{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T14:07:11Z","timestamp":1791900431026,"version":"4.3.4"},"reference-count":24,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2006,3,7]],"date-time":"2006-03-07T00:00:00Z","timestamp":1141689600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2006,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>LEOPARD syndrome (LS) is an autosomal dominant syndrome characterized by multiple <jats:styled-content>l<\/jats:styled-content>entigines and caf\u00e9\u2010au\u2010lait spots, electrocardiographic\u2010conduction abnormalities, ocular hypertelorism\/obstructive cardiomyopathy, pulmonary stenosis, abnormalities of the genitalia in males, retardation of growth, and deafness. LS shares many features with Noonan syndrome (NS), in which lentigines and deafness are usually not present. Molecular studies have shown that LS and NS are allelic disorders, caused by different missense mutations in <jats:italic>PTPN11<\/jats:italic>, a gene encoding the protein tyrosine phosphatase SHP\u20102 located at chromosome <jats:italic>12q22\u2010qter<\/jats:italic>. The clinical diagnosis of LS is generally difficult in the first months of life because the distinctive lentigines are generally not present at birth and develop during childhood. From January 2002 to December 2004, we suspected LS clinically in 10 patients admitted to our genetic counseling services in the first 12 months of life. A <jats:italic>PTPN11<\/jats:italic> gene mutation was detected in 8\/10 (80%) patients. In one patient without a <jats:italic>PTPN11<\/jats:italic> mutation a subsequent clinical diagnosis of neurofibromatosis type 1 (NF1) was made, following the evaluation of the mother, who had previously undiagnosed classic NF1. The age of LS patients with <jats:italic>PTPN11<\/jats:italic> mutation ranged between 1 and 11 months (mean age\u2009\u00b1\u2009SD 7.5\u2009\u00b1\u20093.96 months). Review of the clinical characteristics of patients with LS confirmed by molecular study during the first year of life demonstrates that the diagnosis of LS in the first months of age can be clinically suspected in patients presenting with three main features, that is, characteristic facial features (100%), hypertrophic cardiomyopathy (HCM) (87%), and cafe\u2010au\u2010lait spots (75%). Characteristic facial features can be mild or severe, and consist of hypertelorism, downslanting palpebral fissures, ptosis, and dysmorphic ears. The clinical suspicion of LS may be confirmed by molecular screening for <jats:italic>PTPN11<\/jats:italic> mutations. An early diagnosis of the disease is useful for the prospective care of associated medical problems and for precise genetic counseling. \u00a9 2006 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.a.31156","type":"journal-article","created":{"date-parts":[[2006,3,7]],"date-time":"2006-03-07T23:46:57Z","timestamp":1141775217000},"page":"740-746","source":"Crossref","is-referenced-by-count":135,"title":["LEOPARD syndrome: Clinical diagnosis in the first year of life"],"prefix":"10.1002","volume":"140A","author":[{"given":"M. Cristina","family":"Digilio","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Sarkozy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"de Zorzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Pacileo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Limongelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita","family":"Mingarelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raffaele","family":"Calabr\u00f2","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Marino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Dallapiccola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,3,7]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.24.1.9"},{"key":"e_1_2_7_3_1","first-page":"253","volume-title":"Management of genetic syndromes","author":"Allanson JE","year":"2001"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.20023"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02076346"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.34.7.582"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1086\/341528"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1001\/archpedi.1969.02100030654006"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10038-004-0212-x"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2004.021451"},{"key":"e_1_2_7_11_1","doi-asserted-by":"crossref","first-page":"3529","DOI":"10.1210\/jcem.87.8.8694","article-title":"PTPN11 (protein\u2010tyrosine phosphatase, nonreceptor type 11) mutations in seven Japanese patients with Noonan syndrome","volume":"87","author":"Kosaki K","year":"2002","journal-title":"J Clin Endocrinol Metab"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.39.8.571"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.10129"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5200935"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320210310"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.20591"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.30405"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.40.9.704"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2003.013466"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.30773"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1136\/adc.67.2.178"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng772"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1086\/340847"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(76)90764-6"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.30281"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.a.31156","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.31156","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,18]],"date-time":"2023-10-18T06:08:44Z","timestamp":1697609324000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.31156"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,3,7]]},"references-count":24,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2006,4]]}},"alternative-id":["10.1002\/ajmg.a.31156"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.31156","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,3,7]]}}}