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

NCT ID: NCT03025763

Last Updated: 2025-01-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Total Enrollment

2145 participants

Study Classification

OBSERVATIONAL

Study Start Date

2015-01-13

Study Completion Date

2028-01-31

Brief Summary

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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

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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.

Conditions

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Craniosynostosis

Study Design

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Observational Model Type

OTHER

Study Time Perspective

OTHER

Study Groups

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Coronal Nonsyndromic Craniosynostosis, trios

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

Craniosynostosis Network Environmental Survey

Intervention Type OTHER

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

2D/3D Photography

Intervention Type OTHER

Full frontal and lateral face and other parts of the body may be taken for dysmorphic assessment. There is the risk of identification and loss of confidentiality. Optional.

Buccal Swab Cell Sampling

Intervention Type PROCEDURE

One or more swabs, like a Q-tip (for children), or saliva collection kit (for adults) will be used to collect buccal cells. With a swab, they will brush the inside of the mouth several times. With saliva collection kit, they will collect their saliva by spitting into a container several times using a commercially available saliva collection kit. Required.

Blood sampling

Intervention Type PROCEDURE

Venipuncture so that one teaspoon to tablespoons (1-20 ml.) of blood is collected. The volume drawn will be dependent on the age and size of the child. Minimal amounts may be required for DNA, but to establish a lymphoblastoid or iPS cell line at least 3 to 10 ml will be required independent of age. In the case of an infant, if 3 to 10 ml cannot be obtained, then a lymphoblastoid or iPS cell line will not be created. Optional.

Skin Biopsy

Intervention Type PROCEDURE

For those who do not undergo surgery or the skin removal is not considered part of the surgical procedure. After proper cleaning, a piece of skin the size of a pencil eraser (about 4 mm or 1/8 inch in diameter) will be removed (using a circular blade or scalpel) from the arm (inside of arm or forearm in a spot that is as unnoticeable as possible). This area will be covered with a Band-Aid. No stitches are usually required. A crust will form and eventually fall off. Optional.

Tissues from a Clinically Indicated Procedure

Intervention Type PROCEDURE

In some instances when there is discarded tissues and specimens (including skin and bone at the time of reconstructive craniofacial surgery), they will be collected by making arrangements with their physicians. Some of these tissues will be used to generate cell lines. Optional.

Pre-operative CT Scan Image Files.

Intervention Type PROCEDURE

Optional for those who had a previous CT scan for a prior traumatic event.

Coronal, nonsyndromic craniosynostosis

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

Craniosynostosis Network Environmental Survey

Intervention Type OTHER

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

2D/3D Photography

Intervention Type OTHER

Full frontal and lateral face and other parts of the body may be taken for dysmorphic assessment. There is the risk of identification and loss of confidentiality. Optional.

Buccal Swab Cell Sampling

Intervention Type PROCEDURE

One or more swabs, like a Q-tip (for children), or saliva collection kit (for adults) will be used to collect buccal cells. With a swab, they will brush the inside of the mouth several times. With saliva collection kit, they will collect their saliva by spitting into a container several times using a commercially available saliva collection kit. Required.

Blood sampling

Intervention Type PROCEDURE

Venipuncture so that one teaspoon to tablespoons (1-20 ml.) of blood is collected. The volume drawn will be dependent on the age and size of the child. Minimal amounts may be required for DNA, but to establish a lymphoblastoid or iPS cell line at least 3 to 10 ml will be required independent of age. In the case of an infant, if 3 to 10 ml cannot be obtained, then a lymphoblastoid or iPS cell line will not be created. Optional.

Skin Biopsy

Intervention Type PROCEDURE

For those who do not undergo surgery or the skin removal is not considered part of the surgical procedure. After proper cleaning, a piece of skin the size of a pencil eraser (about 4 mm or 1/8 inch in diameter) will be removed (using a circular blade or scalpel) from the arm (inside of arm or forearm in a spot that is as unnoticeable as possible). This area will be covered with a Band-Aid. No stitches are usually required. A crust will form and eventually fall off. Optional.

