{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T15:59:18Z","timestamp":1753891158601,"version":"3.41.2"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,11,29]],"date-time":"2022-11-29T00:00:00Z","timestamp":1669680000000},"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. Genet."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> Fetal bradycardia is a common but severe condition. In addition to autoimmune-mediated fetal heart block, several types of channelopathies induce high-degree atrioventricular block (AVB). Long QT syndrome (LQTS) is a major cause of non-autoimmune-mediated fetal heart block. Due to the limitations of prenatal diagnostic technologies, LQTS is seldom identified unless fetal genetic screening is performed. Thus, long-term prenatal dexamethasone (DEX) exposure can become a challenge for these patients. We report on a rare case of a novel <jats:italic>KCNH2<\/jats:italic> variant related to LQTS and associated with high-degree fetal AVB with long-term DEX exposure. This case led us to review our prenatal administration strategy for such patients.<\/jats:p><jats:p><jats:bold>Case Presentation:<\/jats:bold> A fetus was identified with high-degree AVB (2:1 transduction at 28 + 2 gestational weeks). Typical tests of immune function in the pregnant woman were conducted including tests for thyroid function, rheumatic screening, autoimmune antibodies (such as anti-Ro\/SSA and anti-La\/SSB), and anti-nuclear antibodies (anti-ANA). Following the recommended protocol, the pregnant patient received DEX (0.75\u00a0mg\/day) during pregnancy. Subsequently, the fetal AVB changed from 2:1 to prolonged AV intervals with ventricular tachycardia, which suggested a therapeutic benefit of DEX in some respects. However, a high-degree AVB with a significantly prolonged QTc interval was identified in the neonate following birth. Genetic testing revealed that a <jats:italic>KCNH2<\/jats:italic> c.1868C&amp;gt;A variant induced LQTS. The body length remained approximately -3.2 SD from the reference value after prenatal long-term DEX exposure, which indicated a developmental restriction. Additionally, the functional validation experiments were performed to demonstrate the prolonged duration of calcium transit both in depolarization and repolarization with the <jats:italic>KCNH2<\/jats:italic> c.1868C&amp;gt;A variant.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> Genetic screening should be recommended in fetuses with autoimmune antibody negative high-degree AVB, especially for 2:1 transduction AVB and in fetuses with changes in fetal heart rhythm following initial DEX treatment. Genetic screening may help identify genetic variant\u2013related channelopathies and avoid unexpected prenatal exposure of DEX and its possible long-term adverse postnatal complications.<\/jats:p>","DOI":"10.3389\/fgene.2022.1010078","type":"journal-article","created":{"date-parts":[[2022,11,29]],"date-time":"2022-11-29T06:46:56Z","timestamp":1669704416000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Case Report: A novel KNCH2 variant-induced fetal heart block and the advantages of fetal genomic sequencing in prenatal long-term dexamethasone exposure"],"prefix":"10.3389","volume":"13","author":[{"given":"Huiping","family":"Huang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siyuan","family":"Jing","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shaoying","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Wei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qian","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yimin","family":"Hua","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yifei","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haiyan","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaiyu","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,11,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"418","DOI":"10.1161\/circulationaha.119.043132","article-title":"An international, multicentered, evidence-based reappraisal of genes reported to cause congenital long QT syndrome","volume":"141","author":"Adler","year":"2020","journal-title":"Circulation"},{"key":"B2","doi-asserted-by":"publisher","first-page":"781","DOI":"10.1016\/j.hrthm.2010.02.035","article-title":"Congenital long QT syndrome and 2:1 atrioventricular block: An optimistic outcome in the current era","volume":"7","author":"Aziz","year":"2010","journal-title":"Heart rhythm."},{"key":"B3","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1016\/j.ipej.2019.02.007","article-title":"Fetal arrhythmias: Diagnosis and management","volume":"19","author":"Batra","year":"2019","journal-title":"Indian Pacing Electrophysiol. 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