Manic and Depressive Symptoms in Children Diagnosed with Noonan Syndrome

Abstract

Noonan syndrome (NS) is a dominant clinically variable and genetically heterogeneous developmental disorder caused by germ-line mutations encoding components of the Ras–MAPK signaling pathway. A few studies have investigated psychopathological features occurring in individuals with NS, although they were poorly analyzed. The aim of the present work is to investigate the psychopathological features in children and adolescents with NS focusing on depressive and hypo-manic symptoms. Thirty-seven subjects with molecularly confirmed diagnosis were systematically evaluated through a psychopathological assessment. In addition, an evaluation of the cognitive level was performed. Our analyses showed a high recurrence of attention deficit and hyperactivity disorder symptoms, emotional dysregulation, irritability, and anxiety symptomatology. The mean cognitive level was on the average. The present study provides new relevant information on psychopathological features in individuals with NS. The implications for clinicians are discussed including the monitoring of mood disorders in a clinical evolution.

Cognitive Phenotype and Psychopathology in Noonan Syndrome Spectrum Disorders through Various Ras/MAPK Pathway Associated Gene Variants

“…In adults, “only” a lower speed of information processing and social cognitive impairments have been demonstrated in case-control studies [ 10 , 11 ]. With respect to behavior and psychopathology, children with NSSDs tend to display more symptoms of attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) than do typically developing children, which is in line with deficits found in attention and social cognition [ 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 ]. A higher risk of internalizing problems has been repeatedly described for both juveniles [ 13 , 14 , 20 , 21 ] and adults [ 10 , 22 , 23 , 24 ].…”

Genetic conditions of short stature: A review of three classic examples

“…Psychological and psychosocial issues associated with NS may include increased clumsiness, stubbornness, and irritability and weaker social skills compared with unaffected siblings (1,97). Children with RASopathies, particularly NS, often display symptoms associated with attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), including inattention, poor impulse control, and hyperactivity, although they may not always meet the stringent criteria necessary for an official diagnosis (12,13,15,17,97). Language impairments are more frequent in children with NS and are associated with a higher risk of reading and spelling difficulties (98).…”

“…Those with NS may also experience poor body image, selfesteem issues, anxiety, and depression (1,17). It has been suggested that some of these social issues may be linked to poor verbal development (95).…”

“…It has been suggested that some of these social issues may be linked to poor verbal development (95). Even into adulthood, individuals with NS may have difficulty maintaining satisfying social relationships and may report low-to-moderate levels of overall life satisfaction (17).…”

“…Clinical neuropsychological evaluation of the cognitive, adaptive, and psychological domains of functioning should extend from childhood through the transition phase in individuals with NS (12). Adults with NS may also experience social and interpersonal issues, which can lead to anxiety, depression, and lower overall life satisfaction (1,17). Ideally, a multidisciplinary team composed of geneticists, cardiologists, endocrinologists, and behavioral and mental health experts will be involved in a coordinated transition.…”