Tissues from a Clinically Indicated Procedure

Intervention Type PROCEDURE

In some instances when there is discarded tissues and specimens (including skin and bone at the time of reconstructive craniofacial surgery), they will be collected by making arrangements with their physicians. Some of these tissues will be used to generate cell lines. Optional.

Pre-operative CT Scan Image Files.

Intervention Type PROCEDURE

Optional for those who had a previous CT scan for a prior traumatic event.

Unaffected controls

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

Craniosynostosis Network Environmental Survey

Intervention Type OTHER

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

2D/3D Photography

Intervention Type OTHER

Full frontal and lateral face and other parts of the body may be taken for dysmorphic assessment. There is the risk of identification and loss of confidentiality. Optional.

Buccal Swab Cell Sampling

Intervention Type PROCEDURE

One or more swabs, like a Q-tip (for children), or saliva collection kit (for adults) will be used to collect buccal cells. With a swab, they will brush the inside of the mouth several times. With saliva collection kit, they will collect their saliva by spitting into a container several times using a commercially available saliva collection kit. Required.

Blood sampling

Intervention Type PROCEDURE

Venipuncture so that one teaspoon to tablespoons (1-20 ml.) of blood is collected. The volume drawn will be dependent on the age and size of the child. Minimal amounts may be required for DNA, but to establish a lymphoblastoid or iPS cell line at least 3 to 10 ml will be required independent of age. In the case of an infant, if 3 to 10 ml cannot be obtained, then a lymphoblastoid or iPS cell line will not be created. Optional.

Skin Biopsy

Intervention Type PROCEDURE

For those who do not undergo surgery or the skin removal is not considered part of the surgical procedure. After proper cleaning, a piece of skin the size of a pencil eraser (about 4 mm or 1/8 inch in diameter) will be removed (using a circular blade or scalpel) from the arm (inside of arm or forearm in a spot that is as unnoticeable as possible). This area will be covered with a Band-Aid. No stitches are usually required. A crust will form and eventually fall off. Optional.

Tissues from a Clinically Indicated Procedure

Intervention Type PROCEDURE

In some instances when there is discarded tissues and specimens (including skin and bone at the time of reconstructive craniofacial surgery), they will be collected by making arrangements with their physicians. Some of these tissues will be used to generate cell lines. Optional.

Pre-operative CT Scan Image Files.

Intervention Type PROCEDURE

Optional for those who had a previous CT scan for a prior traumatic event.

Interventions

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Craniosynostosis Network Environmental Survey

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

Intervention Type OTHER

2D/3D Photography

Full frontal and lateral face and other parts of the body may be taken for dysmorphic assessment. There is the risk of identification and loss of confidentiality. Optional.

Intervention Type OTHER

Buccal Swab Cell Sampling

One or more swabs, like a Q-tip (for children), or saliva collection kit (for adults) will be used to collect buccal cells. With a swab, they will brush the inside of the mouth several times. With saliva collection kit, they will collect their saliva by spitting into a container several times using a commercially available saliva collection kit. Required.

Intervention Type PROCEDURE

Blood sampling

Venipuncture so that one teaspoon to tablespoons (1-20 ml.) of blood is collected. The volume drawn will be dependent on the age and size of the child. Minimal amounts may be required for DNA, but to establish a lymphoblastoid or iPS cell line at least 3 to 10 ml will be required independent of age. In the case of an infant, if 3 to 10 ml cannot be obtained, then a lymphoblastoid or iPS cell line will not be created. Optional.

Intervention Type PROCEDURE

Skin Biopsy

For those who do not undergo surgery or the skin removal is not considered part of the surgical procedure. After proper cleaning, a piece of skin the size of a pencil eraser (about 4 mm or 1/8 inch in diameter) will be removed (using a circular blade or scalpel) from the arm (inside of arm or forearm in a spot that is as unnoticeable as possible). This area will be covered with a Band-Aid. No stitches are usually required. A crust will form and eventually fall off. Optional.

Intervention Type PROCEDURE

Tissues from a Clinically Indicated Procedure

In some instances when there is discarded tissues and specimens (including skin and bone at the time of reconstructive craniofacial surgery), they will be collected by making arrangements with their physicians. Some of these tissues will be used to generate cell lines. Optional.

