answer was ultimately stranger than doctors could have imagined: The boy’s brain was missing an entire type of cell, called microglia, the result of mutations in a single gene, called CSF1R. Doctors had never seen anything like it.
Microglia make up 10 percent of the brain’s cells, but they are not neurons and therefore have long been overlooked. The boy’s case makes their importance unmistakable. In the absence of microglia, the boy’s neurons still grew to fill his skull, but they ended up in the wrong places and made the wrong connections. Microglia, scientists have started to realize, guide the development of the brain.
“There wasn’t any part of the brain that wasn’t involved and affected in this child,” Bennett says. A part of the baby’s cerebellum jutted at an odd angle. His ventricles, normally small fluid-filled cavities in the brain, were too large. And a dense bundle of nerves that is supposed to connect the brain’s left and right hemispheres, called the corpus callosum, had entirely failed to develop.