Manic and Depressive Symptoms in Children Diagnosed with Noonan Syndrome.

Paolo Alfieri,Camilla Frattini,Stefano Vicari,Serena Licchelli,Rossella Capolino,Cristina Caciolo,Flavia Cirillo,Maria Cristina Digilio,Francesco Scibelli,Monia Trasolini,Maria Pia Casini,Giulia Serra,Adele D’Amico,Francesca Cumbo,Marco Tartaglia

doi:10.3390/brainsci11020233

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.

Highlights

Noonan syndrome (NS) is a clinically variable and genetically heterogeneous disorder affecting development and growth
PTPN11, seven carried mutations in SOS1, two in LZTR1, two in RAF1, and one subject was heterozygous for a mutation in RIT1
One subject carried a SHOC2 mutation, which underlies the Mazzanti syndrome, a phenotype clinically related to NS

Summary

Introduction

Noonan syndrome (NS) is a clinically variable and genetically heterogeneous disorder affecting development and growth. NS is considered as one of the most common non-chromosomal disorders affecting neurodevelopment. NS is caused by germ-line mutations in genes encoding components of the Ras–MAPK signaling pathway [4]. In approximately 50% of cases, it is caused by dominant mutations in PTPN11 [5]. Heterozygous activating mutations in SOS1, RAF1, and RIT1 represent relatively common events, while an increasing number of genes (e.g., NRAS, SOS2, RRAS2, and MRAS) have been reported to account for a relatively small proportion of cases [6,7,8,9]. In a significant proportion of patients with NS, loss-of-function (recessive form) or dominant negative (dominant form) mutations in LZTR1 have been reported

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