Brief Summary

Craniosynostosis (CS) is a common malformation occurring in \~4 per 10,000 live births in which the sutures between skull bones close too early, causing long-term problems with brain and skull growth. Infants with CS typically require extensive surgical treatment and may experience many perioperative complications, including hemorrhage and re-synostosis. Even with successful surgery, children can experience developmental and learning disabilities or vision problems. Most often, CS appears as isolated nonsyndromic CS (NSC). Of the several subtypes of CS, unilateral or bilateral fusion of the coronal suture is the second most common form of CS accounting for 20-30% of all NSC cases. The etiology of coronal NSC (cNSC) is not well understood, although the published literature suggests that it is a multifactorial condition. About 5-14% of coronal craniosynostosis patients have a positive family history, with a specific genetic etiology identified in \>25% of cNSC cases, suggesting a strong genetic component in the pathogenesis of this birth defect. The causes for cNSC and its phenotypic heterogeneity remain largely unknown. An international team of investigators will generate large genomic and gene expression datasets on samples from patients with cNSC. State-of-the-art imaging, genetic, and developmental and systems biology approaches will be used to quantitatively model novel pathways and networks involved in the development of cNSC. Novel variant-, gene- and network-level analyses will be performed on the genomic data obtained from cNSC cases, their relatives, and controls to identify novel variants and genetic regions associated with cNCS. Quantitative, analytical, and functional validations of these predictions will provide insights into the etiology and possible therapeutic targets for CS and potentially other bone-related disorders.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

2,145

participants targeted

Target at P75+ for all trials

Timeline

21mo left

Started Jan 2015

Longer than P75 for all trials

Geographic Reach

5 countries

20 active sites

Status

active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

13.1 years study duration

Study Progress87%

Jan 2015Jan 2028

Study Start

First participant enrolled

January 13, 2015

Completed

2 years until next milestone

First Submitted

Initial submission to the registry

January 17, 2017

Completed

3 days until next milestone

First Posted

Study publicly available on registry

January 20, 2017

Completed

11 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 31, 2028

Expected

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 31, 2028

Last Updated

January 2, 2025

Status Verified

December 1, 2024

Enrollment Period

13.1 years

First QC Date

January 17, 2017

Last Update Submit

December 31, 2024

Conditions

Craniosynostosis

Keywords

CraniosynostosisBoneBirth DefectCongenital AnomalyMalformationGeneticsGenomicsSkullHumanMouseImagingCell BiologyInduced Pluripotent Stem CellsSystem Biology

Outcome Measures

Primary Outcomes (1)

Phenotype-genotype gene expression correlations
Phenotype-genotype-gene expression correlations among cohorts of cases of coronal nonsyndromic craniosynostosis and genotype-gene expression correlations among controls will be analyzed and compared.
up to 5 years

Secondary Outcomes (1)

Incidence of gene mutations
up to 5 years

Study Arms (3)

Coronal Nonsyndromic Craniosynostosis, trios

Participants with diagnosis of coronal, nonsyndromic craniosynostosis including affected and unaffected biological parents

Other: Craniosynostosis Network Environmental SurveyOther: 2D/3D PhotographyProcedure: Buccal Swab Cell SamplingProcedure: Blood samplingProcedure: Skin BiopsyProcedure: Tissues from a Clinically Indicated ProcedureProcedure: Pre-operative CT Scan Image Files.

Coronal, nonsyndromic craniosynostosis

Participants with coronal, nonsyndromic craniosynostosis when biological parents are not available

Unaffected controls

Unaffected controls who may have undergone clinically indicated craniofacial surgery for trauma or conditions other than craniosynostosis or bone disease

Interventions

Craniosynostosis Network Environmental SurveyOTHER

Questionnaire is administered to the mothers of affected participants regarding medical history and environmental exposures during pregnancy, delivery, and neonatal period. Optional.