<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03025763</url>
  </required_header>
  <id_info>
    <org_study_id>GCO 13-0147</org_study_id>
    <secondary_id>P01HD078233</secondary_id>
    <nct_id>NCT03025763</nct_id>
  </id_info>
  <brief_title>Network Of Clinical Research Studies On Craniosynostosis, Skull Malformations With Premature Fusion Of Skull Bones</brief_title>
  <official_title>Craniosynostosis Network</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Icahn School of Medicine at Mount Sinai</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Icahn School of Medicine at Mount Sinai</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Craniosynostosis (CS) is a common malformation occurring in ~4 per 10,000 live births in&#xD;
      which the sutures between skull bones close too early, causing long-term problems with brain&#xD;
      and skull growth. Infants with CS typically require extensive surgical treatment and may&#xD;
      experience many perioperative complications, including hemorrhage and re-synostosis. Even&#xD;
      with successful surgery, children can experience developmental and learning disabilities or&#xD;
      vision problems. Most often, CS appears as isolated nonsyndromic CS (NSC). Of the several&#xD;
      subtypes of CS, unilateral or bilateral fusion of the coronal suture is the second most&#xD;
      common form of CS accounting for 20-30% of all NSC cases. The etiology of coronal NSC (cNSC)&#xD;
      is not well understood, although the published literature suggests that it is a&#xD;
      multifactorial condition. About 5-14% of coronal craniosynostosis patients have a positive&#xD;
      family history, with a specific genetic etiology identified in &gt;25% of cNSC cases, suggesting&#xD;
      a strong genetic component in the pathogenesis of this birth defect. The causes for cNSC and&#xD;
      its phenotypic heterogeneity remain largely unknown. An international team of investigators&#xD;
      will generate large genomic and gene expression datasets on samples from patients with cNSC.&#xD;
      State-of-the-art imaging, genetic, and developmental and systems biology approaches will be&#xD;
      used to quantitatively model novel pathways and networks involved in the development of cNSC.&#xD;
      Novel variant-, gene- and network-level analyses will be performed on the genomic data&#xD;
      obtained from cNSC cases, their relatives, and controls to identify novel variants and&#xD;
      genetic regions associated with cNCS. Quantitative, analytical, and functional validations of&#xD;
      these predictions will provide insights into the etiology and possible therapeutic targets&#xD;
      for CS and potentially other bone-related disorders.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The long-term goal of the Program Project, Craniosynostosis Network, is to elucidate normal&#xD;
      and abnormal craniofacial biology to ultimately improve the treatment of craniofacial&#xD;
      disorders. Craniosynostosis and other skull abnormalities are among the most common human&#xD;
      malformations usually requiring surgical and medical intervention. The Network will integrate&#xD;
      three projects and two cores. Scientists with diverse expertise including anthropology,&#xD;
      morphometry, imaging, birth defects, developmental biology, genetics, genomics, epidemiology,&#xD;
      statistics, and systems biology will explore the determinants of the fate of the relevant&#xD;
      mesenchymal progenitor cells, abnormalities in osteogenesis that contribute to global skull&#xD;
      growth abnormality and premature closure of cranial sutures, especially the coronal suture.&#xD;
      High quality genomic data will be obtained from patients with coronal nonsyndromic&#xD;
      craniosynostosis (cNSC) and their available parents. Novel genome-wide variant-, gene- and&#xD;
      network-level analyses will be performed on these families to identify novel variants and&#xD;
      genetic regions associated with coronal craniosynostosis.&#xD;
&#xD;
      This study is a multi-center, open-enrollment, retrospective study, employing both&#xD;
      family-based and case-control study designs.&#xD;
&#xD;
      Approximately 4000 cNSC patients, their family members, and controls will be recruited by&#xD;
      Icahn School of Medicine at Mount Sinai and the majority will be recruited from the more than&#xD;
      10 collaborating institutions worldwide.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">January 13, 2015</start_date>
  <completion_date type="Anticipated">January 31, 2028</completion_date>
  <primary_completion_date type="Anticipated">January 31, 2028</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Other</observational_model>
    <time_perspective>Other</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Phenotype-genotype gene expression correlations</measure>
    <time_frame>up to 5 years</time_frame>
    <description>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.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of gene mutations</measure>
    <time_frame>up to 5 years</time_frame>
