CLINICAL GENETICS OF CRANIOSYNOSTOSIS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Specific Aims/ Objectives General: This study is part of a collaborative consortium of multidisciplinary teams at the John Hopkins Hospital, Children's Hospital Boston, Children's Hospital of Philadelphia, and the Pennsylvania State University to perform comprehensive clinical evaluations of craniosynostosis patients in order to develop well-characterized proband population. Craniosynostosis, the premature fusion of one or more skull sutures, is a clinically heterogeneous condition of complex etiology and pathogenesis occurring in 1 out of 2,000 live births. While there are more than 100 dysmorphic syndromes that manifest craniosynostosis as a major phenotypic feature, approximately 85% of cases are believed to be nonsyndromic. Progress is beginning to be made in understanding the clinical and molecular aspects of monogenic syndromic craniosynostosis, the characterization of nonsyndromic craniosynostosis (NSC) is incomplete and little is known about the anthropometric profile of the craniosynostic skull. Reports of unrecognized cases of increased intracranial pressure (ICP) and a high prevalence of Chiari I malformation in metopic NSC patients suggest that the clinical care of these patients could be improved. Developmental delay and/or learning disabilities are also present in a significant portion of the patient population and cognitive outcome is directly associated with the extracranial anomalies, gene mutations, and the specific anthropometric parameter. Further characterization of multiple organ systems involvement and neuropsychiatric profile of craniosynostosis is also needed. The systematic evaluation of a large group of carefully categorized patients will allow the unbiased ascertainment of the clinical and anthropometric features of specific sutural synostosis, genotypic/phenotypic variability, and specific developmental baseline profiles. The accumulation of varied data sets from well-characterized, clinically homogeneous populations, and a specim