{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T13:43:49Z","timestamp":1762868629144},"reference-count":20,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,9,6]],"date-time":"2021-09-06T00:00:00Z","timestamp":1630886400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,9,6]],"date-time":"2021-09-06T00:00:00Z","timestamp":1630886400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"zhejiang province health innovative talents project","award":["2021KY762"],"award-info":[{"award-number":["2021KY762"]}]},{"DOI":"10.13039\/501100001809","name":"national natural sience foundation of china","doi-asserted-by":"crossref","award":["NSFC81501295"],"award-info":[{"award-number":["NSFC81501295"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Hereditas"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>LEOPARD syndrome (OMIM #151,100) caused by a germline PTPN11 mutation are characterized as multisystemic anomalies and variable marked phenotypes such as multiple lentigines and cafe\u00b4-au-lait spots, electrocardiographic conduction abnormalities, ocular hypertelorism\/obstructive cardiomyopathy, pulmonary stenosis, abnormal genitalia, retardation of growth, and deafness. Phenotype overlap complicates clinical discrimination within RASopathies, making the diagnosis of LEOPARD more confusing and challenging. Besides, LEOPARD patients do not usually present with all these typical clinical features, increasing the possibility of underdiagnosis or misdiagnosis.<\/jats:p><jats:p>Herein, we report a case of LEOPARD syndrome in a patient who only presented with pigmented skin spots and was initially diagnosed with multiple acquired melanocytic nevi. Subsequent pathological examination confirmed the diagnosis of multiple lentigines rather than melanocytic nevi. A genetic study showed a germline PTPN11 (Tyr279Cys) mutation and raised the suspicion of LEOPARD syndrome. A subsequent ECG examination detected potential cardiac defects and confirmed the diagnosis of LEOPARD. We considered that the potential damage of other systems underlying the skin multiple lentigines should not be ignored. The diagnosis of LEOPARD syndrome in an early stage before cardiac damage has reached a serious and irreversible stage can be meaningful for patients to fully understand the potential risks, complications and prognosis of the disease and to take appropriate precautions to prevent the potential risk of cardiac damage.<\/jats:p>","DOI":"10.1186\/s41065-021-00199-5","type":"journal-article","created":{"date-parts":[[2021,9,6]],"date-time":"2021-09-06T13:02:59Z","timestamp":1630933379000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Leopard syndrome: the potential cardiac defect underlying skin phenotypes"],"prefix":"10.1186","volume":"158","author":[{"given":"Xiaojie","family":"Yue","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiong","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yefeng","family":"Dai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lan","family":"Yu.","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,9,6]]},"reference":[{"issue":"6","key":"199_CR1","doi-asserted-by":"publisher","first-page":"652","DOI":"10.1001\/archpedi.1969.02100030654006","volume":"117","author":"RJ Gorlin","year":"1969","unstructured":"Gorlin RJ, Anderson RC, Blaw M. Multiple lentigenes syndrome. Am J Dis Child. 1969;117(6):652\u201362. https:\/\/doi.org\/10.1001\/archpedi.1969.02100030654006.","journal-title":"Am J Dis Child"},{"issue":"7","key":"199_CR2","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1136\/jmg.34.7.582","volume":"34","author":"BD Coppin","year":"1997","unstructured":"Coppin BD, Temple IK. Multiple lentigines syndrome (LEOPARD syndrome or progressive cardiomyopathic lentiginosis). J Med Genet. 1997;34(7):582\u20136. https:\/\/doi.org\/10.1136\/jmg.34.7.582.","journal-title":"J Med Genet"},{"issue":"3","key":"199_CR3","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1016\/0002-9343(76)90764-6","volume":"60","author":"DA Voron","year":"1976","unstructured":"Voron DA, Hatfield HH, Kalkhoff RK. Multiple lentigines syndrome: case report and review of the literature. Am J Med. 1976;60(3):447\u201356. https:\/\/doi.org\/10.1016\/0002-9343(76)90764-6.","journal-title":"Am J Med"},{"issue":"4","key":"199_CR4","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1288\/00005537-197110000-00015","volume":"7","author":"RJ Gorlin","year":"1971","unstructured":"Gorlin RJ, Anderson RC, Moller JH. The Leopard (multiple lentigines) syndrome revisited. Birth Defects Orig Artic Ser. 1971;7(4):110\u20135. https:\/\/doi.org\/10.1288\/00005537-197110000-00015.","journal-title":"Birth Defects Orig Artic Ser"},{"issue":"3","key":"199_CR5","doi-asserted-by":"publisher","first-page":"2639","DOI":"10.3892\/mmr.2016.5547","volume":"14","author":"J Zhang","year":"2016","unstructured":"Zhang J, Shen J, Cheng R, et al. Identification of a PTPN11 hot spot mutation in a child with atypical LEOPARD syndrome. Mol Med Rep. 2016;14(3):2639\u201343. https:\/\/doi.org\/10.3892\/mmr.2016.5547.","journal-title":"Mol Med Rep"},{"issue":"2","key":"199_CR6","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1046\/j.1525-1470.2003.20214.x7","volume":"20","author":"WW Choi","year":"2003","unstructured":"Choi WW, Yoo JY, Park KC, Kim KH. LEOPARD syndrome with a new association of congenital corneal tumor, choristoma. Pediatr Dermatol. 2003;20(2):158\u201360. https:\/\/doi.org\/10.1046\/j.1525-1470.2003.20214.x7.","journal-title":"Pediatr Dermatol"},{"issue":"7","key":"199_CR7","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1016\/j.ad.2019.01.017","volume":"111","author":"MF Garc\u00eda Gil","year":"2020","unstructured":"Garc\u00eda Gil MF, \u00c1lvarez Salafranca M, Valero Torres A, Ara Mart\u00edn M. Melanoma in noonan syndrome with multiple lentigines (leopard syndrome) a new case. melanoma en el s\u00edndrome de Noonan con lentigos m\u00faltiples (s\u00edndrome de LEOPARD): presentaci\u00f3n de un nuevo caso. Actas Dermosifiliogr Engl Ed. 2020;111(7):619\u201321. https:\/\/doi.org\/10.1016\/j.ad.2019.01.017.","journal-title":"Actas Dermosifiliogr Engl Ed"},{"issue":"9","key":"199_CR8","doi-asserted-by":"publisher","first-page":"1328","DOI":"10.1161\/CIRCULATIONAHA.108.792861","volume":"119","author":"L Lehmann","year":"2009","unstructured":"Lehmann L, Schufele T, Buss S, et al. IMAGE CARDIO MED. A patient with LEOPARD syndrome and PTPN11 mutation. Circulation. 2009;119(9):1328\u20139. https:\/\/doi.org\/10.1161\/CIRCULATIONAHA.108.792861.","journal-title":"Circulation"},{"key":"199_CR9","doi-asserted-by":"publisher","unstructured":"Limongelli G, Sarkozy A, Pacileo G, et al. Genotype phenotype analysis and natural history of left ventricular hypertrophy in LEOPARD syndrome. 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Written informed consent to participate was obtained.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Written informed consent for publication was obtained.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare there is no conflicts of interest regarding the publication of this paper. The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"34"}}