{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T18:51:57Z","timestamp":1791571917150,"version":"4.3.4"},"reference-count":19,"publisher":"Springer Science and Business Media LLC","issue":"11","license":[{"start":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T00:00:00Z","timestamp":1791504000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T00:00:00Z","timestamp":1791504000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur J Pediatr"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    X-linked ichthyosis is caused by pathogenic variants or deletions involving\n                    <jats:italic>STS<\/jats:italic>\n                    at Xp22.31. Because some deletions include contiguous genes and cardiac rhythm abnormalities have been reported, we characterized the cardiac phenotype of children with genetically confirmed steroid sulfatase-related syndromic epidermal differentiation disorder (\n                    <jats:italic>STS<\/jats:italic>\n                    -sEDD). This prospective, observational, single-centre study included 14 boys aged 2\u201316\u00a0years. Assessment comprised clinical history and examination, 12-lead electrocardiography, echocardiography, exercise testing when age-appropriate, and 5-day ambulatory electrocardiographic monitoring. Genetic findings were reviewed, and 11 obligate-carrier mothers also underwent cardiological assessment. Nine patients (64%) were asymptomatic and five (36%) reported mild, nonspecific symptoms. Minor electrocardiographic findings in 11 patients were considered age-appropriate variants. All hearts were structurally normal except for one previously known, haemodynamically compensated partial anomalous pulmonary venous return. Exercise testing in 12 patients identified one isolated premature ventricular contraction; 5-day monitoring in 13 detected no clinically significant arrhythmia. Twelve patients had contiguous-gene deletions and two had pathogenic\n                    <jats:italic>STS<\/jats:italic>\n                    sequence variants, with no apparent association between deletion extent and cardiac findings. Maternal echocardiograms were normal; one mother had isolated atrial and ventricular ectopy during exercise without clinically significant arrhythmia.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:italic>Conclusion<\/jats:italic>\n                    : Clinically relevant cardiac involvement appeared uncommon in this small pediatric cohort. The sample size and cross-sectional assessment preclude definitive risk estimates; cardiological evaluation should be individualized according to symptoms, cardiovascular findings, and family history.\n                    <jats:table-wrap>\n                      <jats:table>\n                        <jats:tbody>\n                          <jats:tr>\n                            <jats:td align=\"left\">\n                              <jats:bold>What is Known:<\/jats:bold>\n                              \u2022\n                              <jats:italic>X-linked ichthyosis is caused by STS variants or deletions that may involve contiguous genes.<\/jats:italic>\n                              \u2022\n                              <jats:italic>Cardiac arrhythmias have been reported with Xp22.31 deletions, but pediatric data are scarce.<\/jats:italic>\n                            <\/jats:td>\n                          <\/jats:tr>\n                          <jats:tr>\n                            <jats:td align=\"left\">\n                              <jats:bold>What is New:<\/jats:bold>\n                              \u2022\n                              <jats:italic>No clinically significant arrhythmia was found in 14 boys undergoing multimodal assessment.<\/jats:italic>\n                              \u2022\n                              <jats:italic>Deletion extent did not predict cardiac findings; follow-up should reflect symptoms and family history.<\/jats:italic>\n                            <\/jats:td>\n                          <\/jats:tr>\n                        <\/jats:tbody>\n                      <\/jats:table>\n                    <\/jats:table-wrap>\n                  <\/jats:p>","DOI":"10.1007\/s00431-026-07488-z","type":"journal-article","created":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T18:08:06Z","timestamp":1791569286000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cardiac phenotype in children with X-linked ichthyosis (STS-sEDD): findings from a prospective cohort"],"prefix":"10.1007","volume":"185","author":[{"given":"Katia","family":"Henostroza Inga","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2863-3195","authenticated-orcid":false,"given":"Andrea","family":"Greco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Estefan\u00eda","family":"Mart\u00ednez-Barrios","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9","family":"Cruzalegui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuria","family":"D\u00edez-Escut\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Ehrenberg Archs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Valero