Original article| Volume 22, ISSUE 1, P170-177, January 2018

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Psychopathological features in Noonan syndrome

Published:September 27, 2017DOI:


      • We identified behavioural and psychiatric features in NS and related Noonan like-disorders.
      • The prevalence of ADHD and anxiety in children with NS is significantly greater than in the general Italian juvenile population.
      • ADHD disorder is present in individuals carrying mutation on all three genes (PTPN11, SOS1, SHOC2).



      Noonan syndrome (NS) is an autosomal dominant disorder characterized by short stature, skeletal and haematological/lymphatic defects, distinctive facies, cryptorchidism, and a wide spectrum of congenital heart defects. Recurrent features also include variable cognitive deficits and behavioural problems. Recent research has been focused on the assessment of prevalence, age of onset and characterization of psychiatric features in this disorder. Herein, we evaluated the prevalence of attention deficit and hyperactivity disorder (ADHD), anxiety and depressive symptoms and syndromes in a cohort of individuals with clinical and molecular diagnosis of NS.


      The Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children Present and Lifetime version (K-SADS PL) has been used for the assessment of psychiatric disorders according to Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). Multidimensional Anxiety Scale for Children (MASC) and the Children's Depression Inventory (CDI) have been assessed for the evaluation of anxiety and depressive symptoms and syndromes, whereas Conners Teacher and Parent Rating Scales-long version (CRS-R) have been used to evaluate ADHD.


      The study included 27 individuals (67% males) with an average age of 10.4 years (range 6–18 years) receiving molecular diagnosis of NS or a clinically related condition, evaluated and treated at the Neuropsychiatric Unit of Children's Hospital Bambino Gesù and at the Center for Rare Diseases of Fondazione Policlinico Universitario Agostino Gemelli, in Rome. Twenty individuals showed mutations in PTPN11, five in SOS1 and two in SHOC2. The mean IQ was 94 (Standard Deviation = 17, min = 56, max = 130). Seventy percent of the individuals (n = 19; 95% Confidence Interval = 52–85%) showed ADHD features, with six individuals reaching DSM-IV-TR criteria for ADHD disorder, and thirteen showing subsyndromal traits. Symptoms or syndrome of anxiety were present in 37% of the cohort (n = 10; 95% Confidence Interval = 19–56%), with two individuals showing anxiety disorder and eight cases exhibiting subsyndromal traits.


      Our results show individuals with NS do present a very high risk to develop psychiatric disorders or symptoms during paediatric age. Based on these findings, preschool assessment of inattentive, hyperactivity/impulsivity and anxiety/depressive symptoms is recommended in order to plan a personalized treatment for psychological/psychiatric issues in affected individuals. Dedicated prospective studies are required to confirm the present data and better characterize the psychopathological profile in NS.



      ADHD (Attention Deficit and Hyperactivity Disorder), CDI (Children's Depression Inventory), CI (Confidence Interval), CRS-R (Conners Teacher and Parent Rating Scales-long version), DSM-IV-TR (Diagnostic and statistical manual of mental disorder 4th ed., text rev.), K-SADS PL (Schedule for Affective Disorders and Schizophrenia Present and Lifetime version), ID (intellectual disability), NS (Noonan syndrome), NS-ML (Noonan syndrome with multiple lentigines)
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