Intervention Type PROCEDURE

Pre-operative CT Scan Image Files.

Optional for those who had a previous CT scan for a prior traumatic event.

Intervention Type PROCEDURE

Eligibility Criteria

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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.

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.
Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role collaborator

Icahn School of Medicine at Mount Sinai

OTHER

Sponsor Role lead

Responsible Party

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Ethylin Wang Jabs

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Ethylin Wang Jabs, MD

Role: PRINCIPAL_INVESTIGATOR

Icahn School of Medicine at Mount Sinai

Inga Peter, PhD

Role: PRINCIPAL_INVESTIGATOR

Icahn School of Medicine at Mount Sinai

Locations

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The International Craniosynostosis Consortium at University of California at Davis

Davis, California, United States

Site Status

Yale University

Hartford, Connecticut, United States

Site Status

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, United States

Site Status

National Birth Defects Prevention Study at University of Iowa

Iowa City, Iowa, United States

Site Status

Johns Hopkins University

Baltimore, Maryland, United States

Site Status

Boston Children's Hospital

Boston, Massachusetts, United States

Site Status

Birth Defect Registries of New York State

Albany, New York, United States

Site Status

New York University

New York, New York, United States

Site Status

Icahn School of Medicine at Mount Sinai

New York, New York, United States

Site Status

Pennsylvania State Milton S. Hershey Medical Center

Hershey, Pennsylvania, United States

Site Status

Pennsylvania State University

University Park, Pennsylvania, United States

Site Status

Seton Family of Hospitals

Austin, Texas, United States

Site Status

Medical City Children's Hospital

Dallas, Texas, United States

Site Status

University of Texas at Southwestern

Dallas, Texas, United States

Site Status

University of Utah

Salt Lake City, Utah, United States

Site Status

University of Bordeaux

Talence, Aquitaine, France

Site Status

INSERM/ Hospital Necker-Enfants Malades

Paris, Cedex 14, France

Site Status

University Hospital Heidelberg

Heidelberg, , Germany

Site Status

Hospital Sant Joan de Deu

Barcelona, Esplugues de Llobregat, Spain

Site Status

Oxford University

Oxford, Oxfordshire, United Kingdom

Site Status

Countries

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United States France Germany Spain United Kingdom

References

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Heuze Y, Holmes G, Peter I, Richtsmeier JT, Jabs EW. Closing the Gap: Genetic and Genomic Continuum from Syndromic to Nonsyndromic Craniosynostoses. Curr Genet Med Rep. 2014 Sep 1;2(3):135-145. doi: 10.1007/s40142-014-0042-x.

Reference Type BACKGROUND
PMID: 26146596 (View on PubMed)

Heuze Y, Singh N, Basilico C, Jabs EW, Holmes G, Richtsmeier JT. Morphological comparison of the craniofacial phenotypes of mouse models expressing the Apert FGFR2 S252W mutation in neural crest- or mesoderm-derived tissues. Bone. 2014 Jun;63:101-9. doi: 10.1016/j.bone.2014.03.003. Epub 2014 Mar 13.

Reference Type BACKGROUND
PMID: 24632501 (View on PubMed)

Heuze Y, Martinez-Abadias N, Stella JM, Arnaud E, Collet C, Garcia Fructuoso G, Alamar M, Lo LJ, Boyadjiev SA, Di Rocco F, Richtsmeier JT. Quantification of facial skeletal shape variation in fibroblast growth factor receptor-related craniosynostosis syndromes. Birth Defects Res A Clin Mol Teratol. 2014 Apr;100(4):250-9. doi: 10.1002/bdra.23228. Epub 2014 Feb 27.

Reference Type BACKGROUND
PMID: 24578066 (View on PubMed)

Di Rocco F, Biosse Duplan M, Heuze Y, Kaci N, Komla-Ebri D, Munnich A, Mugniery E, Benoist-Lasselin C, Legeai-Mallet L. FGFR3 mutation causes abnormal membranous ossification in achondroplasia. Hum Mol Genet. 2014 Jun 1;23(11):2914-25. doi: 10.1093/hmg/ddu004. Epub 2014 Jan 12.