    <description>gene mutations and variants may be found that are significantly associated with coronal nonsyndromic craniosynostosis</description>
  </secondary_outcome>
  <number_of_groups>3</number_of_groups>
  <enrollment type="Actual">2145</enrollment>
  <condition>Craniosynostosis</condition>
  <arm_group>
    <arm_group_label>Coronal Nonsyndromic Craniosynostosis, trios</arm_group_label>
    <description>Participants with diagnosis of coronal, nonsyndromic craniosynostosis including affected and unaffected biological parents</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Coronal, nonsyndromic craniosynostosis</arm_group_label>
    <description>Participants with coronal, nonsyndromic craniosynostosis when biological parents are not available</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Unaffected controls</arm_group_label>
    <description>Unaffected controls who may have undergone clinically indicated craniofacial surgery for trauma or conditions other than craniosynostosis or bone disease</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Craniosynostosis Network Environmental Survey</intervention_name>
    <description>Questionnaire is administered to the mothers of affected participants regarding medical history and environmental exposures during pregnancy, delivery, and neonatal period. Optional.</description>
    <arm_group_label>Coronal Nonsyndromic Craniosynostosis, trios</arm_group_label>
    <arm_group_label>Coronal, nonsyndromic craniosynostosis</arm_group_label>
    <arm_group_label>Unaffected controls</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>2D/3D Photography</intervention_name>
    <description>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.</description>
    <arm_group_label>Coronal Nonsyndromic Craniosynostosis, trios</arm_group_label>
    <arm_group_label>Coronal, nonsyndromic craniosynostosis</arm_group_label>
    <arm_group_label>Unaffected controls</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Buccal Swab Cell Sampling</intervention_name>
    <description>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.</description>
    <arm_group_label>Coronal Nonsyndromic Craniosynostosis, trios</arm_group_label>
    <arm_group_label>Coronal, nonsyndromic craniosynostosis</arm_group_label>
    <arm_group_label>Unaffected controls</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Blood sampling</intervention_name>
    <description>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.</description>
    <arm_group_label>Coronal Nonsyndromic Craniosynostosis, trios</arm_group_label>
    <arm_group_label>Coronal, nonsyndromic craniosynostosis</arm_group_label>
    <arm_group_label>Unaffected controls</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Skin Biopsy</intervention_name>
    <description>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.</description>
    <arm_group_label>Coronal Nonsyndromic Craniosynostosis, trios</arm_group_label>
    <arm_group_label>Coronal, nonsyndromic craniosynostosis</arm_group_label>
    <arm_group_label>Unaffected controls</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Tissues from a Clinically Indicated Procedure</intervention_name>
    <description>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.</description>
    <arm_group_label>Coronal Nonsyndromic Craniosynostosis, trios</arm_group_label>
    <arm_group_label>Coronal, nonsyndromic craniosynostosis</arm_group_label>
    <arm_group_label>Unaffected controls</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Pre-operative CT Scan Image Files.</intervention_name>
    <description>Optional for those who had a previous CT scan for a prior traumatic event.</description>
    <arm_group_label>Coronal Nonsyndromic Craniosynostosis, trios</arm_group_label>
    <arm_group_label>Coronal, nonsyndromic craniosynostosis</arm_group_label>
    <arm_group_label>Unaffected controls</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Saliva, blood, white blood cells, DNA, RNA, and generated induced pluripotent stem cells&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Individuals with coronal nonsyndromic craniosynostosis (cNSC) and their relatives and&#xD;
        controls (including noncraniosynostosis patients having neurosurgery for another surgical&#xD;
        indication) will be included in this study. Approximately 4,000 individuals will&#xD;
        participate of either gender and all ages, ethnicities, and race. All research subjects&#xD;
        will be consented through approved IRB protocols at Icahn School of Medicine at Mount Sinai&#xD;
        or respective collaborating institutions which will be governed by their own institutional&#xD;
        IRB committees. Only de-identified medical information, CT scans, and samples from&#xD;
        collaborating institutions will be shared with Mount Sinai.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Cases with diagnosis of coronal&#xD;
&#xD;
          -  Unaffected relatives of cases&#xD;
&#xD;
          -  Unaffected controls including those who may have undergone clinically indicated&#xD;
             craniofacial surgery for trauma or conditions other than craniosynostosis or bone&#xD;
             disease. These individuals will be recruited at some of the other collaborating&#xD;
             institutions, but not at Mount Sinai.&#xD;
&#xD;
        Individuals of any racial or ethnic group with the established or suspected clinical&#xD;
        diagnosis of coronal, nonsyndromic craniosynostosis will be included in this study.&#xD;
        Unaffected relatives, such as their biological parents and/or sibs, will also be included&#xD;
        to contribute medical information and samples as negative controls for our study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Those who fit the criteria, but who choose not to participate&#xD;
&#xD;
          -  Those who do not meet the criteria.&#xD;
&#xD;
          -  Other than children, no vulnerable individuals will be recruited, such as intellectual&#xD;
             impaired individuals or prisoners.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ethylin Wang Jabs, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Icahn School of Medicine at Mount Sinai</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Inga Peter, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Icahn School of Medicine at Mount Sinai</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>The International Craniosynostosis Consortium at University of California at Davis</name>
      <address>
        <city>Davis</city>
        <state>California</state>
        <zip>95616</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Yale University</name>
      <address>
        <city>Hartford</city>
        <state>Connecticut</state>
        <zip>06520</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ann &amp; Robert H. Lurie Children's Hospital of Chicago</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Birth Defects Prevention Study at University of Iowa</name>
      <address>
        <city>Iowa City</city>
        <state>Iowa</state>
        <zip>52242</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Johns Hopkins University</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21218</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Boston Children's Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Birth Defect Registries of New York State</name>
      <address>
        <city>Albany</city>
        <state>New York</state>
        <zip>12237</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>New York University</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10016</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Icahn School of Medicine at Mount Sinai</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10029</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pennsylvania State Milton S. Hershey Medical Center</name>
      <address>
        <city>Hershey</city>
        <state>Pennsylvania</state>
        <zip>17033</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pennsylvania State University</name>
      <address>
        <city>University Park</city>
        <state>Pennsylvania</state>
        <zip>16802</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Seton Family of Hospitals</name>
      <address>
        <city>Austin</city>
        <state>Texas</state>
        <zip>78723</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical City Children's Hospital</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75230</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Texas at Southwestern</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75390</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Utah</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84158</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Bordeaux</name>
      <address>
        <city>Talence</city>
        <state>Aquitaine</state>
        <zip>33405</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>INSERM/ Hospital Necker-Enfants Malades</name>
      <address>
        <city>Paris</city>
        <state>Cedex 14</state>
        <zip>75993</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital Heidelberg</name>
      <address>
        <city>Heidelberg</city>
        <zip>69120</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Sant Joan de Deu</name>
      <address>
        <city>Barcelona</city>
        <state>Esplugues De Llobregat</state>
        <zip>08950</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oxford University</name>
      <address>
        <city>Oxford</city>
        <state>Oxfordshire</state>
        <zip>OX1 2JD</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
    <country>Germany</country>
    <country>Spain</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://labs.icahn.mssm.edu/peterlab/craniosynostosis-network/</url>
    <description>Information about craniosynostosis and the Craniosynostosis Network Project</description>
  </link>
  <link>
    <url>http://limbstaging.crg.es/</url>
    <description>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 &amp; Dr. James Sharpe lab, Center for G</description>
  </link>
  <reference>
    <citation>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.</citation>
