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The fact that there are likely to be subtypes of ASD has complicated attempts to develop effective therapies. The UC Davis MIND Institute Autism Phenome Project is a longitudinal, multidisciplinary analysis of children with autism and age\u2010matched typically developing controls; nearly 400 families are participating in this study. The overarching goal is to gather sufficient biological, medical, and behavioral data to allow definition of clinically meaningful subtypes of ASD. One reasonable hypothesis is that different subtypes of autism will demonstrate different patterns of altered brain organization or development i.e., different neurophenotypes. In this Commentary, we discuss one neurophenotype that is defined by megalencephaly, or having brain size that is large and disproportionate to body size. We have found that 15% of the boys with autism demonstrate this neurophenotype, though it is far less common in girls. We review behavioral and medical characteristics of the large\u2010brained group of boys with autism in comparison to those with typically sized brains. While brain size in typically developing individuals is positively correlated with cognitive function, the children with autism and larger brains have more severe disabilities and poorer prognosis. This research indicates that phenotyping in autism, like genotyping, requires a very substantial cohort of subjects. Moreover, since brain and behavior relationships may emerge at different times during development, this effort highlights the need for longitudinal analyses to carry out meaningful phenotyping. <jats:italic><jats:bold>Autism Res<\/jats:bold> 2017, 10: 711\u2013722<\/jats:italic>. \u00a9 2017 International Society for Autism Research, Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/aur.1755","type":"journal-article","created":{"date-parts":[[2017,2,27]],"date-time":"2017-02-27T05:28:43Z","timestamp":1488173323000},"page":"711-722","source":"Crossref","is-referenced-by-count":88,"title":["In pursuit of neurophenotypes: The consequences of having autism and a big brain"],"prefix":"10.1002","volume":"10","author":[{"given":"David G.","family":"Amaral","sequence":"first","affiliation":[{"name":"MIND Institute, UC Davis 2825 50th Street Sacramento 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