{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T18:43:26Z","timestamp":1758307406545,"version":"3.44.0"},"reference-count":18,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T00:00:00Z","timestamp":1751414400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Investigation"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Importance<\/jats:title><jats:p>Cornelia de Lange syndrome (CdLS) is a rare genetic disorder characterized by a spectrum of developmental and physical anomalies. Understanding the clinical and genetic landscape of CdLS in pediatric patients is crucial for improving diagnosis and management.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To investigate the clinical and genetic characteristics of 19 pediatric patients with CdLS in China, with a focus on identifying the association between genetic variants and clinical severity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We performed whole exome sequencing on 19 patients with CdLS and compared their clinical characteristics based on the presence of null variants.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among the 19 patients, 16 (84.2%) showed global developmental delays and 14 (73.7%) experienced prenatal growth retardation and short stature. Craniofacial anomalies\u2013short noses and anteverted nares were observed in 94.7% (18\/19) of patients. Small hands and\/or feet were present in 16 patients, skin manifestations (hirsutism or mottled skin) in six, and hearing loss in four. Genetic testing identified 19 variants in <jats:italic>NIPBL<\/jats:italic> (78.9%, 15\/19), <jats:italic>SMC1A<\/jats:italic> (10.5%, 2\/19), and <jats:italic>RAD21<\/jats:italic> (10.5%, 2\/19), including 13 novel variants. <jats:italic>NIPBL<\/jats:italic> null variants correlated significantly with more severe growth impairments (<jats:italic>P<\/jats:italic> = 0.016) and microcephaly (<jats:italic>P<\/jats:italic> = 0.004). Although complete protein function loss often correlated with more severe clinical presentations, no significant difference in clinical scoring was observed (<jats:italic>P<\/jats:italic> = 0.600). Three patients treated with recombinant human growth hormone showed heterogeneous responses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>This study highlights the clinical heterogeneity of CdLS and suggests a potential link between specific genetic variants and disease severity. These findings warrant further research to optimize treatments and better understand the functional impact of these genetic variants.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ped4.70013","type":"journal-article","created":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T06:42:08Z","timestamp":1751438528000},"page":"293-299","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical and genetic characteristics of Cornelia de Lange syndrome in pediatric patients"],"prefix":"10.1002","volume":"9","author":[{"given":"Xiaoqiao","family":"Li","sequence":"first","affiliation":[{"name":"Department of Endocrinology, Genetics, Metabolism Beijing Children's Hospital Capital Medical University, National Center for Children's Health Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-1242-164X","authenticated-orcid":false,"given":"Ming","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Genetics, Metabolism Beijing Children's Hospital Capital Medical University, National Center for Children's Health Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Genetics, Metabolism Beijing Children's Hospital Capital Medical University, National Center for Children's Health Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenjing","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Genetics, Metabolism Beijing Children's Hospital Capital Medical University, National Center for Children's Health Beijing 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