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Clinical and genetic data from 75 individual patients with molecularly confirmed MTS or XLA-MTS were extracted and stratified into two groups: classical MTS (\n                      <jats:italic>TIMM8A<\/jats:italic>\n                      mutations only,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200951) and XLA-MTS (contiguous deletions of\n                      <jats:italic>TIMM8A<\/jats:italic>\n                      and\n                      <jats:italic>BTK<\/jats:italic>\n                      ,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200924). Key clinical features were compared using Fisher\u2019s exact test and Student\u2019s t-test.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Immunodeficiency with agammaglobulinemia (XLA) was present in 100% of XLA-MTS cases (24\/24) versus 0% of classical MTS cases (0\/51). Delayed language development (DLD) was significantly more frequent in XLA-MTS (52,4%, 13\/24) than in classical MTS (19.6%, 10\/51)\n                      <jats:italic>(p<\/jats:italic>\n                      \u2009=\u20090.004). In contrast, progressive cortical blindness (PCB) was markedly more common in classical MTS (58,8%, 30\/51) than in XLA-MTS (12,3%, 3\/24) (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Contiguous deletions encompassing\n                      <jats:italic>TIMM8A<\/jats:italic>\n                      and\n                      <jats:italic>BTK<\/jats:italic>\n                      define a distinct clinical-genetic entity\u2014XLA-MTS\u2014characterized by the triad of early-onset deafness, neurodevelopmental delay, and immunodeficiency. These findings underscore the critical need for expanded genetic testing beyond\n                      <jats:italic>TIMM8A<\/jats:italic>\n                      alone to ensure accurate diagnosis, prognostic stratification, and appropriate clinical management, particularly in patients with syndromic deafness and developmental delay.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13023-026-04447-7","type":"journal-article","created":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T01:36:59Z","timestamp":1782351419000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["XLA-MTS: a distinct clinical genetic entity characterized by immunodeficiency and neurodevelopmental delay"],"prefix":"10.1186","volume":"21","author":[{"given":"Ignacio","family":"Ventura","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"Revert-Ros","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Revert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Carlos","family":"Mar\u00edn-Paya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Ru\u00edz-P\u00e9rez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2726-7963","authenticated-orcid":false,"given":"Jes\u00fas \u00c1ngel","family":"Prieto-Ruiz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Miguel","family":"Hern\u00e1ndez-Andreu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,25]]},"reference":[{"issue":"4","key":"4447_CR1","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1002\/ajmg.a.31079","volume":"140A","author":"LA Aguirre","year":"2006","unstructured":"Aguirre LA, Del Castillo I, Macaya A, Med\u00e1 C, Villamar M, Moreno-Pelayo MA, et al. 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This study is a Comprehensive Clinical Review of previously published literature and did not involve any new data collection from human or animal subjects.","order":1,"name":"Ethics","label":"Institutional review board statement","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable. This study is based on the analysis of previously published case reports and studies, for which informed consent was obtained by the original authors.","order":2,"name":"Ethics","label":"Informed consent","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.","order":3,"name":"Ethics","label":"Conflict of interest","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"323"}}