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We sought to characterize the craniofacial phenotype of patients with the disease. Six patients with genetically confirmed JMC underwent comprehensive craniofacial phenotyping revealing a distinct facial appearance that prompted a cephalometric analysis demonstrating a pattern of mandibular retrognathia. Oral examination was notable for flat and shallow palate, delayed eruption pattern, and impacted maxillary teeth. Subclinical and\/or mild hearing loss was noted in 4 of 5 patients studied. The most common etiology was conductive, likely due to overcrowding of epitympanum which impedes the normal vibration of ossicles to sound. Paranasal sinus obliteration was noted in 5 of 6 patients. Computed tomography (CT) scan evaluation of craniofacial bones revealed bilaterally symmetric expansile lesions with predominant involvement of neural crest cell (NCC)-derived bones. Bilateral narrowing of facial nerve canals, particularly at the labyrinthine segment, was seen in 5 of 6 patients when compared to age-matched controls; 1 patient presented with progressive facial nerve palsy. Sagittal suture craniosynostosis was present in 5 of 6 patients\u2014one of whom had a history of cranial reconstruction for pansynostosis in infancy. All patients demonstrated a significant degree of upper airway stenosis, as well as a more anterior hyoid bone displacement. Two patients had a diagnosis of obstructive sleep apnea. 18F-NaF Positron-emission tomography (PET)-CT revealed increased uptake associated with the skull base and gnathic bones in all patients. In conclusion, this first detailed systematic evaluation of the craniofacial phenotype of patients with JMC demonstrates a distinct and pronounced phenotype that predominantly affects the NCC-derived cranial bones indicating a critical role of PTH1R signaling in their development. These affects can result in significant disease-related morbidity, include hearing loss, nerve compression, craniosynostosis, dentoskeletal malocclusion, and airway compromise; all of which require close monitoring.<\/jats:p>","DOI":"10.1093\/jbmrpl\/ziae156","type":"journal-article","created":{"date-parts":[[2024,11,26]],"date-time":"2024-11-26T12:39:07Z","timestamp":1732624747000},"source":"Crossref","is-referenced-by-count":2,"title":["Jansen metaphyseal chondrodysplasia: analysis of craniofacial manifestations"],"prefix":"10.1093","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-2652-9965","authenticated-orcid":false,"given":"Fiona","family":"Obiezu","sequence":"first","affiliation":[{"name":"Skeletal Disorders and Mineral Homeostasis Section, National Institute of Dental and Craniofacial Research, National Institutes of Health , Bethesda, MD 20892 ,","place":["United 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National Institutes of Health , , Bethesda, MD 20892 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Chu","sequence":"additional","affiliation":[{"name":"Department of Biomaterials and Regenerative Dentistry, University of Maryland School of Dentistry , Baltimore, MD 21201 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Golnar","family":"Jahanmir","sequence":"additional","affiliation":[{"name":"NIH Dental Clinic , , Bethesda, MD 20892 ,","place":["United States"]},{"name":"National Institute of Dental and Craniofacial Research, National Institutes of Health , , Bethesda, MD 20892 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0284-5299","authenticated-orcid":false,"given":"Kelly L","family":"Roszko","sequence":"additional","affiliation":[{"name":"Skeletal Disorders and Mineral Homeostasis Section, National Institute of Dental and Craniofacial Research, National Institutes of Health , Bethesda, MD 20892 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison","family":"Boyce","sequence":"additional","affiliation":[{"name":"Metabolic Bone Disorders Unit, National Institute of Dental and Craniofacial Research, National Institutes of Health , Bethesda, MD 20892 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faraz","family":"Farhadi","sequence":"additional","affiliation":[{"name":"Radiology and Imaging Sciences , , Bethesda, MD 20892 ,","place":["United States"]},{"name":"National Institutes of Health Clinical Center, National Institutes of Health , , Bethesda, MD 20892 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lee S","family":"Weinstein","sequence":"additional","affiliation":[{"name":"Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health , Bethesda, MD 20892 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel I","family":"Gafni","sequence":"additional","affiliation":[{"name":"Skeletal Disorders and Mineral Homeostasis Section, National Institute of Dental and Craniofacial Research, National Institutes of Health , Bethesda, MD 20892 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos R","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Skeletal Genomics Unit, National Human Genome Research Institute, National Institutes of Health , Bethesda, MD 20892 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harald","family":"J\u00fcppner","sequence":"additional","affiliation":[{"name":"Endocrine Unit, Massachusetts General Hospital and Harvard Medical School , Boston, MA 02114 ,","place":["United 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