Emotional functioning among children with neurofibromatosis type 1 or Noonan syndrome

Abstract

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. K E Y W O R D Sanxiety, depression, emotional function, neurofibromatosis type 1, Noonan syndrome, RASopathies

Manic and Depressive Symptoms in Children Diagnosed with Noonan Syndrome

“…Another important finding is that 28% of our sample have anxious symptomatology, consistent with previous findings describing a high prevalence of anxiety traits and ADHD in children with NS when compared to the general population [19]. Several authors have reported that anxious symptoms are important predictors of future development of depressive disorders, and an increased risk of worse outcomes of depressive episodes in terms of greater depressive long term morbidity as well as an increased risk in suicidal behavior [44][45][46]59]. Indeed, several studies have reported a high prevalence of depressive disorders in adults diagnosed with NS [1,21,29], and a high prevalence of NS subjects have been reported to need an antidepressant treatment during adult ages [21].…”

“…Indeed, nearly a half (46%) of our cohort with NS shows at least a DESR profile (dysregulation profile or deficient emotional self-regulation), highlighting emotional dysregulation problems as a relatively common feature. This latter finding confirms the general clinical evidence that subjects with ADHD (with and without genetic syndromes) often show emotional dysregulation [37,39,[43][44][45][46], and raise questions on the psychopathological characterization and the future development of this unspecific clinical feature. Some authors have reported that a very severe dysregulation profile rated with CBCL-AAA is highly related with the progression to a full syndromic pediatric bipolar disorder, frequently associated with ADHD [57].…”

“…Considering the large amount of evidence of a high risk for depressive episodes in adults with NS, we hypothesized that there might be a continuity between the severe mood-dysregulation with subsyndromal depressive and (hypo)manic symptoms observed in childhood [15,[18][19][20]24,25,32,36,44], and the depressive episodes described in adults with NS. Longitudinal studies are needed to explore whether irritability and the DESR profile contribute to mood disorders in children with NS, and whether they have a predictive value of future development of a mood disorder in adult ages.…”

“…Our previous findings [43] also showed affective and behavioral dysregulation symptoms as measured using the CBCL-AAA profile in children diagnosed with RASopathies (mainly NS). Several studies underlined a strong overlap between the ADHD and anxious-depressive features among children diagnosed with RASopathies, mainly among NS subjects [44][45][46]. Despite that, little is known about the presence of mood and anxiety symptoms in individuals with NS.…”

Psychological characteristics of adult neurofibromatosis type 1 patients seeking elective surgery

“…For example, impairments in general cognitive/ executive function, learning and social skills, anxiety and depression are associated with NF1 [4][5][6]. This is more than a social myth that comes from appearance, because these impairments are caused by pathogenic variants in genes encoding the Ras-mitogenactivated protein kinase signaling pathway [18]. These neurological and emotional features have significant negative impacts on QOL [19,20].…”