    <PMID>26146596</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>24632501</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>24578066</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>24419316</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>23160099</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>22532473</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>22053191</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>20572900</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>20175913</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
  </reference>
  <reference>
    <citation>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.</citation>
  </reference>
  <reference>
    <citation>Kawasaki K, Richtsmeier J. Building Bones. Percival CJ, Richtsmeier JT, editors. Cambridge. Cambridge University Press; 2017. Chapter Appendix, Appendix to Chapter 3 ; 303-315p.</citation>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>26509735</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>25820983</PMID>
  </reference>
  <results_reference>
    <citation>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.</citation>
    <PMID>27002187</PMID>
  </results_reference>
  <results_reference>
    <citation>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.</citation>
    <PMID>26910679</PMID>
  </results_reference>
  <results_reference>
    <citation>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.</citation>
    <PMID>29540505</PMID>
  </results_reference>
  <results_reference>
    <citation>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.</citation>
    <PMID>27870340</PMID>
  </results_reference>
  <results_reference>
    <citation>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.</citation>
    <PMID>28790902</PMID>
  </results_reference>
  <results_reference>
    <citation>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.</citation>
    <PMID>29225392</PMID>
  </results_reference>
  <results_reference>
    <citation>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.</citation>
    <PMID>29280877</PMID>
  </results_reference>
  <results_reference>
    <citation>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.</citation>
    <PMID>31064775</PMID>
  </results_reference>
  <results_reference>
    <citation>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.</citation>
    <PMID>31063132</PMID>
  </results_reference>
  <results_reference>
    <citation>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.</citation>
    <PMID>31006064</PMID>
  </results_reference>
  <results_reference>
    <citation>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.</citation>
    <PMID>30651579</PMID>
  </results_reference>
  <results_reference>
    <citation>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.</citation>
    <PMID>30680710</PMID>
  </results_reference>
  <results_reference>
    <citation>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.</citation>
    <PMID>30558321</PMID>
  </results_reference>
  <results_reference>
    <citation>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.</citation>
    <PMID>30228104</PMID>
  </results_reference>
  <results_reference>
    <citation>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.</citation>
    <PMID>30234486</PMID>
  </results_reference>
  <results_reference>
    <citation>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.</citation>
    <PMID>30048539</PMID>
  </results_reference>
  <results_reference>
    <citation>Richtsmeier JT. A century of development. Am J Phys Anthropol. 2018 Apr;165(4):726-740. doi: 10.1002/ajpa.23379. No abstract available.</citation>
    <PMID>29574839</PMID>
  </results_reference>
  <results_reference>
    <citation>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.</citation>
    <PMID>28941128</PMID>
  </results_reference>
  <results_reference>
    <citation>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.</citation>
    <PMID>26267434</PMID>
  </results_reference>
  <results_reference>
    <citation>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.</citation>
    <PMID>25853124</PMID>
  </results_reference>
  <results_reference>
    <citation>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). 2023 Jul 27. doi: 10.1002/ar.25295. Online ahead of print.</citation>
    <PMID>37497849</PMID>
  </results_reference>
  <results_reference>
    <citation>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.</citation>
    <PMID>35092111</PMID>
  </results_reference>
  <results_reference>
    <citation>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.</citation>
    <PMID>35651944</PMID>
  </results_reference>
  <results_reference>
    <citation>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.</citation>
    <PMID>31904019</PMID>
  </results_reference>
  <results_reference>
    <citation>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.</citation>
    <PMID>31754761</PMID>
  </results_reference>
  <results_reference>
    <citation>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.</citation>
    <PMID>33163116</PMID>
  </results_reference>
  <results_reference>
    <citation>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.</citation>
    <PMID>32640236</PMID>
  </results_reference>
