How to Cite this Article: Rohatgi S, Clark D, Kline AD, Jackson LG, Pie J, Siu V, Ramos FJ, Krantz ID, Deardorff MA. 2010. Facial diagnosis of mild and variant CdLS: Insights from a dysmorphologist survey. Am J Med Genet Part A 152A:1641–1653.
Facial diagnosis of mild and variant CdLS: Insights from a dysmorphologist survey†
Article first published online: 25 JUN 2010
Copyright © 2010 Wiley-Liss, Inc.
American Journal of Medical Genetics Part A
Volume 152A, Issue 7, pages 1641–1653, July 2010
How to Cite
Rohatgi, S., Clark, D., Kline, A. D., Jackson, L. G., Pie, J., Siu, V., Ramos, F. J., Krantz, I. D. and Deardorff, M. A. (2010), Facial diagnosis of mild and variant CdLS: Insights from a dysmorphologist survey. Am. J. Med. Genet., 152A: 1641–1653. doi: 10.1002/ajmg.a.33441
- Issue published online: 25 JUN 2010
- Article first published online: 25 JUN 2010
- Manuscript Accepted: 8 MAR 2010
- Manuscript Received: 16 JAN 2010
- NIH. Grant Numbers: NICHD K08 KHD055488A, NICHD 5P30HD026979, NICHD PO1 HD052860
- Ministerio de Sanidad y Consumo-ISCIII-FIS. Grant Number: PI061343
- Gobierno de Aragón-Grupo de Investigación Consolidado. Grant Number: B23
- Cornelia de Lange syndrome;
- Brachmann–de Lange syndrome;
- facial features;
Cornelia de Lange syndrome (CdLS) is a dominant disorder with classic severe forms and milder atypical variants. Central to making the diagnosis is identification of diagnostic facial features. With the recognition that patients with SMC1A and SMC3 mutations have milder, atypical features, we surveyed 65 dysmorphologists using facial photographs from 32 CdLS patients with the goals of (1) Illustrating examples of milder patients with SMC1A mutations and (2) Obtaining objective data to determine which facial features were useful and misleading in making a diagnosis of CdLS. Clinicians were surveyed whether the patient had CdLS or another diagnosis, the certainty of response and the clinical features used to support each response. Using only facial photographs, an average of 24 cases (75%) were accurately diagnosed per clinician. Correct diagnoses were made in 90% of classic CdLS and 87% of non-CdLS cases, however, only 54% of mild or variant CdLS were correctly diagnosed by respondents. We confirmed that CdLS is most accurately diagnosed in childhood and the diagnosis becomes increasingly difficult with age. This survey demonstrated that emphasis is placed on the eyebrows, nasal features, prominent upper lip and micrognathia. In addition, the presence of fuller, atypical eyebrows, a prominent nasal bridge and significant prognathism with age dissuaded survey takers from arriving at a diagnosis of CdLS in individuals with mild NIPBL and SMC1A mutations. This work underscores the difficulty in diagnosing patients with mild and variant CdLS and serves to objectively classify both useful and misleading features in the diagnosis of CdLS. © 2010 Wiley-Liss, Inc.