Reference Type BACKGROUND
PMID: 24419316 (View on PubMed)

Justice CM, Yagnik G, Kim Y, Peter I, Jabs EW, Erazo M, Ye X, Ainehsazan E, Shi L, Cunningham ML, Kimonis V, Roscioli T, Wall SA, Wilkie AO, Stoler J, Richtsmeier JT, Heuze Y, Sanchez-Lara PA, Buckley MF, Druschel CM, Mills JL, Caggana M, Romitti PA, Kay DM, Senders C, Taub PJ, Klein OD, Boggan J, Zwienenberg-Lee M, Naydenov C, Kim J, Wilson AF, Boyadjiev SA. A genome-wide association study identifies susceptibility loci for nonsyndromic sagittal craniosynostosis near BMP2 and within BBS9. Nat Genet. 2012 Dec;44(12):1360-4. doi: 10.1038/ng.2463. Epub 2012 Nov 18.

Reference Type BACKGROUND
PMID: 23160099 (View on PubMed)

Heuze Y, Martinez-Abadias N, Stella JM, Senders CW, Boyadjiev SA, Lo LJ, Richtsmeier JT. Unilateral and bilateral expression of a quantitative trait: asymmetry and symmetry in coronal craniosynostosis. J Exp Zool B Mol Dev Evol. 2012 Mar;318(2):109-22. doi: 10.1002/jezb.21449.

Reference Type BACKGROUND
PMID: 22532473 (View on PubMed)

Martinez-Abadias N, Heuze Y, Wang Y, Jabs EW, Aldridge K, Richtsmeier JT. FGF/FGFR signaling coordinates skull development by modulating magnitude of morphological integration: evidence from Apert syndrome mouse models. PLoS One. 2011;6(10):e26425. doi: 10.1371/journal.pone.0026425. Epub 2011 Oct 28.

Reference Type BACKGROUND
PMID: 22053191 (View on PubMed)

Heuze Y, Boyadjiev SA, Marsh JL, Kane AA, Cherkez E, Boggan JE, Richtsmeier JT. New insights into the relationship between suture closure and craniofacial dysmorphology in sagittal nonsyndromic craniosynostosis. J Anat. 2010 Aug;217(2):85-96. doi: 10.1111/j.1469-7580.2010.01258.x. Epub 2010 Jun 22.

Reference Type BACKGROUND
PMID: 20572900 (View on PubMed)

Wang Y, Sun M, Uhlhorn VL, Zhou X, Peter I, Martinez-Abadias N, Hill CA, Percival CJ, Richtsmeier JT, Huso DL, Jabs EW. Activation of p38 MAPK pathway in the skull abnormalities of Apert syndrome Fgfr2(+P253R) mice. BMC Dev Biol. 2010 Feb 22;10:22. doi: 10.1186/1471-213X-10-22.

Reference Type BACKGROUND
PMID: 20175913 (View on PubMed)

Percival CJ, Kawasaki K, Huang Y, Weiss KM, Jabs EW, Li R, Richtsmeier JT. Building Bones. Percival CJ, Richtsmeier JT, editors. Cambridge. Cambridge University Press; 2017. Chapter 2, The contribution of angiogenesis to variation in bone development and evolution; 26-51p.

Reference Type BACKGROUND

Kawasaki K, Richtsmeier JT. Building Bones. Percival CJ, Richtsmeier JT, editors. Cambridge. Cambridge University Press; 2017. Chapter 3, Association of the chondrocranium and dermatocranium in early skull development; 52-78p.

Reference Type BACKGROUND

Kawasaki K, Richtsmeier J. Building Bones. Percival CJ, Richtsmeier JT, editors. Cambridge. Cambridge University Press; 2017. Chapter Appendix, Appendix to Chapter 3 ; 303-315p.

Reference Type BACKGROUND

Singh N, Dutka T, Reeves RH, Richtsmeier JT. Chronic up-regulation of sonic hedgehog has little effect on postnatal craniofacial morphology of euploid and trisomic mice. Dev Dyn. 2016 Feb;245(2):114-22. doi: 10.1002/dvdy.24361. Epub 2015 Dec 6.

