Network Of Clinical Research Studies On Craniosynostosis, Skull Malformations With Premature Fusion Of Skull Bones

Active, not recruiting

• Conditions: Craniosynostosis
• Interventions: Other: Craniosynostosis Network Environmental Survey; Other: 2D/3D Photography; Procedure: Buccal Swab Cell Sampling; Procedure: Blood sampling; Procedure: Skin Biopsy; Procedure: Tissues from a Clinically Indicated Procedure; Procedure: Pre-operative CT Scan Image Files.

• Registration Number: NCT03025763
• Lead Sponsor: Icahn School of Medicine at Mount Sinai

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.

Detailed Description

The long-term goal of the Program Project, Craniosynostosis Network, is to elucidate normal and abnormal craniofacial biology to ultimately improve the treatment of craniofacial disorders. Craniosynostosis and other skull abnormalities are among the most common human malformations usually requiring surgical and medical intervention. The Network will integrate three projects and two cores. Scientists with diverse expertise including anthropology, morphometry, imaging, birth defects, developmental biology, genetics, genomics, epidemiology, statistics, and systems biology will explore the determinants of the fate of the relevant mesenchymal progenitor cells, abnormalities in osteogenesis that contribute to global skull growth abnormality and premature closure of cranial sutures, especially the coronal suture. High quality genomic data will be obtained from patients with coronal nonsyndromic craniosynostosis (cNSC) and their available parents. Novel genome-wide variant-, gene- and network-level analyses will be performed on these families to identify novel variants and genetic regions associated with coronal craniosynostosis.

This study is a multi-center, open-enrollment, retrospective study, employing both family-based and case-control study designs.

Approximately 4000 cNSC patients, their family members, and controls will be recruited by Icahn School of Medicine at Mount Sinai and the majority will be recruited from the more than 10 collaborating institutions worldwide.

Basic Information
|
Recruitment & Eligibility
|
Study & Design
|
Trial Locations

Study Timeline

• Study Start: 2015-01-13
• Study First Submitted: 2017-01-17
• Study First Submitted QC: 2017-01-17
• Study First Posted: 2017-01-20
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-31
• Last Update Posted: 2025-01-02
• Primary Completion: 2028-01-31
• Study Completion: 2028-01-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 2145

Inclusion Criteria

• Cases with diagnosis of coronal
• Unaffected relatives of cases
• Unaffected controls including those who may have undergone clinically indicated craniofacial surgery for trauma or conditions other than craniosynostosis or bone disease. These individuals will be recruited at some of the other collaborating institutions, but not at Mount Sinai.

Individuals of any racial or ethnic group with the established or suspected clinical diagnosis of coronal, nonsyndromic craniosynostosis will be included in this study. Unaffected relatives, such as their biological parents and/or sibs, will also be included to contribute medical information and samples as negative controls for our study.

Read More

Exclusion Criteria

• Those who fit the criteria, but who choose not to participate
• Those who do not meet the criteria.
• Other than children, no vulnerable individuals will be recruited, such as intellectual impaired individuals or prisoners.