  <results_reference>
    <citation>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.</citation>
    <PMID>32886384</PMID>
  </results_reference>
  <results_reference>
    <citation>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.</citation>
    <PMID>34117072</PMID>
  </results_reference>
  <results_reference>
    <citation>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.</citation>
    <PMID>34880220</PMID>
  </results_reference>
  <verification_date>September 2023</verification_date>
  <study_first_submitted>January 17, 2017</study_first_submitted>
  <study_first_submitted_qc>January 17, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 20, 2017</study_first_posted>
  <last_update_submitted>September 5, 2023</last_update_submitted>
  <last_update_submitted_qc>September 5, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 8, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Icahn School of Medicine at Mount Sinai</investigator_affiliation>
    <investigator_full_name>Ethylin Wang Jabs</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>Craniosynostosis</keyword>
  <keyword>Bone</keyword>
  <keyword>Birth Defect</keyword>
  <keyword>Congenital Anomaly</keyword>
  <keyword>Malformation</keyword>
  <keyword>Genetics</keyword>
  <keyword>Genomics</keyword>
  <keyword>Skull</keyword>
  <keyword>Human</keyword>
  <keyword>Mouse</keyword>
  <keyword>Imaging</keyword>
  <keyword>Cell Biology</keyword>
  <keyword>Induced Pluripotent Stem Cells</keyword>
  <keyword>System Biology</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Craniosynostoses</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Clinical results from chromosomal analysis and DNA mutation analysis performed in CLIA approved laboratories with standard clinical genetic counseling will be given to the patient upon request. Individual research results will be made available to the individual from the PI or their primary care physician (PCP) who has obtained preliminary results from the PI from our non-CLIA laboratory, as long as the PCP can confirm and validate the lab results through a CLIA approved lab before the results are given to the subjects.</ipd_description>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03025763
org study id: GCO 13-0147
secondary id: P01HD078233
nct id: NCT03025763
lead sponsor: 
collaborator: 
has dmc: No
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.
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.
observational model: Other
time perspective: Other
measure: Phenotype-genotype gene expression correlations
time frame: up to 5 years
description: 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.
measure: Incidence of gene mutations
time frame: up to 5 years
description: gene mutations and variants may be found that are significantly associated with coronal nonsyndromic craniosynostosis
arm group label: Coronal Nonsyndromic Craniosynostosis, trios
description: Participants with diagnosis of coronal, nonsyndromic craniosynostosis including affected and unaffected biological parents
arm group label: Coronal, nonsyndromic craniosynostosis
description: Participants with coronal, nonsyndromic craniosynostosis when biological parents are not available
arm group label: Unaffected controls
description: Unaffected controls who may have undergone clinically indicated craniofacial surgery for trauma or conditions other than craniosynostosis or bone disease
intervention type: Other
intervention name: Craniosynostosis Network Environmental Survey
description: Questionnaire is administered to the mothers of affected participants regarding medical history and environmental exposures during pregnancy, delivery, and neonatal period. Optional.
arm group label: Coronal Nonsyndromic Craniosynostosis, trios
arm group label: Coronal, nonsyndromic craniosynostosis
arm group label: Unaffected controls
intervention type: Other
intervention name: 2D/3D Photography
description: 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.
arm group label: Coronal Nonsyndromic Craniosynostosis, trios
arm group label: Coronal, nonsyndromic craniosynostosis
arm group label: Unaffected controls
intervention type: Procedure
intervention name: Buccal Swab Cell Sampling
description: 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.
arm group label: Coronal Nonsyndromic Craniosynostosis, trios
arm group label: Coronal, nonsyndromic craniosynostosis
arm group label: Unaffected controls
intervention type: Procedure
intervention name: Blood sampling
description: 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.
arm group label: Coronal Nonsyndromic Craniosynostosis, trios
arm group label: Coronal, nonsyndromic craniosynostosis
arm group label: Unaffected controls
intervention type: Procedure
intervention name: Skin Biopsy
description: 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.
arm group label: Coronal Nonsyndromic Craniosynostosis, trios
arm group label: Coronal, nonsyndromic craniosynostosis
arm group label: Unaffected controls
intervention type: Procedure
intervention name: Tissues from a Clinically Indicated Procedure
description: 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.
