{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,8]],"date-time":"2025-07-08T11:08:03Z","timestamp":1751972883258},"reference-count":23,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,3,4]],"date-time":"2021-03-04T00:00:00Z","timestamp":1614816000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,3,4]],"date-time":"2021-03-04T00:00:00Z","timestamp":1614816000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Ital J Pediatr"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Central precocious puberty is a condition characterized by precocious activation of the hypothalamic-pituitary-gonadal axis. It may be idiopathic or secondary to organic causes, including syndromes such as Neurofibromatosis type 1 (NF1).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Case presentation<\/jats:title>\n                <jats:p>We presented a girl of 6\u2009years and 10\u2009months with almost 11 caf\u00e9-au-lait skin macules, without other clinical or radiological signs typical of NF1, and with a central precocious puberty. Genetic analysis evidenced the new variant NM-152594.2:c.304delAp. (Thr102Argfs*19) in <jats:italic>SPRED1<\/jats:italic> gene, which allowed to diagnose Legius syndrome.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>We report for the first time a case of central precocious puberty in a girl with Legius syndrome. The presence of central precocious puberty in a child with characteristic caf\u00e9-au-lait macules should suggest pediatricians to perform genetic analysis in order to reach a definitive diagnosis. Further studies on timing of puberty in patients with RASopathies are needed to better elucidate if this clinical association is casual or secondary to their clinical condition.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13052-021-01004-9","type":"journal-article","created":{"date-parts":[[2021,3,4]],"date-time":"2021-03-04T17:02:44Z","timestamp":1614877364000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Central precocious puberty in a girl with LEGIUS syndrome: an accidental association?"],"prefix":"10.1186","volume":"47","author":[{"given":"Valentina","family":"Orlandi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paolo","family":"Cavarzere","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Palma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rossella","family":"Gaudino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Franco","family":"Antoniazzi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,3,4]]},"reference":[{"key":"1004_CR1","doi-asserted-by":"publisher","first-page":"2366","DOI":"10.1056\/NEJMcp0800459","volume":"358","author":"JC Carel","year":"2008","unstructured":"Carel JC, L\u00e9ger J. Clinical practice Precocious puberty. N Engl J Med. 2008;358:2366\u201377.","journal-title":"N Engl J Med"},{"key":"1004_CR2","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1016\/j.bpobgyn.2017.11.004","volume":"48","author":"C Sultan","year":"2018","unstructured":"Sultan C, Gaspari L, Maimoun L, Kalfa N, Paris F. Disorders of puberty. Best Pract Res Clin Obstet Gynaecol. 2018;48:62\u201389.","journal-title":"Best Pract Res Clin Obstet Gynaecol"},{"issue":"2","key":"1004_CR3","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1007\/s12519-013-0411-7","volume":"9","author":"DB Brown","year":"2013","unstructured":"Brown DB, Loomba-Albrecht LA, Bremer AA. Sexual precocity and its treatment. World J Pediatr. 2013;9(2):103\u201311.","journal-title":"World J Pediatr"},{"issue":"4","key":"1004_CR4","first-page":"164","volume":"1","author":"M Berbero\u011flu","year":"2009","unstructured":"Berbero\u011flu M. 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In our country, namely Italy, this type of clinical study does not require Institutional Review Board\/Institutional Ethics Committee approval to publish the results.The authors have obtained consent to publish from the parents of the children.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"The authors have obtained consent to publish from the parents of the children.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that there are no competing interests or conflicts of interest that could be perceived as prejudicing the impartiality of the affirmation reported.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"50"}}