{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T01:56:40Z","timestamp":1792202200200,"version":"4.4.0"},"reference-count":25,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,8,25]],"date-time":"2023-08-25T00:00:00Z","timestamp":1692921600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pediatr."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Spondylocostal dysostosis 4 (SCDO4) is characterized by short stature (mainly short trunk), dyspnea, brain meningocele, and spina bifida occulta, which is caused by homozygous or compound heterozygous <jats:italic>HES7<\/jats:italic> (HES family bHLH transcription factor 7) variants. The incidence of SCDO4 remains unknown due to the extremely low number of cases. This study reveals a novel homozygous <jats:italic>HES7<\/jats:italic> splicing variant causing SCDO4 and reviews all the previously reported <jats:italic>HES7<\/jats:italic> variants and corresponding symptoms, providing a comprehensive overview of the phenotypes and genotypes of <jats:italic>HES7<\/jats:italic> variants.<\/jats:p><\/jats:sec><jats:sec><jats:title>Case presentation<\/jats:title><jats:p>This case report focuses on a Chinese neonate who was first hospitalized for tachypnea, cleft palate, and short trunk. After a series of auxiliary examinations, the patient was also found to have deformities of vertebrae and rib, left hydronephrosis, and patent foramen ovale. He underwent surgery for congenital hydronephrosis at 5 months old and underwent cleft palate repair when he was 1 year old. After two and half years of follow-up, the boy developed normally. A novel homozygous <jats:italic>HES7 splicing<\/jats:italic> variant (c.226+1G&amp;gt;A, NM_001165967.2) was identified in the proband by whole-exome sequencing and verified by Sanger sequencing. The variant was inherited from both parents and minigene assays demonstrated that this variant resulted in the retention of intron3 in the <jats:italic>HES7<\/jats:italic> transcript. Including this case, a total of six <jats:italic>HES7<\/jats:italic> variants and 13 patients with SCDO4 have been reported.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our findings expand the genotype-phenotype knowledge of SCDO4 and provide new evidence for genetic counseling.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fped.2023.1201999","type":"journal-article","created":{"date-parts":[[2023,8,25]],"date-time":"2023-08-25T16:47:00Z","timestamp":1692982020000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["A novel homozygous HES7 splicing variant causing spondylocostal dysostosis 4: a case 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