Dr. A.D. Kline, M.D. is the Director of Pediatric Genetics in the Harvey Institute for Human Genetics at Greater Baltimore Medical Center. She is an Instructor in Pediatrics at the Johns Hopkins University School of Medicine and Clinical Assistant Professor at the University of Maryland School of Medicine. She is the Medical Director of the Cornelia de Lange Syndrome Foundation.
Natural history of aging in Cornelia de Lange syndrome†
Article first published online: 19 JUL 2007
Copyright © 2007 Wiley-Liss, Inc.
American Journal of Medical Genetics Part C: Seminars in Medical Genetics
Special Issue: Adult Dysmorphology
Volume 145C, Issue 3, pages 248–260, 15 August 2007
How to Cite
Kline, A. D., Grados, M., Sponseller, P., Levy, H. P., Blagowidow, N., Schoedel, C., Rampolla, J., Clemens, D. K., Krantz, I., Kimball, A., Pichard, C. and Tuchman, D. (2007), Natural history of aging in Cornelia de Lange syndrome. Am. J. Med. Genet., 145C: 248–260. doi: 10.1002/ajmg.c.30137
How to cite this article: Kline AD, Grados M, Sponseller P, Levy HP, Blagowidow N, Schoedel C, Rampolla J, Clemens DK, Krantz I, Kimball A, Pichard C, Tuchman D. 2007. Natural history of aging in Cornelia de Lange syndrome. Am J Med Genet Part C Semin Med Genet 145C:248–260.
- Issue published online: 26 JUL 2007
- Article first published online: 19 JUL 2007
- NOIH. Grant Number: RO1 HD039323
- NICHD. Grant Number: PO1 HD052860
- Cornelia de Lange syndrome;
- Barrett esophagus;
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-term 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-injury, anxiety, attention-deficit disorder, autistic features, depression, and obsessive-compulsive 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 NIPBL or SMC1A. Although no specific genotype–phenotype correlations have been firmly established, individuals with missense mutations in NIPBL and SMC1A appear milder than those with other mutations. Based on these observations, recommendations for clinical management of adults with CdLS are made. © 2007 Wiley-Liss, Inc.