{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T23:43:13Z","timestamp":1782603793486,"version":"3.54.5"},"reference-count":43,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2018,9,21]],"date-time":"2018-09-21T00:00:00Z","timestamp":1537488000000},"content-version":"vor","delay-in-days":20,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2018,9]]},"abstract":"<jats:p>Noonan syndrome (NS), the most common of the RASopathies, is a developmental disorder caused by heterozygous germline mutations in genes encoding proteins in the RAS\u2010MAPK signaling pathway. Noonan\u2010like syndrome with loose anagen hair (NSLH, including NSLH1, OMIM #607721 and NSLH2, OMIM #617506) is characterized by typical features of NS with additional findings of macrocephaly, loose anagen hair, growth hormone deficiency in some, and a higher incidence of intellectual disability. All NSLH1 reported cases to date have had an<jats:italic>SHOC2<\/jats:italic>c.4A&gt;G, p.Ser2Gly mutation; NSLH2 cases have been reported with a<jats:italic>PPP1CB<\/jats:italic>c.146G&gt;C, p.Pro49Arg mutation, or c.166G&gt;C, p.Ala56Pro mutation. True cleft palate does not appear to have been previously reported in individuals with NS or with NSLH. While some patients with NS have had growth hormone deficiency (GHD), other endocrine abnormalities are only rarely documented. We present a female patient with NSLH1 who was born with a posterior cleft palate, micrognathia, and mild hypotonia. Other findings in her childhood and young adulthood years include hearing loss, strabismus, and hypopituitarism with growth hormone, thyroid stimulating hormone (TSH), and gonadotropin deficiencies. The<jats:italic>SHOC2<\/jats:italic>mutation may be responsible for this patient's additional features of cleft palate and hypopituitarism.<\/jats:p>","DOI":"10.1002\/ajmg.a.40432","type":"journal-article","created":{"date-parts":[[2018,9,22]],"date-time":"2018-09-22T01:56:02Z","timestamp":1537581362000},"page":"2024-2027","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Cleft palate and hypopituitarism in a patient with Noonan\u2010like syndrome with loose anagen hair\u20101"],"prefix":"10.1002","volume":"176","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8713-2097","authenticated-orcid":false,"given":"Natario L.","family":"Couser","sequence":"first","affiliation":[{"name":"Department of Ophthalmology University of North Carolina School of Medicine Chapel Hill North Carolina"},{"name":"Department of Pediatrics, Division of Genetics and Metabolism University of North Carolina School of Medicine Chapel Hill North Carolina"},{"name":"Department of Ophthalmology Virginia Commonwealth University School of Medicine Richmond Virginia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debra","family":"Keelean\u2010Fuller","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Genetics and Metabolism University of North Carolina School of Medicine Chapel Hill North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marsha L.","family":"Davenport","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Pediatric Endocrinology and Diabetes University of North Carolina School of Medicine Chapel Hill North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eden","family":"Haverfield","sequence":"additional","affiliation":[{"name":"GeneDx Gaithersburg Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maheer M.","family":"Masood","sequence":"additional","affiliation":[{"name":"University of North Carolina School of Medicine Chapel Hill North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Henin","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Pediatric Endocrinology and Diabetes University of North Carolina School of Medicine Chapel Hill North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arthur S.","family":"Aylsworth","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Genetics and Metabolism University of North Carolina School of Medicine Chapel Hill North Carolina"},{"name":"Department of Genetics University of North Carolina School of Medicine Chapel Hill North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,9,21]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semarthrit.2013.04.009"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.38070"},{"issue":"1","key":"e_1_2_6_4_1","first-page":"37","article-title":"Noonan syndrome","volume":"89","author":"Bhambhani V.","year":"2014","journal-title":"American Family Physician"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/ocr.12144"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.35234"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/1824-7288-38-48"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2014.11.017"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.425"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22834"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.33987"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22026"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddu148"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37082"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36376"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37781"},{"issue":"10","key":"e_1_2_6_17_1","doi-asserted-by":"crossref","first-page":"2420","DOI":"10.1002\/ajmg.a.36098","article-title":"Expanding the SHOC2 mutation associated phenotype of Noonan syndrome with loose anagen hair: Structural brain anomalies and myelofibrosis","volume":"161","author":"Gripp K. 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