Reference Type BACKGROUND
PMID: 26509735 (View on PubMed)

Trainor PA, Richtsmeier JT. Facing up to the challenges of advancing Craniofacial Research. Am J Med Genet A. 2015 Jul;167(7):1451-4. doi: 10.1002/ajmg.a.37065. Epub 2015 Mar 28.

Reference Type BACKGROUND
PMID: 25820983 (View on PubMed)

Wilkie AOM, Johnson D, Wall SA. Clinical genetics of craniosynostosis. Curr Opin Pediatr. 2017 Dec;29(6):622-628. doi: 10.1097/MOP.0000000000000542.

Reference Type BACKGROUND
PMID: 28914635 (View on PubMed)

Richtsmeier JT, Jones MC, Lozanoff S, Trainor PA. The Society for Craniofacial Genetics and Developmental Biology 37th annual meeting. Am J Med Genet A. 2015 Jul;167(7):1455-73. doi: 10.1002/ajmg.a.37012. Epub 2015 Mar 30. No abstract available.

Reference Type BACKGROUND
PMID: 25820705 (View on PubMed)

Singh N, Dutka T, Devenney BM, Kawasaki K, Reeves RH, Richtsmeier JT. Acute upregulation of hedgehog signaling in mice causes differential effects on cranial morphology. Dis Model Mech. 2015 Mar;8(3):271-9. doi: 10.1242/dmm.017889. Epub 2014 Dec 24.

Reference Type BACKGROUND
PMID: 25540129 (View on PubMed)

Flaherty K, Singh N, Richtsmeier JT. Understanding craniosynostosis as a growth disorder. Wiley Interdiscip Rev Dev Biol. 2016 Jul;5(4):429-59. doi: 10.1002/wdev.227. Epub 2016 Mar 22.

Reference Type RESULT
PMID: 27002187 (View on PubMed)

Ye X, Guilmatre A, Reva B, Peter I, Heuze Y, Richtsmeier JT, Fox DJ, Goedken RJ, Jabs EW, Romitti PA. Mutation Screening of Candidate Genes in Patients with Nonsyndromic Sagittal Craniosynostosis. Plast Reconstr Surg. 2016 Mar;137(3):952-961. doi: 10.1097/01.prs.0000479978.75545.ee.

Reference Type RESULT
PMID: 26910679 (View on PubMed)

Musy M, Flaherty K, Raspopovic J, Robert-Moreno A, Richtsmeier JT, Sharpe J. A quantitative method for staging mouse embryos based on limb morphometry. Development. 2018 Apr 5;145(7):dev154856. doi: 10.1242/dev.154856.

Reference Type RESULT
PMID: 29540505 (View on PubMed)

Heuze Y, Kawasaki K, Schwarz T, Schoenebeck JJ, Richtsmeier JT. Developmental and Evolutionary Significance of the Zygomatic Bone. Anat Rec (Hoboken). 2016 Dec;299(12):1616-1630. doi: 10.1002/ar.23449.

Reference Type RESULT
PMID: 27870340 (View on PubMed)

Motch Perrine SM, Stecko T, Neuberger T, Jabs EW, Ryan TM, Richtsmeier JT. Integration of Brain and Skull in Prenatal Mouse Models of Apert and Crouzon Syndromes. Front Hum Neurosci. 2017 Jul 25;11:369. doi: 10.3389/fnhum.2017.00369. eCollection 2017.

Reference Type RESULT
PMID: 28790902 (View on PubMed)

Lee C, Richtsmeier JT, Kraft RH. A COMPUTATIONAL ANALYSIS OF BONE FORMATION IN THE CRANIAL VAULT USING A COUPLED REACTION-DIFFUSION-STRAIN MODEL. J Mech Med Biol. 2017 Jun;17(4):1750073. doi: 10.1142/S0219519417500737. Epub 2017 May 29.

Reference Type RESULT
PMID: 29225392 (View on PubMed)

Lesciotto KM, Heuze Y, Jabs EW, Bernstein JM, Richtsmeier JT. Choanal Atresia and Craniosynostosis: Development and Disease. Plast Reconstr Surg. 2018 Jan;141(1):156-168. doi: 10.1097/PRS.0000000000003928.

Reference Type RESULT
PMID: 29280877 (View on PubMed)

Motch Perrine SM, Wu M, Stephens NB, Kriti D, van Bakel H, Jabs EW, Richtsmeier JT. Mandibular dysmorphology due to abnormal embryonic osteogenesis in FGFR2-related craniosynostosis mice. Dis Model Mech. 2019 May 30;12(5):dmm038513. doi: 10.1242/dmm.038513.

Reference Type RESULT
PMID: 31064775 (View on PubMed)

Norwood JN, Zhang Q, Card D, Craine A, Ryan TM, Drew PJ. Anatomical basis and physiological role of cerebrospinal fluid transport through the murine cribriform plate. Elife. 2019 May 7;8:e44278. doi: 10.7554/eLife.44278.

Reference Type RESULT
PMID: 31063132 (View on PubMed)

Lee C, Richtsmeier JT, Kraft RH. A coupled reaction-diffusion-strain model predicts cranial vault formation in development and disease. Biomech Model Mechanobiol. 2019 Aug;18(4):1197-1211. doi: 10.1007/s10237-019-01139-z. Epub 2019 Apr 20.

Reference Type RESULT
PMID: 31006064 (View on PubMed)

Sewda A, White SR, Erazo M, Hao K, Garcia-Fructuoso G, Fernandez-Rodriguez I, Heuze Y, Richtsmeier JT, Romitti PA, Reva B, Jabs EW, Peter I. Nonsyndromic craniosynostosis: novel coding variants. Pediatr Res. 2019 Mar;85(4):463-468. doi: 10.1038/s41390-019-0274-2. Epub 2019 Jan 14.

Reference Type RESULT
PMID: 30651579 (View on PubMed)

Lesciotto KM, Richtsmeier JT. Craniofacial skeletal response to encephalization: How do we know what we think we know? Am J Phys Anthropol. 2019 Jan;168 Suppl 67(Suppl 67):27-46. doi: 10.1002/ajpa.23766.

Reference Type RESULT
PMID: 30680710 (View on PubMed)

Flaherty K, Richtsmeier JT. It's about Time: Ossification Center Formation in C57BL/6 Mice from E12(-)E16. J Dev Biol. 2018 Dec 15;6(4):31. doi: 10.3390/jdb6040031.

Reference Type RESULT
PMID: 30558321 (View on PubMed)

Holmes G, O'Rourke C, Motch Perrine SM, Lu N, van Bakel H, Richtsmeier JT, Jabs EW. Midface and upper airway dysgenesis in FGFR2-related craniosynostosis involves multiple tissue-specific and cell cycle effects. Development. 2018 Oct 5;145(19):dev166488. doi: 10.1242/dev.166488.

Reference Type RESULT
PMID: 30228104 (View on PubMed)

Martinez-Abadias N, Mateu Estivill R, Sastre Tomas J, Motch Perrine S, Yoon M, Robert-Moreno A, Swoger J, Russo L, Kawasaki K, Richtsmeier J, Sharpe J. Quantification of gene expression patterns to reveal the origins of abnormal morphogenesis. Elife. 2018 Sep 20;7:e36405. doi: 10.7554/eLife.36405.

Reference Type RESULT
PMID: 30234486 (View on PubMed)

Holmes G, Zhang L, Rivera J, Murphy R, Assouline C, Sullivan L, Oppeneer T, Jabs EW. C-type natriuretic peptide analog treatment of craniosynostosis in a Crouzon syndrome mouse model. PLoS One. 2018 Jul 26;13(7):e0201492. doi: 10.1371/journal.pone.0201492. eCollection 2018.

Reference Type RESULT
PMID: 30048539 (View on PubMed)

Richtsmeier JT. A century of development. Am J Phys Anthropol. 2018 Apr;165(4):726-740. doi: 10.1002/ajpa.23379. No abstract available.

Reference Type RESULT
PMID: 29574839 (View on PubMed)

Starbuck JM, Cole TM 3rd, Reeves RH, Richtsmeier JT. The Influence of trisomy 21 on facial form and variability. Am J Med Genet A. 2017 Nov;173(11):2861-2872. doi: 10.1002/ajmg.a.38464. Epub 2017 Sep 21.

