{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T17:46:48Z","timestamp":1761760008349,"version":"build-2065373602"},"reference-count":21,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T00:00:00Z","timestamp":1761696000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Multilocus pathogenic variation\u2014when multiple genetic disorders coexist in a single individual\u2014remains rare but is increasingly recognized in the era of genomic medicine. Reporting such cases is essential for improving diagnostic accuracy, refining clinical management, and informing genetic counseling. We describe a pediatric case with a complex phenotype resulting from the coexistence of two distinct genetic diagnoses\u2014cerebrotendinous xanthomatosis (CTX), a rare autosomal recessive lipid storage disorder caused by biallelic mutations in the CYP27A1 gene and Klinefelter syndrome a common sex chromosome aneuploidy occurring in approximately 1 in 600 males, characterized by hypogonadism, gynecomastia, pubertal delay, infertility, micrognathia, and neurodevelopmental challenges\u2014and an additional incidental finding with clinical relevance. The patient was born to consanguineous parents, presented with neurological symptoms, gastrointestinal dysfunction, endocrine abnormalities, and dysmorphic features. Trio-based exome sequencing identified a homozygous pathogenic variant in CYP27A1 consistent with CTX, while conventional G-banded karyotyping revealed a 47,XXY chromosomal pattern, confirming Klinefelter syndrome. Additionally, a heterozygous pathogenic variant in BRCA2 was incidentally detected, associated with hereditary cancer predisposition. The overlapping manifestations of CTX and Klinefelter syndrome produced a non-classical presentation that delayed diagnosis. Although the BRCA2 variant did not contribute to the current phenotype, it has important implications for future cancer surveillance and family risk assessment. This case underscores the importance of combining classical cytogenetic and modern genomic methods to elucidate complex phenotypes, particularly in consanguineous populations, and highlights the need for the multidisciplinary management of patients with multilocus or incidental findings.<\/jats:p>","DOI":"10.3390\/ijms262110510","type":"journal-article","created":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T17:38:22Z","timestamp":1761759502000},"page":"10510","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genomic Confluence: When Cerebrotendinous Xanthomatosis, Klinefelter Syndrome, and a BRCA2 Variant Intersect"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2672-0439","authenticated-orcid":false,"given":"Harry","family":"Pachajoa","sequence":"first","affiliation":[{"name":"Genomic Medicine Laboratory, Department of Basic Medical Sciences, Faculty of Health Sciences, Universidad Icesi, Cali 760031, Colombia"},{"name":"Departamento de Gen\u00e9tica Clinica, Fundaci\u00f3n Valle del Lili, Cali 760032, Colombia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sebasti\u00e1n","family":"Bonilla","sequence":"additional","affiliation":[{"name":"Departamento de Gen\u00e9tica Clinica, Fundaci\u00f3n Valle del Lili, Cali 760032, Colombia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel Andr\u00e9s","family":"Nieva-Posso","sequence":"additional","affiliation":[{"name":"Programa de Medicina, Universidad del Valle, Cali 760042, Colombia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1981","DOI":"10.1016\/j.ajhg.2021.08.009","article-title":"High prevalence of multilocus pathogenic variation in neurodevelopmental disorders in the Turkish population","volume":"108","author":"Mitani","year":"2021","journal-title":"Am. 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