Mart\u00edn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz","family":"M\u00ednguez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Bov\u00e9 Guri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgia","family":"Sarquella-Brugada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eulalia","family":"Baselga Torres","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,10,9]]},"reference":[{"key":"7488_CR1","doi-asserted-by":"publisher","first-page":"692","DOI":"10.1136\/jmedgenet-2019-106676","volume":"57","author":"L Brcic","year":"2020","unstructured":"Brcic L, Underwood JF, Kendall KM, Caseras X, Kirov G, Davies W (2020) Medical and neurobehavioural phenotypes in carriers of X-linked ichthyosis-associated genetic deletions in the UK Biobank. J Med Genet 57:692\u2013698. https:\/\/doi.org\/10.1136\/jmedgenet-2019-106676","journal-title":"J Med Genet"},{"key":"7488_CR2","doi-asserted-by":"publisher","first-page":"544","DOI":"10.1093\/bjd\/ljaf065","volume":"193","author":"\u00c1 Hern\u00e1ndez-Mart\u00edn","year":"2025","unstructured":"Hern\u00e1ndez-Mart\u00edn \u00c1, Paller AS, Sprecher E et al (2025) A proposal for a new pathogenesis-guided classification for inherited epidermal differentiation disorders. Br J Dermatol 193:544\u2013548. https:\/\/doi.org\/10.1093\/bjd\/ljaf065","journal-title":"Br J Dermatol"},{"key":"7488_CR3","doi-asserted-by":"publisher","first-page":"592","DOI":"10.1093\/bjd\/ljaf123","volume":"193","author":"AS Paller","year":"2025","unstructured":"Paller AS, Teng J, Mazereeuw-Hautier J et al (2025) Syndromic epidermal differentiation disorders: a new classification toward pathogenesis-based therapy. Br J Dermatol 193:592\u2013618. https:\/\/doi.org\/10.1093\/bjd\/ljaf123","journal-title":"Br J Dermatol"},{"key":"7488_CR4","doi-asserted-by":"publisher","first-page":"1876","DOI":"10.1093\/ced\/llaf221","volume":"50","author":"W Davies","year":"2025","unstructured":"Davies W (2025) The importance of cardiac screening in X-linked ichthyosis: a plea. Clin Exp Dermatol 50:1876\u20131877. https:\/\/doi.org\/10.1093\/ced\/llaf221","journal-title":"Clin Exp Dermatol"},{"key":"7488_CR5","doi-asserted-by":"publisher","first-page":"1370","DOI":"10.21037\/tp-2025-87","volume":"14","author":"IS Dantsev","year":"2025","unstructured":"Dantsev IS, Buianova AA, Polykova EB, Nikolaeva EA, Vasilyev EV, Yakshina AI, Parfenenko MA, Yablonskaya MI, Kurinnaia OS, Iourov IY (2025) Cardiac arrhythmia, developmental delay, epilepsy and ichthyosis due to Xp22.31 deletion: review of literature and case report. Transl Pediatr 14:1370\u20131379. https:\/\/doi.org\/10.21037\/tp-2025-87","journal-title":"Transl Pediatr"},{"key":"7488_CR6","doi-asserted-by":"publisher","DOI":"10.1016\/j.xjidi.2022.100109","volume":"2","author":"L Brcic","year":"2022","unstructured":"Brcic L, Wren GH, Underwood JFG, Kirov G, Davies W (2022) Comorbid medical issues in X-linked ichthyosis. JID Innov 2:100109. https:\/\/doi.org\/10.1016\/j.xjidi.2022.100109","journal-title":"JID Innov"},{"key":"7488_CR7","doi-asserted-by":"publisher","first-page":"2944","DOI":"10.1002\/ajmg.a.32473","volume":"146A","author":"MAM van Steensel","year":"2008","unstructured":"van Steensel MAM, Vreeburg M, Engelen J, Ghesquiere S, Stegmann APA, Herbergs J, van Lent J, Smeets B, Vles JH (2008) Contiguous gene syndrome due to a maternally inherited 8.41 Mb distal deletion of chromosome band Xp22.3 in a boy with short stature, ichthyosis, epilepsy, mental retardation, cerebral cortical heterotopias and Dandy\u2013Walker malformation. American J of Med Genetics Pt A 146A:2944\u20132949. https:\/\/doi.org\/10.1002\/ajmg.a.32473","journal-title":"American J of Med Genetics Pt A"},{"key":"7488_CR8","doi-asserted-by":"publisher","first-page":"636","DOI":"10.1136\/jmg-2022-108862","volume":"60","author":"G Wren","year":"2023","unstructured":"Wren G, Baker E, Underwood J, Humby T, Thompson A, Kirov G, Escott-Price V, Davies W (2023) Characterising heart rhythm abnormalities associated with Xp22.31 deletion. J Med Genet 60:636\u2013643. https:\/\/doi.org\/10.1136\/jmg-2022-108862","journal-title":"J Med Genet"},{"key":"7488_CR9","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1042\/ebc20230098","volume":"68","author":"GH Wren","year":"2024","unstructured":"Wren GH, Davies W (2024) Cardiac arrhythmia in individuals with steroid sulfatase deficiency (X-linked ichthyosis): candidate anatomical and biochemical pathways. Essays Biochem 68:423\u2013429. https:\/\/doi.org\/10.1042\/ebc20230098","journal-title":"Essays Biochem"},{"key":"7488_CR10","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1038\/s41436-019-0686-8","volume":"22","author":"ER Riggs","year":"2020","unstructured":"Riggs ER, Andersen EF, Cherry AM et al (2020) Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med 22:245\u2013257. https:\/\/doi.org\/10.1038\/s41436-019-0686-8","journal-title":"Genet Med"},{"key":"7488_CR11","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1038\/gim.2015.30","volume":"17","author":"S Richards","year":"2015","unstructured":"Richards S, Aziz N, Bale S et al (2015) Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 