Reference Type RESULT
PMID: 28941128 (View on PubMed)

Weiss K, Buchanan A, Richtsmeier J. How are we made?: Even well-controlled experiments show the complexity of our traits. Evol Anthropol. 2015 Jul-Aug;24(4):130-6. doi: 10.1002/evan.21454. No abstract available.

Reference Type RESULT
PMID: 26267434 (View on PubMed)

Lee C, Richtsmeier JT, Kraft RH. A computational analysis of bone formation in the cranial vault in the mouse. Front Bioeng Biotechnol. 2015 Mar 19;3:24. doi: 10.3389/fbioe.2015.00024. eCollection 2015.

Reference Type RESULT
PMID: 25853124 (View on PubMed)

Pitirri MK, Richtsmeier JT, Kawasaki M, Coupe AP, Perrine SM, Kawasaki K. Come together over me: Cells that form the dermatocranium and chondrocranium in mice. Anat Rec (Hoboken). 2025 Jul;308(7):1972-1993. doi: 10.1002/ar.25295. Epub 2023 Jul 27.

Reference Type RESULT
PMID: 37497849 (View on PubMed)

Lesciotto KM, Tomlinson L, Leonard S, Richtsmeier JT. Embryonic and early postnatal cranial bone volume and tissue mineral density values for C57BL/6J laboratory mice. Dev Dyn. 2022 Jul;251(7):1196-1208. doi: 10.1002/dvdy.458. Epub 2022 Feb 7.

Reference Type RESULT
PMID: 35092111 (View on PubMed)

Pitirri MK, Durham EL, Romano NA, Santos JI, Coupe AP, Zheng H, Chen DZ, Kawasaki K, Jabs EW, Richtsmeier JT, Wu M, Motch Perrine SM. Meckel's Cartilage in Mandibular Development and Dysmorphogenesis. Front Genet. 2022 May 16;13:871927. doi: 10.3389/fgene.2022.871927. eCollection 2022.

Reference Type RESULT
PMID: 35651944 (View on PubMed)

Wu M, Kriti D, van Bakel H, Jabs EW, Holmes G. Laser Capture Microdissection of Mouse Embryonic Cartilage and Bone for Gene Expression Analysis. J Vis Exp. 2019 Dec 18;(154). doi: 10.3791/60503.

Reference Type RESULT
PMID: 31904019 (View on PubMed)

Kawasaki K, Mikami M, Goto M, Shindo J, Amano M, Ishiyama M. The Evolution of Unusually Small Amelogenin Genes in Cetaceans; Pseudogenization, X-Y Gene Conversion, and Feeding Strategy. J Mol Evol. 2020 Mar;88(2):122-135. doi: 10.1007/s00239-019-09917-0. Epub 2019 Nov 22.

Reference Type RESULT
PMID: 31754761 (View on PubMed)

Pitirri MK, Kawasaki K, Richtsmeier JT. It takes two: Building the vertebrate skull from chondrocranium and dermatocranium. Vertebr Zool. 2020 Apr;70(4):587-600. Epub 2020 Oct 28.

Reference Type RESULT
PMID: 33163116 (View on PubMed)

Holmes G, Gonzalez-Reiche AS, Lu N, Zhou X, Rivera J, Kriti D, Sebra R, Williams AA, Donovan MJ, Potter SS, Pinto D, Zhang B, van Bakel H, Jabs EW. Integrated Transcriptome and Network Analysis Reveals Spatiotemporal Dynamics of Calvarial Suturogenesis. Cell Rep. 2020 Jul 7;32(1):107871. doi: 10.1016/j.celrep.2020.107871.

Reference Type RESULT
PMID: 32640236 (View on PubMed)

Lam AS, Liu CC, Deutsch GH, Rivera J, Perkins JA, Holmes G, Jabs EW, Cunningham ML, Dahl JP. Genotype-Phenotype Correlation of Tracheal Cartilaginous Sleeves and Fgfr2 Mutations in Mice. Laryngoscope. 2021 Apr;131(4):E1349-E1356. doi: 10.1002/lary.29060. Epub 2020 Sep 4.

Reference Type RESULT
PMID: 32886384 (View on PubMed)

Singh R, Cohen ASA, Poulton C, Hjortshoj TD, Akahira-Azuma M, Mendiratta G, Khan WA, Azmanov DN, Woodward KJ, Kirchhoff M, Shi L, Edelmann L, Baynam G, Scott SA, Jabs EW. Deletion of ERF and CIC causes abnormal skull morphology and global developmental delay. Cold Spring Harb Mol Case Stud. 2021 Jun 11;7(3):a005991. doi: 10.1101/mcs.a005991. Print 2021 Jun.

Reference Type RESULT
PMID: 34117072 (View on PubMed)

Holmes G, Gonzalez-Reiche AS, Saturne M, Motch Perrine SM, Zhou X, Borges AC, Shewale B, Richtsmeier JT, Zhang B, van Bakel H, Jabs EW. Single-cell analysis identifies a key role for Hhip in murine coronal suture development. Nat Commun. 2021 Dec 8;12(1):7132. doi: 10.1038/s41467-021-27402-5.

Reference Type RESULT
PMID: 34880220 (View on PubMed)

Nicoletti P, Zafer S, Matok L, Irron I, Patrick M, Haklai R, Evangelista JE, Marino GB, Ma'ayan A, Sewda A, Holmes G, Britton SR, Lee WJ, Wu M, Ru Y, Arnaud E, Botto L, Brody LC, Byren JC, Caggana M, Carmichael SL, Cilliers D, Conway K, Crawford K, Cuellar A, Di Rocco F, Engel M, Fearon J, Feldkamp ML, Finnell R, Fisher S, Freudlsperger C, Garcia-Fructuoso G, Hagge R, Heuze Y, Harshbarger RJ, Hobbs C, Howley M, Jenkins MM, Johnson D, Justice CM, Kane A, Kay D, Gosain AK, Langlois P, Legal-Mallet L, Lin AE, Mills JL, Morton JEV, Noons P, Olshan A, Persing J, Phipps JM, Redett R, Reefhuis J, Rizk E, Samson TD, Shaw GM, Sicko R, Smith N, Staffenberg D, Stoler J, Sweeney E, Taub PJ, Timberlake AT, Topczewska J, Wall SA, Wilson AF, Wilson LC, Boyadjiev SA, Wilkie AOM, Richtsmeier JT, Jabs EW, Romitti PA, Karasik D, Birnbaum RY, Peter I. Regulatory elements in SEM1-DLX5-DLX6 (7q21.3) locus contribute to genetic control of coronal nonsyndromic craniosynostosis and bone density-related traits. Genet Med Open. 2024;2:101851. doi: 10.1016/j.gimo.2024.101851. Epub 2024 May 17.

Reference Type RESULT
PMID: 39345948 (View on PubMed)

Lesciotto KM, Motch Perrine SM, Kawasaki M, Stecko T, Ryan TM, Kawasaki K, Richtsmeier JT. Phosphotungstic acid-enhanced microCT: Optimized protocols for embryonic and early postnatal mice. Dev Dyn. 2020 Apr;249(4):573-585. doi: 10.1002/dvdy.136. Epub 2019 Nov 28.

Reference Type RESULT
PMID: 31736206 (View on PubMed)

Lee C, Richtsmeier JT, Kraft RH. A MULTISCALE COMPUTATIONAL MODEL FOR THE GROWTH OF THE CRANIAL VAULT IN CRANIOSYNOSTOSIS. Int Mech Eng Congress Expo. 2014 Nov;2014:V009T12A061. doi: 10.1115/IMECE2014-38728.

Reference Type RESULT
PMID: 25909093 (View on PubMed)

Related Links

Access external resources that provide additional context or updates about the study.

http://limbstaging.crg.es/

The eMOSS staging system-free, public webtool for any PI requiring increased temporal resolution for research using embryonic mice. Developed thru a collaboration-Dr. Joan Richtsmeier lab, Penn State Univ \& Dr. James Sharpe lab, Center for G

Other Identifiers

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P01HD078233

Identifier Type: NIH

Identifier Source: secondary_id

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GCO 13-0147

Identifier Type: -

Identifier Source: org_study_id

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