{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T10:01:36Z","timestamp":1753869696073,"version":"3.41.2"},"reference-count":12,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,1,19]],"date-time":"2024-01-19T00:00:00Z","timestamp":1705622400000},"content-version":"vor","delay-in-days":18,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Epiphyseal, Vertebral, Ear, and Nose (EVEN)\u2010PLUS syndrome is a rare condition characterized by the involvement of the Epiphyses, Vertebrae, Ears, and Nose, plus other associated findings, due to pathogenic variants in the HSPA9 gene. Due to the sparse number of patients, the clinical phenotypic spectrum is not clear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We report two patients with pathogenic <jats:italic>HSPA9<\/jats:italic> variants from a Chinese family. Besides the core clinical features of EVEN\u2010PLUS syndrome, the two cases had seizures, developmental delay, and basal ganglia lesions in cerebral MRI. We also reviewed the previously published reports of patients with biallelic pathogenic <jats:italic>HSPA9<\/jats:italic> variants.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Together with the presented cases, 12 cases (9 females) were identified from 6 relevant research items for analysis. All patients had synophrys or arched eyebrows, hypoplastic or dysplastic ears, hypoplastic nasal bone, and dysplastic femoral head. Other specific craniofacial features (such as triangular nares), abnormal skeletal presentations (such as bifid femur, dysplastic epiphyses at the knee, dysplastic acetabula, delayed ossification, short stature, vertebral clefting, scoliosis, and dislocated patellae), congenital heart defects, and renal alterations are common clinical features. Two patients had seizures and basal ganglia lesions in cerebral MRI. Infrequent features, such as aplasia cutis, short thorax and sternum, and widely spaced nipples, are also observed in the syndrome. Thirteen variants associated with EVEN\u2010PLUS syndrome have been reported.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p><jats:italic>HSPA9<\/jats:italic> gene mutations should be suspected in all cases with specific craniofacial features, abnormal skeletal presentations, congenital heart defects, and renal alterations. Seizures and basal ganglia lesions are a new phenotype of EVEN\u2010PLUS syndrome.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.2335","type":"journal-article","created":{"date-parts":[[2024,1,19]],"date-time":"2024-01-19T12:28:48Z","timestamp":1705667328000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A new phenotype of <scp>EVEN\u2010PLUS<\/scp> syndrome in a Chinese family and literature review"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6617-4025","authenticated-orcid":false,"given":"Ming","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Neurology, Beijing Children's Hospital, Capital Medical University National Center for Children's Health  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huanhuan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology Baoding Children's Hospital  Baoding Hebei Province China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuhong","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Neurology Baoding Children's Hospital  Baoding Hebei Province China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Changhong","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Neurology, Beijing Children's Hospital, Capital Medical University National Center for Children's Health  Beijing China"},{"name":"Department of Neurology Baoding Children's Hospital  Baoding Hebei Province China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,1,19]]},"reference":[{"issue":"7","key":"e_1_2_14_2_1","first-page":"561","article-title":"Epiphyseal, vertebral, and ear (EVE) dysplasia: A new syndrome?","volume":"36","author":"Amiel J.","year":"1999","journal-title":"Journal of Medical Genetics"},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0117170"},{"key":"e_1_2_14_4_1","doi-asserted-by":"publisher","DOI":"10.4149\/av_2013_01_3"},{"key":"e_1_2_14_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.2039"},{"key":"e_1_2_14_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jpcb.9b00071"},{"key":"e_1_2_14_7_1","doi-asserted-by":"publisher","DOI":"10.4172\/1747\u20100862.1000350"},{"key":"e_1_2_14_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.62883"},{"key":"e_1_2_14_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580\u2010019\u20100133\u20103"},{"key":"e_1_2_14_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep17154"},{"key":"e_1_2_14_11_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102015\u201009\u2010659854"},{"key":"e_1_2_14_12_1","doi-asserted-by":"publisher","DOI":"10.4103\/1673\u20105374.346487"},{"key":"e_1_2_14_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.61808"}],"container-title":["Molecular Genetics &amp; Genomic Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.2335","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,29]],"date-time":"2024-01-29T12:26:15Z","timestamp":1706531175000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mgg3.2335"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1]]},"references-count":12,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,1]]}},"alternative-id":["10.1002\/mgg3.2335"],"URL":"https:\/\/doi.org\/10.1002\/mgg3.2335","archive":["Portico"],"relation":{},"ISSN":["2324-9269","2324-9269"],"issn-type":[{"type":"print","value":"2324-9269"},{"type":"electronic","value":"2324-9269"}],"subject":[],"published":{"date-parts":[[2024,1]]},"assertion":[{"value":"2023-06-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-11-28","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-01-19","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2335"}}