A new prognostic index of severity of intellectual disabilities in Cornelia de Lange syndrome

Am J Med Genet C Semin Med Genet. 2016 Jun;172(2):179-89. doi: 10.1002/ajmg.c.31494. Epub 2016 May 5.


Cornelia de Lange syndrome is a well-known multiple congenital anomalies/intellectual disability syndrome with genetic heterogeneity and wide clinical variability, regarding the severity of both the intellectual disabilities and the physical features, not completely explained by the genotype-phenotype correlations known to date. The aim of the study was the identification of prognostic features, ascertainable precociously in the patient's life, of a better intellectual outcome and the development of a new prognostic index of severity of intellectual disability in CdLS patients. In 66 italian CdLS patients aged 8 years or more, we evaluated the association of the degree of intellectual disability with various clinical parameters ascertainable before 6 months of life and with the molecular data by the application of cumulative regression logistic model. Based on these results and on the previously known genotype-phenotype correlations, we selected seven parameters to be used in a multivariate cumulative regression logistic model to develop a prognostic index of severity of intellectual disability. The probability of a mild ID increases with the reducing final score less than two, the probability of a severe ID increases with the increasing final score more than three. This prognostic index allows to define, precociously in the life of a baby, the probability of a better or worse intellectual outcome in CdLS patients. © 2016 Wiley Periodicals, Inc.

Keywords: Cornelia de Lange syndrome; clinical variability; intellectual outcome; prognostic index.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child
  • De Lange Syndrome / complications
  • De Lange Syndrome / diagnosis*
  • Genetic Association Studies
  • Genotype
  • Humans
  • Intellectual Disability / genetics*
  • Italy
  • Logistic Models
  • Prognosis
  • Severity of Illness Index*