{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T05:20:04Z","timestamp":1788240004291,"version":"build-2803163510"},"reference-count":21,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T00:00:00Z","timestamp":1788134400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T00:00:00Z","timestamp":1788134400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    CHARGE syndrome (OMIM #214800) is an autosomal dominant disorder caused by mutations in the CHD7 gene in most cases. Although originally defined by the CHARGE acronym (coloboma, heart defects, choanal atresia, growth restriction, genital hypoplasia, and ear anomalies), the recognized phenotype has expanded considerably to include highly prevalent manifestations such as cranial nerve dysfunction, vestibular anomalies, feeding and gastrointestinal complications, endocrine abnormalities, and musculoskeletal involvement. Skeletal abnormalities have been described previously; however, the frequency, spectrum, and clinical significance of spinal abnormalities remain incompletely characterized and are likely underrecognized. We conducted a retrospective review of 54 individuals with CHARGE syndrome to characterize spinal involvement and evaluate implications for management. Skeletal imaging was available in 40 of the 54, among whom abnormalities demonstrated considerable phenotypic heterogeneity, highlighting the importance of systematic musculoskeletal evaluation. Skeletal abnormalities were identified in 70% of individuals and included vertebral segmentation defects, intervertebral disc space narrowing, rib anomalies, and scoliosis. Scoliosis or kyphosis of any degree was present in 60% of the imaged individuals. Cervical spine involvement was identified in 43%. Two individuals (4%) were found to have\n                    <jats:italic>os odontoideum<\/jats:italic>\n                    , one of whom developed clinically significant atlantoaxial instability requiring surgical stabilization. Osteopenia was identified in 33% of individuals. Our findings further support previous reports demonstrating that spinal abnormalities are common in CHARGE syndrome while identifying os odontoideum as a previously unrecognized cervical spine manifestation with important clinical implications. Given that neuroimaging is frequently performed in CHARGE syndrome for evaluation of inner ear and cranial nerve abnormalities, careful assessment of the cervical spine during these studies may facilitate early recognition of clinically significant abnormalities without substantially increasing imaging burden. Our findings also emphasize the importance of longitudinal orthopedic surveillance, proactive bone health management beginning in childhood, and multidisciplinary care incorporating rehabilitation strategies to optimize long\u2010term musculoskeletal outcomes.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.70279","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T05:05:37Z","timestamp":1788239137000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Spinal Involvement in Charge Syndrome: Implications for Management"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-3598-460X","authenticated-orcid":false,"given":"Adriana","family":"Gomes","sequence":"first","affiliation":[{"name":"University of California  San Diego California USA"},{"name":"Department of Pediatrics, Division of Developmental\u2010Behavioral Pediatrics Rady Children's Hospital San Diego  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-0746-1278","authenticated-orcid":false,"given":"\u00c1lvaro","family":"Mart\u00edn\u2010Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"University of California  San Diego California USA"},{"name":"Department of Pediatrics, Division of Dysmorphology\/Genetics Rady Children's Hospital San Diego  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-9015-7226","authenticated-orcid":false,"given":"Miguel","family":"del Campo Casanelles","sequence":"additional","affiliation":[{"name":"University of California  San Diego California USA"},{"name":"Department of Pediatrics, Division of Dysmorphology\/Genetics Rady Children's Hospital San Diego  San Diego California USA"},{"name":"\u00c0rea de Gen\u00e8tica Cl\u00ednica i Molecular Hospital Unversitari Vall D'hebron  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marilyn C.","family":"Jones","sequence":"additional","affiliation":[{"name":"University of California  San Diego California USA"},{"name":"Department of Pediatrics, Division of Dysmorphology\/Genetics Rady Children's Hospital San Diego  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7062-8843","authenticated-orcid":false,"given":"Daniela","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Head and Neck Surgery University of California  San Diego California USA"},{"name":"Division of Pediatric