{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T05:44:39Z","timestamp":1791092679100,"version":"4.1.0"},"reference-count":50,"publisher":"American Academy of Pediatrics (AAP)","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,8,1]]},"abstract":"<jats:sec>\n                    <jats:title>OBJECTIVES:<\/jats:title>\n                    <jats:p>We describe the first cohort-based analysis of the impact of genetic disorders in craniosynostosis. We aimed to refine the understanding of prognoses and pathogenesis and to provide rational criteria for clinical genetic testing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>We undertook targeted molecular genetic and cytogenetic testing for 326 children who required surgery because of craniosynostosis, were born in 1993\u20132002, presented to a single craniofacial unit, and were monitored until the end of 2007.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>Eighty-four children (and 64 relatives) had pathologic genetic alterations (86% single-gene mutations and 14% chromosomal abnormalities). The FGFR3 P250R mutation was the single largest contributor (24%) to the genetic group. Genetic diagnoses accounted for 21% of all craniosynostosis cases and were associated with increased rates of many complications. Children with an initial clinical diagnosis of nonsyndromic craniosynostosis were more likely to have a causative mutation if the synostoses were unicoronal or bicoronal (10 of 48 cases) than if they were sagittal or metopic (0 of 55 cases; P = .0003). Repeat craniofacial surgery was required for 58% of children with single-gene mutations but only 17% of those with chromosomal abnormalities (P = .01).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>Clinical genetic assessment is critical for the treatment of children with craniosynostosis. Genetic testing of nonsyndromic cases (at least for FGFR3 P250R and FGFR2 exons IIIa\/c) should be targeted to patients with coronal or multisuture synostoses. Single-gene disorders that disrupt physiologic signaling in the cranial sutures often require reoperation, whereas chromosomal abnormalities follow a more-indolent course, which suggests a different, secondary origin of the associated craniosynostosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1542\/peds.2009-3491","type":"journal-article","created":{"date-parts":[[2010,7,19]],"date-time":"2010-07-19T20:35:53Z","timestamp":1279571753000},"page":"e391-e400","source":"Crossref","is-referenced-by-count":259,"title":["Prevalence and Complications of Single-Gene and Chromosomal Disorders in Craniosynostosis"],"prefix":"10.1542","volume":"126","author":[{"given":"Andrew O. 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