Clinical Project 1: Longitudinal Natural History Study of Syndromic Craniosynostosis

Children'S Hosp Of Philadelphia, Philadelphia PA

Investigators

Abstract

ABSTRACT: CLINICAL PROJECT 1 Syndromic craniosynostosis (CS) encompasses a set of rare diseases characterized by premature ossification of the cranial sutures, leading to cranial vault distortion and constriction of the growing brain in pediatric patients. While CS syndromes have become more genetically defined, much remain unknown about how pathogenic variants correlate with natural history of CS. The Advancing Craniosynostosis Treatment (ACT) Rare Diseases Consortium establishes a multi-institutional collaboration between leading craniofacial centers to address key gaps in knowledge for syndromic CS natural history and clinical management. In Clinical Project 1 (CP1), we will describe the longitudinal natural history for 5 types of CS syndromes: Apert, Pfeiffer, Crouzon, Muenke and Saethre-Chotzen. This proposal tests the central hypothesis that multi-modal integration of longitudinal genomic, morphometric, neurocognitive, psychological, and patient reported data will yield a comprehensive understanding of the natural history that will predict disease progression and response to treatment for syndromic CS patients. This study will be the largest and most comprehensive prospective multi-site study of syndromic CS to date, with the following aims: 1) utilize deep phenotyping, molecular diagnosis, and multi-modal integration with the electronic medical record to characterize syndromic CS progression over time, 2) evaluate the neuro-cognitive and psychosocial outcomes of syndromic craniosynostosis and correlate outcomes with clinical history and 3) collect FACE-Q and FACE-Q Kids with a patient-reported outcomes dashboard that can be used across all patients with syndromic CS. Together, this study will integrate multi-modal objective measures to correlate genotype to phenotype in the 5 CS syndromes. CP1 will validate methodologies and provide the context with which medical and surgical treatments can be objectively measured. The broad impact of this work is to generate the foundational data that will inform future clinical studies and trials that will establish clinical standards and best practices that will enhance health outcomes, determine best practices, and ultimately enhance health outcomes for syndromic CS patients.