arm group label: Coronal Nonsyndromic Craniosynostosis, trios
arm group label: Coronal, nonsyndromic craniosynostosis
arm group label: Unaffected controls
intervention type: Procedure
intervention name: Pre-operative CT Scan Image Files.
description: Optional for those who had a previous CT scan for a prior traumatic event.
arm group label: Coronal Nonsyndromic Craniosynostosis, trios
arm group label: Coronal, nonsyndromic craniosynostosis
arm group label: Unaffected controls
Saliva, blood, white blood cells, DNA, RNA, and generated induced pluripotent stem cells
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: 80 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Ethylin Wang Jabs, MD
role: Principal Investigator
affiliation: Icahn School of Medicine at Mount Sinai
last name: Inga Peter, PhD
role: Principal Investigator
affiliation: Icahn School of Medicine at Mount Sinai
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: France
country: Germany
country: Spain
country: United Kingdom
country: United States
url: http://labs.icahn.mssm.edu/peterlab/craniosynostosis-network/
description: Information about craniosynostosis and the Craniosynostosis Network Project
url: http://limbstaging.crg.es/
description: 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
citation: 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.
PMID: 26146596
citation: 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.
PMID: 24632501
citation: 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.
PMID: 24578066
citation: 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.
PMID: 24419316
citation: 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.
PMID: 23160099
citation: 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.
PMID: 22532473
citation: 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.
PMID: 22053191
citation: 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.
PMID: 20572900
citation: 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.
PMID: 20175913
citation: 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.
citation: 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.
citation: Kawasaki K, Richtsmeier J. Building Bones. Percival CJ, Richtsmeier JT, editors. Cambridge. Cambridge University Press; 2017. Chapter Appendix, Appendix to Chapter 3 ; 303-315p.
citation: 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.
PMID: 26509735
citation: 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.
PMID: 25820983
citation: 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.
PMID: 27002187
citation: 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.
PMID: 26910679
citation: 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.
PMID: 29540505
citation: 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.
PMID: 27870340
citation: 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.
PMID: 28790902
citation: 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.
PMID: 29225392
citation: 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.
PMID: 29280877
citation: 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.
PMID: 31064775
citation: 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.
PMID: 31063132
citation: 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.
PMID: 31006064
citation: 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.
PMID: 30651579
citation: 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.
PMID: 30680710
citation: 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.
PMID: 30558321
citation: 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.
PMID: 30228104
citation: 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.
PMID: 30234486
citation: 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.
PMID: 30048539
citation: Richtsmeier JT. A century of development. Am J Phys Anthropol. 2018 Apr;165(4):726-740. doi: 10.1002/ajpa.23379. No abstract available.
PMID: 29574839
citation: 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.
PMID: 28941128
citation: 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.
PMID: 26267434
citation: 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.
PMID: 25853124
citation: 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). 2023 Jul 27. doi: 10.1002/ar.25295. Online ahead of print.
PMID: 37497849
citation: 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.
PMID: 35092111
citation: 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.
PMID: 35651944
citation: 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.
PMID: 31904019
citation: 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.
PMID: 31754761
citation: 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.
PMID: 33163116
citation: 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.
PMID: 32640236
citation: 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.
PMID: 32886384
citation: 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.
PMID: 34117072
citation: 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.
PMID: 34880220
responsible party type: Principal Investigator
investigator affiliation: Icahn School of Medicine at Mount Sinai
investigator full name: Ethylin Wang Jabs
investigator title: Professor
mesh term: Craniosynostoses
sharing ipd: Yes
ipd description: Clinical results from chromosomal analysis and DNA mutation analysis performed in CLIA approved laboratories with standard clinical genetic counseling will be given to the patient upon request. Individual research results will be made available to the individual from the PI or their primary care physician (PCP) who has obtained preliminary results from the PI from our non-CLIA laboratory, as long as the PCP can confirm and validate the lab results through a CLIA approved lab before the results are given to the subjects.