{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T15:50:20Z","timestamp":1791561020200,"version":"4.3.4"},"reference-count":23,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T00:00:00Z","timestamp":1779753600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T00:00:00Z","timestamp":1779753600000},"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"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Achondroplasia (OMIM #100800), the most common skeletal dysplasia, results from the recurrent FGFR3 c.1138G\u2009&gt;\u2009A (p.Gly380Arg) gain\u2010of\u2010function variant, which constitutively activates fibroblast growth factor receptor 3 signaling and impairs endochondral ossification. The 16p11.2 microdeletion (OMIM #611913) is a recurrent ~600\u2009kb copy\u2010number variant associated with developmental delay, autism spectrum disorder, epilepsy, and obesity, encompassing dosage\u2010sensitive genes including MAPK3, KCTD13, and PRRT2. Recent genome\u2010wide analyses have linked 16p11.2 deletion to a 13.9\u2010fold increased risk of neuroblastoma, though no association with medulloblastoma has been documented. Medulloblastoma, the most common malignant pediatric brain tumor, is classified into molecularly defined subgroups\u2014WNT\u2010activated, SHH\u2010activated, Group 3, and Group 4\u2014each with distinct genetic drivers and clinical outcomes. We describe a 13\u2010year\u2010old male with achondroplasia confirmed by the pathogenic FGFR3 c.1138G\u2009&gt;\u2009A variant and a de novo 16p11.2 microdeletion who developed metastatic non\u2010WNT\/non\u2010SHH (Group 4) medulloblastoma with leptomeningeal dissemination (M3) at age 12. Despite multimodal therapy including resection, craniospinal irradiation, and combination chemotherapy, the tumor recurred and progressed. The patient died at age 13. To our knowledge, this is the first report of co\u2010occurring achondroplasia and 16p11.2 deletion complicated by medulloblastoma. Although neither condition independently confers established risk for this tumor, both perturb MAPK\/ERK signaling\u2014a pathway implicated in Group 4 medulloblastoma biology. This case underscores the importance of recognizing multilocus pathogenic variation and supports further investigation of potential interactions between developmental and oncogenic signaling networks.<\/jats:p>","DOI":"10.1002\/ajmg.a.70211","type":"journal-article","created":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T09:27:16Z","timestamp":1779787636000},"page":"2529-2536","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Co\u2010Occurrence of Achondroplasia and 16p11.2 Deletion Syndrome in a Child With Group 4 Medulloblastoma: Expanding the Spectrum of Dual Genetic Diagnoses"],"prefix":"10.1002","volume":"200","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0203-5261","authenticated-orcid":false,"given":"Hua","family":"Wang","sequence":"first","affiliation":[{"name":"Division of Genetics, Department of Pediatrics Loma Linda University School of Medicine, Loma Linda University Health  Loma Linda California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,26]]},"reference":[{"issue":"2","key":"e_1_2_12_2_1","first-page":"368","article-title":"Achondroplasia Is Defined by Recurrent G380R Mutations of FGFR3","volume":"56","author":"Bellus G. 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