Emotional functioning among children with neurofibromatosis type 1 or Noonan syndrome

Am J Med Genet A. 2019 Dec;179(12):2433-2446. doi: 10.1002/ajmg.a.61361. Epub 2019 Sep 30.


While neurofibromatosis type 1 (NF1) and Noonan syndrome (NS) are clinically distinct genetic syndromes, they have overlapping features because they are caused by pathogenic variants in genes encoding molecules within the Ras-mitogen-activated protein kinase signaling pathway. Increased risk for emotional and behavioral challenges has been reported in both children and adults with these syndromes. The current study examined parent-report and self-report measures of emotional functioning among children with NF1 and NS as compared to their unaffected siblings. Parents and children with NS (n = 39), NF1 (n = 39), and their siblings without a genetic condition (n = 32) completed well-validated clinical symptom rating scales. Results from parent questionnaires indicated greater symptomatology on scales measuring internalizing behaviors and symptoms of attention deficit hyperactivity disorder (ADHD) in both syndrome groups as compared with unaffected children. Frequency and severity of emotional and behavioral symptoms were remarkably similar across the two clinical groups. Symptoms of depression and anxiety were higher in children who were also rated as meeting symptom criteria for ADHD. While self-report ratings by children generally correlated with parent ratings, symptom severity was less pronounced. Among unaffected siblings, parent ratings indicated higher than expected levels of anxiety. Study findings may assist with guiding family-based interventions to address emotional challenges.

Keywords: Noonan syndrome; RASopathies; anxiety; depression; emotional function; neurofibromatosis type 1.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Age Factors
  • Child
  • Child Behavior
  • Emotions*
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Humans
  • Male
  • Neurofibromatosis 1 / diagnosis*
  • Neurofibromatosis 1 / genetics
  • Noonan Syndrome / diagnosis*
  • Noonan Syndrome / genetics
  • Parents
  • Phenotype
  • Self Report
  • Siblings
  • Surveys and Questionnaires