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Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Defects in both\n                      <jats:italic>CYP21A2<\/jats:italic>\n                      and\n                      <jats:italic>TNXB<\/jats:italic>\n                      genes cause congenital adrenal hyperplasia combined with hypermobility-type Ehlers\u2013Danlos syndrome (EDS), which has been named CAH-X syndrome.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      This study aimed to determine the frequency of CAH-X within the Munich cohort of CAH patients (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a0155: salt wasting = 94, simple virilizing = 44, non-classical = 12, gene carrier = 4, 11\u03b2-deficiency = 1) and assess its clinical implications by thorough clinical characterization of the cohort. In addition, sTNXB protein levels were linked to clinical observations to alleviate potential consequences of mutations such as cardiovascular or joint problems.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design\/setup<\/jats:title>\n                    <jats:p>\n                      PCR screening for the presence of disease-causing variants in\n                      <jats:italic>TNXB<\/jats:italic>\n                      as well as in\n                      <jats:italic>CYP21A2<\/jats:italic>\n                      (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a0155) was conducted; simultaneously, with written consent from the patients (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a076), clinical examinations for joint or skin abnormalities, muscle strength, and neurological functions were performed. CAH-X-positive patients were matched to two control CAH patients according to age and body mass index (BMI). sTNXB protein level estimation, muscle ultrasound, and echocardiography examinations were made on selected CAH-X and CAH patients.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Outcome\/conclusion<\/jats:title>\n                    <jats:p>In our cohort, only 5% carry the CAH-X CH1 chimera. Besides EDS-related clinical symptoms, increased muscle echogenicity compared to unaffected matched controls, particularly in the legs, and cardiac abnormalities that have not been observed in other cohorts and are associated with underlying CAH-X, such as persistent truncus arteriosus and relaxation disorder, were observed. They highlight the importance of genetic as well as clinical screening and regular follow-up examinations for the CAH-X syndrome.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1797669","type":"journal-article","created":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T04:28:17Z","timestamp":1778819297000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Novel cardiac abnormalities observed in CAH patients with tenascin-X haploinsufficiency"],"prefix":"10.3389","volume":"17","author":[{"given":"Andrea","family":"Sappl","sequence":"first","affiliation":[{"name":"Medizinische Klinik IV, LMU Klinikum, Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen","place":["Munich, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annie M.","family":"Sriramachandran","sequence":"additional","affiliation":[{"name":"Medizinische Klinik IV, LMU Klinikum, Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen","place":["Munich, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Lottspeich","sequence":"additional","affiliation":[{"name":"Medizinische Klinik IV, LMU Klinikum, Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen","place":["Munich, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katharina","family":"Vill","sequence":"additional","affiliation":[{"name":"Medizinische Klinik IV, LMU Klinikum, Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen","place":["Munich, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monika","family":"Morak","sequence":"additional","affiliation":[{"name":"Medizinische Klinik IV, LMU Klinikum, Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen","place":["Munich, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ann-Christin","family":"Welp","sequence":"additional","affiliation":[{"name":"Medizinische Klinik IV, LMU Klinikum, Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen","place":["Munich, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Orsela","family":"Dervishi","sequence":"additional","affiliation":[{"name":"Medizinische Klinik IV, LMU Klinikum, Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen","place":["Munich, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Bidlingmaier","sequence":"additional","affiliation":[{"name":"Medizinische Klinik IV, LMU Klinikum, Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen","place":["Munich, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sonja","family":"Kunz","sequence":"additional","affiliation":[{"name":"Medizinische Klinik IV, LMU Klinikum, Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen","place":["Munich, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicole","family":"Reisch","sequence":"additional","affiliation":[{"name":"Medizinische Klinik IV, LMU Klinikum, Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen","place":["Munich, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2012-3148","article-title":"Tenascin-X haploinsufficiency associated with Ehlers-Danlos syndrome in patients with congenital adrenal hyperplasia","volume":"98","author":"Merke","year":"2013","journal-title":"J Clin Endocrinol Metab"},{"key":"B2","doi-asserted-by":"publisher","first-page":"77","DOI":"10.6065\/apem.2346108.054","article-title":"Molecular basis and genetic testing strategies for diagnosing 21-hydroxylase deficiency, including CAH-X syndrome","volume":"28","author":"Kim","year":"2023","journal-title":"Ann Pediatr Endocrinol Metab"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.17.12147","article-title":"Modular variations of the human major histocompatibility complex class III genes for serine\/threonine kinase RP, complement component C4, steroid 21-hydroxylase CYP21, and tenascin TNX (the RCCX module). 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