Otolaryngology Rady Children's Health  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4833-3747","authenticated-orcid":false,"given":"Lynne M.","family":"Bird","sequence":"additional","affiliation":[{"name":"University of California  San Diego California USA"},{"name":"Department of Pediatrics, Division of Dysmorphology\/Genetics Rady Children's Hospital San Diego  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,31]]},"reference":[{"issue":"5234","key":"e_1_2_11_2_1","doi-asserted-by":"crossref","first-page":"1212","DOI":"10.1136\/bmj.1.5234.1212","article-title":"Syndrome of Coloboma With Multiple Congenital Abnormalities in Infancy","volume":"1","author":"Angelman H.","year":"1961","journal-title":"British Medical Journal"},{"issue":"5","key":"e_1_2_11_3_1","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1136\/jmg.2010.087106","article-title":"CHD7 Mutations and CHARGE Syndrome: The Clinical Implications of an Expanding Phenotype","volume":"48","author":"Bergman J. E.","year":"2011","journal-title":"Journal of Medical Genetics"},{"issue":"3","key":"e_1_2_11_4_1","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1177\/000992289803700302","article-title":"CHARGE Association: An Update and Review for the Primary Pediatrician","volume":"37","author":"Blake K. D.","year":"1998","journal-title":"Clinical Pediatrics"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750\u20101172\u20101\u201034"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/adc.65.2.217"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13005\u2010020\u201000224\u20104Do"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.30564"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.31670"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.3174\/ajnr.A1380"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37435"},{"issue":"3","key":"e_1_2_11_12_1","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/S0022-3476(79)80513-2","article-title":"Choanal Atresia and Associated Multiple Anomalies","volume":"95","author":"Hall B. D.","year":"1979","journal-title":"Journal of Pediatrics"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37769Hi"},{"issue":"2","key":"e_1_2_11_14_1","doi-asserted-by":"crossref","first-page":"122","DOI":"10.3928\/0191-3913-19790301-10","article-title":"Colobomatous Microphthalmia, Heart Disease, Hearing Loss, and Mental Retardation: A Syndrome","volume":"16","author":"Hittner H. M.","year":"1979","journal-title":"Journal of Pediatric Ophthalmology and Strabismus"},{"issue":"4","key":"e_1_2_11_15_1","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1136\/jmg.2005.036061","article-title":"CHARGE Syndrome: The Phenotypic Spectrum of Mutations in the CHD7 Gene","volume":"43","author":"Jongmans M. C.","year":"2006","journal-title":"Journal of Medical Genetics"},{"key":"e_1_2_11_16_1","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1002\/ajmg.c.31591","article-title":"Phenotype and Genotype Analysis of a French Cohort of 119 Patients With CHARGE Syndrome","volume":"175","author":"Legendre M.","year":"2017","journal-title":"American Journal of Medical Genetics Part C: Seminars in Medical Genetics"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.3174\/ajnr.A5"},{"issue":"2","key":"e_1_2_11_18_1","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/S0022-3476(81)80454-4","article-title":"Coloboma, Congenital Heart Disease, and Choanal Atresia With Multiple Anomalies: CHARGE Association","volume":"99","author":"Pagon R. A.","year":"1981","journal-title":"Journal of Pediatrics"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0031650"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.38085"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.31592"},{"issue":"3","key":"e_1_2_11_22_1","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1002\/ajmg.a.30559","article-title":"Updated Diagnostic Criteria for CHARGE Syndrome: A Proposal","volume":"133","author":"Verloes A.","year":"2005","journal-title":"American Journal of Medical Genetics Part A"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.70279","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ajmg.a.70279","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.70279","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T05:05:40Z","timestamp":1788239140000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.70279"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,31]]},"references-count":21,"alternative-id":["10.1002\/ajmg.a.70279"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.70279","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,31]]},"assertion":[{"value":"2026-05-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-05","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-31","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"ajmg.a.70279"}}