Facial diagnosis of mild and variant CdLS: Insights from a dysmorphologist survey

Sarika Rohatgi, Dinah Clark, Antonie D. Kline, Laird G. Jackson, Juan Pie, Victoria Siu, Feliciano J. Ramos, Ian D. Krantz, Matthew A. Deardorff

Research output: Contribution to journalArticlepeer-review

55 Scopus citations

Abstract

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 havemilder, 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 inmaking 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 variantCdLS 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 andmicrognathia. In addition, the presence of fuller, atypical eyebrows, a prominent nasal bridge and significant prognathismwith age dissuaded survey takers fromarriving 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.

Original languageEnglish (US)
Pages (from-to)1641-1653
Number of pages13
JournalAmerican Journal of Medical Genetics, Part A
Volume152
Issue number7
DOIs
StatePublished - Jul 2010
Externally publishedYes

Keywords

  • Brachmann-de Lange syndrome
  • Cornelia de Lange syndrome
  • Dysmorphology
  • Facial features
  • Facies
  • Mild
  • NIPBL
  • SMC1
  • SMC1A
  • SMC1L1
  • SMC3
  • Severe
  • Survey

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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