{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T14:54:15Z","timestamp":1785250455917,"version":"3.55.0"},"reference-count":60,"publisher":"S. Karger AG","license":[{"start":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T00:00:00Z","timestamp":1774828800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T00:00:00Z","timestamp":1774828800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Horm Res Paediatr"],"abstract":"<jats:p>Introduction: Central precocious puberty (CPP) is rare in boys, and idiopathic forms are particularly uncommon. This study characterizes the genetic architecture of idiopathic CPP (ICPP) in a national cohort of boys. Methods: We conducted a retrospective and prospective study of boys with ICPP recorded in the Portuguese national registry over the past 2 decades. Clinical, laboratory, and demographic characteristics of the patients were reviewed. Whole-exome sequencing (WES) was performed to identify pathogenic variants. Results: Of 736 children with CPP, 8.2% were males. Total CPP cases in boys increased significantly over time (p &lt; 0.001), particularly during COVID-19. While secondary CPP remained stable (p = 0.198), idiopathic forms increased by 19.1%\/year (p &lt; 0.001), with change points in 2011 and 2021. WES identified pathogenic MKRN3 variants in 13.3% (2\/15) boys, including a novel variant (p.Asp267Asn). MKRN3-positive patients presented with later-onset puberty, though sample size limits definitive conclusions. WES also detected a clinically significant TP53 variant as an incidental finding. Conclusion: ICPP incidence in Portuguese boys increased significantly over 2 decades, with acceleration during the pandemic. While genetic causes (primarily MKRN3 variants) were identified in 13.3% of cases, the substantial proportion of unexplained cases and temporal clustering indicate important roles for environmental and epigenetic factors.<\/jats:p>","DOI":"10.1159\/000551720","type":"journal-article","created":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T16:00:59Z","timestamp":1774886459000},"page":"1-10","source":"Crossref","is-referenced-by-count":2,"title":["Idiopathic Central Precocious Puberty in Boys: Results from a National Portuguese 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