{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T16:44:52Z","timestamp":1761324292040,"version":"3.40.5"},"reference-count":13,"publisher":"Walter de Gruyter GmbH","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,5,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec id=\"j_jpem-2019-0494_abs_001_w2aab3b7c36b1b6b1aab1c16b2Aa\">\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder, caused by mutation in <jats:italic>NF1<\/jats:italic>. The condition is typified by the development of benign and malignant tumours in both the central nervous system and peripheral tissues. Isolated menarche is a sub-classification of incomplete isosexual precocious puberty typified by menarche in girls with no other features of pubertal development. The effects of NF1 on pubertal timing are poorly understood, we report two siblings with NF1 and apparent abnormal pubertal development.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_jpem-2019-0494_abs_002_w2aab3b7c36b1b6b1aab1c16b3Aa\">\n                  <jats:title>Case Presentation<\/jats:title>\n                  <jats:p>Two siblings were referred to the tertiary paediatric endocrinology clinic at 6 and 7 years of age with recurrent, cyclical vaginal bleeding. There was a strong family history of NF1, the mother of the siblings and two brothers were also diagnosed at a young age. On examination both patients were prepubertal at presentation. Both siblings underwent a gonadotrophin releasing hormone test, which revealed a follicle-stimulating hormone dominant (prepubertal) response. The features were suggestive of isolated premature menarche as no other cause was identified. The elder sibling established menarche and developed signs of consonant pubertal development at 12 years of age. The younger sibling remains under regular follow-up.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_jpem-2019-0494_abs_003_w2aab3b7c36b1b6b1aab1c16b4Aa\">\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>NF1 has previously been associated with alterations in pubertal timing. We report, for the first time, two siblings with NF1 who presented with isolated menarche.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1515\/jpem-2019-0494","type":"journal-article","created":{"date-parts":[[2020,5,26]],"date-time":"2020-05-26T16:36:13Z","timestamp":1590510973000},"page":"813-816","source":"Crossref","is-referenced-by-count":3,"title":["Isolated premature menarche in two siblings with Neurofibromatosis type 1"],"prefix":"10.1515","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0744-5275","authenticated-orcid":false,"given":"James","family":"Blackburn","sequence":"first","affiliation":[{"name":"Department of Paediatric Endocrinology , Alder Hey Children\u2019s NHS Foundation Trust , Liverpool , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammed","family":"Didi","sequence":"additional","affiliation":[{"name":"Department of Paediatric Endocrinology , Alder Hey Children\u2019s NHS Foundation Trust , Liverpool , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shivaram","family":"Avula","sequence":"additional","affiliation":[{"name":"Department of Radiology , Alder Hey Children\u2019s NHS Foundation Trust , Liverpool , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Senthil","family":"Senniappan","sequence":"additional","affiliation":[{"name":"Department of Paediatric Endocrinology , Alder Hey Children\u2019s Hospital , East Prescot Road , Liverpool, L14 5AB , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"374","published-online":{"date-parts":[[2020,5,21]]},"reference":[{"key":"2023040101344789489_j_jpem-2019-0494_ref_001_w2aab3b7c36b1b6b1ab2b1b1Aa","doi-asserted-by":"crossref","unstructured":"Williams VC, Lucas J, Babcock MA, Gutmann DH, Korf B, Maria BL. Neurofibromatosis Type 1 revisited. Pediatrics 2009;123:124\u201333. https:\/\/doi.org\/10.1542\/peds.2007-3204.","DOI":"10.1542\/peds.2007-3204"},{"key":"2023040101344789489_j_jpem-2019-0494_ref_002_w2aab3b7c36b1b6b1ab2b1b2Aa","doi-asserted-by":"crossref","unstructured":"Viskochil D. Genetics of neurofibromatosis 1 and the NF1 gene. J Child Neurol 2002;17:562\u201370. https:\/\/doi.org\/10.1177\/088307380201700804.","DOI":"10.1177\/088307380201700804"},{"key":"2023040101344789489_j_jpem-2019-0494_ref_003_w2aab3b7c36b1b6b1ab2b1b3Aa","unstructured":"NIH Consensus Statement. Neurofibromatosis. Jul 13-15; 1987;6:1\u201319."},{"key":"2023040101344789489_j_jpem-2019-0494_ref_004_w2aab3b7c36b1b6b1ab2b1b4Aa","doi-asserted-by":"crossref","unstructured":"Hirbe AC, Gutmann DH. Neurofibromatosis type 1: a multidisciplinary approach to care. 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