{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T16:59:14Z","timestamp":1788973154296,"version":"build-2803163510"},"reference-count":48,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2007,7,19]],"date-time":"2007-07-19T00:00:00Z","timestamp":1184803200000},"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 C"],"published-print":{"date-parts":[[2007,8,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Observations about the natural history of aging in Cornelia de Lange syndrome (CdLS) are made, based on 49 patients from a multidisciplinary clinic for adolescents and adults. The mean age was 17 years. Although most patients remain small, obesity may develop. Gastroesophageal reflux persists or worsens, and there are early long\u2010term sequelae, including Barrett esophagus in 10%; other gastrointestinal findings include risk for volvulus, rumination, and chronic constipation. Submucous cleft palate was found in 14%, most undetected before our evaluation. Chronic sinusitis was noted in 39%, often with nasal polyps. Blepharitis improves with age; cataracts and detached retina may occur. Decreased bone density is observed, with occasional fractures. One quarter have leg length discrepancy and 39% scoliosis. Most females have delayed or irregular menses but normal gynecologic exams and pap smears. Benign prostatic hypertrophy occurred in one male prior to 40 years. The phenotype is variable, but there is a distinct pattern of facial changes with aging. Premature gray hair is frequent; two patients had cutis verticis gyrata. Behavioral issues and specific psychiatric diagnoses, including self\u2010injury, anxiety, attention\u2010deficit disorder, autistic features, depression, and obsessive\u2010compulsive behavior, often worsen with age. This work presents some evidence for accelerated aging in CdLS. Of 53% with mutation analysis, 55% demonstrate a detectable mutation in <jats:italic>NIPBL<\/jats:italic> or <jats:italic>SMC1A<\/jats:italic>. Although no specific genotype\u2013phenotype correlations have been firmly established, individuals with missense mutations in <jats:italic>NIPBL<\/jats:italic> and <jats:italic>SMC1A<\/jats:italic> appear milder than those with other mutations. Based on these observations, recommendations for clinical management of adults with CdLS are made. \u00a9 2007 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.c.30137","type":"journal-article","created":{"date-parts":[[2007,7,19]],"date-time":"2007-07-19T18:16:57Z","timestamp":1184869017000},"page":"248-260","source":"Crossref","is-referenced-by-count":141,"title":["Natural history of aging in Cornelia de Lange syndrome"],"prefix":"10.1002","volume":"145C","author":[{"given":"Antonie D.","family":"Kline","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Grados","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Sponseller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Howard P.","family":"Levy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie","family":"Blagowidow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christianne","family":"Schoedel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joni","family":"Rampolla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas K.","family":"Clemens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"Krantz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Kimball","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Pichard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Tuchman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2007,7,19]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.34.8.645"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.30984"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/adc.81.4.333"},{"key":"e_1_2_7_5_1","first-page":"568","article-title":"Genotype\u2013phenotype correlations of 39 patients with Cornelia de Lange syndrome: The Dutch experience","volume":"40","author":"Bhuiyan ZA","year":"2006","journal-title":"J Med Genet"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.mog.0000231816.18396.26"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20380"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.30399"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.1992.tb03628.x"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1086\/511888"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.MLG.0000163751.00885.63"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.02064"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.AOG.0000160512.24767.08"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004836-199603000-00012"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11894-006-0075-8"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/1531-8257(200007)15:4<749::AID-MDS1028>3.0.CO;2-P"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1086\/424698"},{"key":"e_1_2_7_18_1","first-page":"530","article-title":"Total hip reconstruction in a woman with Cornelia de Lange syndrome: A case report","volume":"89","author":"Grant RE","year":"1997","journal-title":"J Natl Med Assoc"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320030402"},{"key":"e_1_2_7_20_1","first-page":"1559","article-title":"Cecal volvulus as a complication in Cornelia de Lange syndrome. 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