17:405\u2013424. https:\/\/doi.org\/10.1038\/gim.2015.30","journal-title":"Genet Med"},{"key":"7488_CR12","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1016\/s0006-8993(97)00867-6","volume":"773","author":"ME Rhodes","year":"1997","unstructured":"Rhodes ME, Li PK, Burke AM, Johnson DA (1997) Enhanced plasma DHEAS, brain acetylcholine and memory mediated by steroid sulfatase inhibition. Brain Res 773:28\u201332. https:\/\/doi.org\/10.1016\/s0006-8993(97)00867-6","journal-title":"Brain Res"},{"key":"7488_CR13","doi-asserted-by":"publisher","first-page":"2545","DOI":"10.1210\/jc.2015-4101","volume":"101","author":"J Idkowiak","year":"2016","unstructured":"Idkowiak J, Taylor AE, Subtil S et al (2016) Steroid sulfatase deficiency and androgen activation before and after puberty. J Clin Endocrinol Metab 101:2545\u20132553. https:\/\/doi.org\/10.1210\/jc.2015-4101","journal-title":"J Clin Endocrinol Metab"},{"key":"7488_CR14","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1177\/2047487312467903","volume":"21","author":"BP Krijthe","year":"2014","unstructured":"Krijthe BP, de Jong FH, Hofman A, Franco OH, Witteman JC, Stricker BH, Heeringa J (2014) Dehydroepiandrosterone sulfate levels and risk of atrial fibrillation: the Rotterdam Study. Eur J Prev Cardiol 21:291\u2013298. https:\/\/doi.org\/10.1177\/2047487312467903","journal-title":"Eur J Prev Cardiol"},{"key":"7488_CR15","doi-asserted-by":"publisher","DOI":"10.1016\/j.mbplus.2021.100059","volume":"11","author":"DL Rebolledo","year":"2021","unstructured":"Rebolledo DL, Lipson KE, Brandan E (2021) Driving fibrosis in neuromuscular diseases: role and regulation of connective tissue growth factor (CCN2\/CTGF). Matrix Biol Plus 11:100059. https:\/\/doi.org\/10.1016\/j.mbplus.2021.100059","journal-title":"Matrix Biol Plus"},{"key":"7488_CR16","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1161\/circulationaha.121.054108","volume":"145","author":"BA Aguado","year":"2022","unstructured":"Aguado BA, Walker CJ, Grim JC et al (2022) Genes that escape X chromosome inactivation modulate sex differences in valve myofibroblasts. Circulation 145:513\u2013530. https:\/\/doi.org\/10.1161\/circulationaha.121.054108","journal-title":"Circulation"},{"key":"7488_CR17","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2022.104459","volume":"65","author":"G Wren","year":"2022","unstructured":"Wren G, Davies W (2022) Sex-linked genetic mechanisms and atrial fibrillation risk. Eur J Med Genet 65:104459. https:\/\/doi.org\/10.1016\/j.ejmg.2022.104459","journal-title":"Eur J Med Genet"},{"key":"7488_CR18","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1515\/tnsci-2019-0030","volume":"10","author":"T Humby","year":"2019","unstructured":"Humby T, Davies W (2019) Brain gene expression in a novel mouse model of postpartum mood disorder. Transl Neurosci 10:168\u2013174. https:\/\/doi.org\/10.1515\/tnsci-2019-0030","journal-title":"Transl Neurosci"},{"key":"7488_CR19","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1005679","volume":"12","author":"M Kohda","year":"2016","unstructured":"Kohda M, Tokuzawa Y, Kishita Y et al (2016) A comprehensive genomic analysis reveals the genetic landscape of mitochondrial respiratory chain complex deficiencies. PLoS Genet 12:e1005679. https:\/\/doi.org\/10.1371\/journal.pgen.1005679","journal-title":"PLoS Genet"}],"container-title":["European Journal of Pediatrics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00431-026-07488-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00431-026-07488-z","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00431-026-07488-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T18:08:07Z","timestamp":1791569287000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00431-026-07488-z"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,9]]},"references-count":19,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2026,11]]}},"alternative-id":["7488"],"URL":"https:\/\/doi.org\/10.1007\/s00431-026-07488-z","relation":{},"ISSN":["1432-1076"],"issn-type":[{"value":"1432-1076","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,9]]},"assertion":[{"value":"2 August 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 September 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 October 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 October 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Hospital Sant Joan de Deu Barcelona (PIC-108\u201323).","order":1,"name":"Ethics","label":"Ethics approval","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Written informed consent to participate was obtained from the parents or legal guardians of all pediatric participants and from participating adult mothers.","order":2,"name":"Ethics","label":"Consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Written informed consent for publication of the clinical images was obtained from a parent or legal guardian of the participant shown.","order":3,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors completed the STROBE checklist for this observational study.","order":5,"name":"Ethics","label":"Reporting guideline","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"823"}}