Evidence map›Paper›PMID 40459753›Full record

ArticleEuropean child & adolescent psychiatry2025

Irritability in children with RASopathies, insights into emotional dysregulation and social impairment.

Yaffa Serur, Naomi Fuhrmann, Odeya Russo, Tamar Green

Abstract read
In one paragraph

Article in European child & adolescent psychiatry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

4 authors.

Yaffa SerurDivision of Interdisciplinary Brain Sciences, Department of Psychiatry and Behavioral Science, School of Medicine, Stanford University, 401 Quarry Road, Stanford, CA, 94305-5717, USA. yserur@stanford.edu.
Naomi FuhrmannDivision of Interdisciplinary Brain Sciences, Department of Psychiatry and Behavioral Science, School of Medicine, Stanford University, 401 Quarry Road, Stanford, CA, 94305-5717, USA.
Odeya RussoDivision of Interdisciplinary Brain Sciences, Department of Psychiatry and Behavioral Science, School of Medicine, Stanford University, 401 Quarry Road, Stanford, CA, 94305-5717, USA.
Tamar GreenDivision of Interdisciplinary Brain Sciences, Department of Psychiatry and Behavioral Science, School of Medicine, Stanford University, 401 Quarry Road, Stanford, CA, 94305-5717, USA.

Funding

Gaining insights: the effects of the RMK gain-of-function mutations on brain development and neurodevelopmental disordersR01HD108684 · NICHD · STANFORD UNIVERSITY · PI Tamar Green · 2022 to 2026
$3.0M
Ras/MAPK Mutations Effects on the Developing BrainK23HD090209 · NICHD · STANFORD UNIVERSITY · PI GREEN, TAMAR · 2018 to 2022
$837k
National Institute of Child Health and Human Development 123752K23NICHD NIH HHS K23 HD090209NICHD NIH HHS R01 HD108684
6 · The paper itself

Abstract

RASopathies, including Noonan Syndrome (NS) and Neurofibromatosis type 1 (NF1), are developmental disorders caused by germline mutations in genes of the RAS-mitogen-activated protein kinase pathway (RAS-MAPK). This study investigates irritability, a highly prevalent transdiagnostic construct, in children with NS and NF1 and the impact of RASopathy status on the associations between irritability, emotional dysregulation-related disorders, and social impairment. The sample comprises 174 children aged 4–17 (age mean = 9.49; 98 females), including 113 children with RASopathies (NS n = 85, NF1 n = 28) and 61 age-sex-matched typically developed (TD) children. We used parent proxy questionnaires (CBCL, SRS) to assess irritability, symptoms of ADHD, defiance, anxiety/depression, and social impairment while controlling for cognitive measures (IQ). Children with RASopathies exhibited higher irritability than TD children (mean difference = 1.09; p <.001). Children with NS showed a weaker association between irritability and ADHD symptoms compared to TD children (p =.032, ηp2 = 0.03) and a stronger association between irritability and social impairment compared to both TD (p =.033, ηp2 = 0.03) and NF1 groups (p =.009, ηp2 = 0.06). We present novel and clinically significant findings showing high irritability in children with NS and NF1. Our study provides syndrome-specific results, suggesting differences in the mechanisms involved in irritability, ADHD, and social processes. In essence, children with RASopathies showed a highly irritable profile associated with ADHD symptoms and social impairment, with a significantly stronger association between irritability and social processes in NS. Our results suggest that developing prevention and treatments targeting irritability can distinctly affect the trajectories of neurodevelopmental disorders in children with NS and NF1.

Indexed as

Affective SymptomsEmotional RegulationIrritable MoodNeurofibromatosis 1Noonan SyndromeAdolescentAttention Deficit Disorder with HyperactivityChildChild, PreschoolFemaleHumansMaleEmotional dysregulation-related disordersIrritabilityNeurofibromatosis type 1Noonan syndromeRASopathiesSocial impairment

Identifiers

PMID40459753
PMCPMC12335977

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.