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The hypothesized association between single-suture craniosynostosis and neurodevelopment remains unclear, given the methodologic limitations of previous studies, most notably the absence of control groups.Standardized measures were used to assess the neurodevelopment of 125 matched case-control pairs shortly after cases were first diagnosed with isolated fusions of the sagittal, metopic, lambdoid, or right or left coronal sutures. Participants varied in age from 2 to 24 months.Cases had significantly lower mean standardized scores than controls on measures of cognitive ability and motor functioning (p < 0.02). These differences were unaffected by the location of synostosis, age of diagnosis, infant sex, and maternal IQ. Measures of early language functions revealed no group differences.Before cranioplasty, single-suture craniosynostosis is associated with modest but reliable neurodevelopmental delays that cannot be attributed to maternal intelligence and family sociodemographic variables. Follow-up of this sample will determine the predictive significance of these delays. In the meantime, routine neurodevelopmental screening of infants with isolated craniosynostosis is recommended.