Executive functioning in adolescents and adults with Silver-Russell syndrome

PLoS One. 2023 Jan 20;18(1):e0279745. doi: 10.1371/journal.pone.0279745. eCollection 2023.

Abstract

Silver-Russell syndrome (SRS) is a rare imprinting disorder characterized by prenatal and postnatal growth retardation. The two principal causes of SRS are loss of methylation on chromosome 11p15 (11p15 LOM) and maternal uniparental disomy of chromosome 7 (UPD(7)mat). Knowledge of the neuropsychological profile of SRS remains sparse and incomplete even if several difficulties related to attention and learning have been reported both in the literature and by patients with SRS. These difficulties could be the result of troubles in different cognitive domains, but also of executive dysfunction. Nevertheless, executive functioning has never been investigated, even though executive functions play an essential role in psychological development, and are extensively involved in daily life. The present study explored the executive functioning of individuals with SRS due to UPD(7)mat or 11p15 LOM. A battery of executive tasks assessing cognitive flexibility, inhibitory control, and working memory, together with a task assessing sustained attention, was administered to 19 individuals with SRS (13-39 years) and 19 healthy controls. The Behavior Rating Inventory of Executive Function was also completed by the participants' families. The results showed that participants with SRS had similar performance (z-scores) to our controls, in a context of normal intellectual efficiency. Group comparisons with Bayesian statistics showed a single difference between the 11p15 LOM and control groups: the completion time for part A of the Trail Making Test appeared to be longer in the 11p15 LOM group than in the control group. However, at the clinical level, several participants with SRS had clinically significant scores on various measures of EFs. Thus, the cognitive phenotype of SRS did not appear to be characterized by executive dysfunction, but individuals with SRS could be at high risk of developing executive dysfunction or attention-deficit/hyperactivity disorder. These results provide new insights into the neuropsychological profile of individuals with SRS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bayes Theorem
  • DNA Methylation
  • Executive Function
  • Female
  • Genomic Imprinting
  • Humans
  • Methylation
  • Phenotype
  • Pregnancy
  • Silver-Russell Syndrome* / genetics
  • Uniparental Disomy

Grants and funding

Bretagne Atlantique Ambition, an endowment fund for research and innovation in Western France (http://www.baa-recherche.fr), financed the salary of MB's doctoral thesis (Agreement No. 150827). Bretagne Atlantique Ambition had no further role in study design, in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication.