Advancing Craniosynostosis Treatment (ACT)Rare Diseases Consortium - ABSTRACT: OVERALL The overall goal of the Advancing Craniosynostosis (ACT) Rare Diseases Consortium is to advance diagnosis, management, and treatment of the 5 types of syndromic craniosynostosis (CS): Apert, Pfeiffer, Crouzon, Muenke, and Saethre-Chotzen. ACT is a highly collaborative, patient-centric, translational, and clinical rare disease consortium. We have assembled a team of multi-disciplinary clinical investigators enhanced by interactions with an external advisory committee and patient advocacy groups. ACT is comprised of 15 investigators with world-leading expertise in genetics, craniofacial surgery, biostatistics, bioinformatics, data science, psychology, and clinical trials from 4 academic pediatric centers around the United States: Children’s Hospital of Philadelphia, Children’s Hospital Los Angeles, Seattle Children’s Hospital, and Boston Children’s Hospital. In addition, we will partner with PEDSnet, a PCORnet clinical research network of 11 leading pediatric hospitals that also include high volume craniofacial centers. The ACT Rare Diseases Consortium will carry out 2 Clinical Projects (CPs), each a prospective multi-site observational study. CP1 will carry out comprehensive longitudinal study of syndromic CS natural history measuring morphologic, neurocognitive, psychological and patient reported outcomes. CP2 will carry out observational comparative cohort study of 3 main types of surgical techniques and timing used to treat cranial vault constriction and increased intracranial pressure in the index operation, and the different surgical techniques and timing used to treat midface dysmorphologies in syndromic CS. In addition, we will operationalize 3 Cores to fulfill the multi-faceted mission of ACT to advance syndromic CS rare disease studies. The Administrative Core will provide an organizational nucleus for committee meetings, compliance oversight, patient registry of medical information, data, analyses, and samples; and communication within ACT and among Rare Diseases Clinical Research Network (RDCRN)-wide activities. The Pilot/Feasibility Governance Core will identify, recruit, vet NIH policies and launch pilot projects that leverage ACT RDC to study key problems in syndromic CS. The Career Enhancement Core will develop clinical research training, team integration, and professional development programs. The near-term deliverable of ACT will be to assemble the infrastructure and personnel to carry out the prospective multi-site studies that will yield the highest-level clinical evidence to inform future comparative studies and clinical treatment standards. The long-term impact of ACT is to significantly improve the health of children with CS through establishing best clinical practices, patient advocacy, piloting novel studies and training the next generation of craniofacial clinicians through ACT and RDCRN.