Read More

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Coronal Nonsyndromic Craniosynostosis, trios	Craniosynostosis Network Environmental Survey	Participants with diagnosis of coronal, nonsyndromic craniosynostosis including affected and unaffected biological parents
Coronal Nonsyndromic Craniosynostosis, trios	2D/3D Photography	Participants with diagnosis of coronal, nonsyndromic craniosynostosis including affected and unaffected biological parents
Coronal Nonsyndromic Craniosynostosis, trios	Buccal Swab Cell Sampling	Participants with diagnosis of coronal, nonsyndromic craniosynostosis including affected and unaffected biological parents
Coronal Nonsyndromic Craniosynostosis, trios	Blood sampling	Participants with diagnosis of coronal, nonsyndromic craniosynostosis including affected and unaffected biological parents
Coronal Nonsyndromic Craniosynostosis, trios	Skin Biopsy	Participants with diagnosis of coronal, nonsyndromic craniosynostosis including affected and unaffected biological parents
Coronal Nonsyndromic Craniosynostosis, trios	Tissues from a Clinically Indicated Procedure	Participants with diagnosis of coronal, nonsyndromic craniosynostosis including affected and unaffected biological parents
Coronal Nonsyndromic Craniosynostosis, trios	Pre-operative CT Scan Image Files.	Participants with diagnosis of coronal, nonsyndromic craniosynostosis including affected and unaffected biological parents
Coronal, nonsyndromic craniosynostosis	Craniosynostosis Network Environmental Survey	Participants with coronal, nonsyndromic craniosynostosis when biological parents are not available
Coronal, nonsyndromic craniosynostosis	2D/3D Photography	Participants with coronal, nonsyndromic craniosynostosis when biological parents are not available
Coronal, nonsyndromic craniosynostosis	Tissues from a Clinically Indicated Procedure	Participants with coronal, nonsyndromic craniosynostosis when biological parents are not available
Coronal, nonsyndromic craniosynostosis	Pre-operative CT Scan Image Files.	Participants with coronal, nonsyndromic craniosynostosis when biological parents are not available
Unaffected controls	Blood sampling	Unaffected controls who may have undergone clinically indicated craniofacial surgery for trauma or conditions other than craniosynostosis or bone disease
Unaffected controls	Skin Biopsy	Unaffected controls who may have undergone clinically indicated craniofacial surgery for trauma or conditions other than craniosynostosis or bone disease
Coronal, nonsyndromic craniosynostosis	Buccal Swab Cell Sampling	Participants with coronal, nonsyndromic craniosynostosis when biological parents are not available
Coronal, nonsyndromic craniosynostosis	Blood sampling	Participants with coronal, nonsyndromic craniosynostosis when biological parents are not available
Coronal, nonsyndromic craniosynostosis	Skin Biopsy	Participants with coronal, nonsyndromic craniosynostosis when biological parents are not available
Unaffected controls	Craniosynostosis Network Environmental Survey	Unaffected controls who may have undergone clinically indicated craniofacial surgery for trauma or conditions other than craniosynostosis or bone disease
Unaffected controls	2D/3D Photography	Unaffected controls who may have undergone clinically indicated craniofacial surgery for trauma or conditions other than craniosynostosis or bone disease
Unaffected controls	Buccal Swab Cell Sampling	Unaffected controls who may have undergone clinically indicated craniofacial surgery for trauma or conditions other than craniosynostosis or bone disease
Unaffected controls	Tissues from a Clinically Indicated Procedure	Unaffected controls who may have undergone clinically indicated craniofacial surgery for trauma or conditions other than craniosynostosis or bone disease
Unaffected controls	Pre-operative CT Scan Image Files.	Unaffected controls who may have undergone clinically indicated craniofacial surgery for trauma or conditions other than craniosynostosis or bone disease

Primary Outcome Measures

Name	Time	Method
Phenotype-genotype gene expression correlations	up to 5 years	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.

Secondary Outcome Measures

Name	Time	Method
Incidence of gene mutations	up to 5 years	gene mutations and variants may be found that are significantly associated with coronal nonsyndromic craniosynostosis

Trial Locations

Locations (20)

Johns Hopkins University; 🇺🇸 Baltimore, Maryland, United States

Ann & Robert H. Lurie Children's Hospital of Chicago; 🇺🇸 Chicago, Illinois, United States

National Birth Defects Prevention Study at University of Iowa; 🇺🇸 Iowa City, Iowa, United States

Birth Defect Registries of New York State; 🇺🇸 Albany, New York, United States

Icahn School of Medicine at Mount Sinai; 🇺🇸 New York, New York, United States

The International Craniosynostosis Consortium at University of California at Davis; 🇺🇸 Davis, California, United States

Yale University; 🇺🇸 Hartford, Connecticut, United States

New York University; 🇺🇸 New York, New York, United States

Pennsylvania State University; 🇺🇸 University Park, Pennsylvania, United States

Medical City Children's Hospital; 🇺🇸 Dallas, Texas, United States

Pennsylvania State Milton S. Hershey Medical Center; 🇺🇸 Hershey, Pennsylvania, United States

University of Texas at Southwestern; 🇺🇸 Dallas, Texas, United States

University of Bordeaux; 🇫🇷 Talence, Aquitaine, France

INSERM/ Hospital Necker-Enfants Malades; 🇫🇷 Paris, Cedex 14, France

University Hospital Heidelberg; 🇩🇪 Heidelberg, Germany

Hospital Sant Joan de Deu; 🇪🇸 Barcelona, Esplugues De Llobregat, Spain

Oxford University; 🇬🇧 Oxford, Oxfordshire, United Kingdom

Boston Children's Hospital; 🇺🇸 Boston, Massachusetts, United States

Seton Family of Hospitals; 🇺🇸 Austin, Texas, United States

University of Utah; 🇺🇸 Salt Lake City, Utah, United States