Behavioral profile in RASopathies.
Here, we describe neurobehavioral features in patients with RASopathies (i.e., Noonan syndrome, LEOPARD syndrome, Costello syndrome, and cardiofaciocutaneous syndrome), developmental disorders caused by mutations in genes coding transducers participating in the RAS-MAPK signaling cascade. Parents of 70 individuals with a RASopathy were asked to fill out the following questionnaires: Child Behavior Checklist (CBCL), Social Communication Questionnaire version lifetime (SCQ-L), and Modified Checklist for Autism in toddlers (M-CHAT). Data analysis indicated high rates of internalizing (37%) and externalizing problems (31%) on CBCL. Scores over the cut-off were documented in 64% of patients with cardiofaciocutaneous syndrome, 44% with Costello syndrome, and 12% with Noonan syndrome on SCQ-L/M-CHAT. Our findings indicate that mutations promoting dysregulation of the RAS-MAPK cascade mark an increased psychopathological risk and highlight that autistic-like behavior could be underdiagnosed in patients with RASopathies.
Dipartimento di Neuroscienze, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
Paolo
P
Alfieri
Giorgia
G
Piccini
Cristina
C
Caciolo
Francesca
F
Perrino
Maria Luigia
ML
Gambardella
Maria
M
Mallardi
Laura
L
Cesarini
Chiara
C
Leoni
Daniela
D
Leone
Chiara
C
Fossati
Angelo
A
Selicorni
Maria Cristina
MC
Digilio
Marco
M
Tartaglia
Eugenio
E
Mercuri
Giuseppe
G
Zampino
Stefano
S
Vicari
D000293:Adolescent; D000328:Adult; D001321:Autistic Disorder / Q000201:enzymology / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D056685:Costello Syndrome / Q000201:enzymology / Q000235:genetics; D002658:Developmental Disabilities / Q000201:enzymology / Q000235:genetics; D004476:Ectodermal Dysplasia / Q000201:enzymology / Q000235:genetics; D019066:Facies; D005183:Failure to Thrive / Q000201:enzymology / Q000235:genetics; D005260:Female; D006330:Heart Defects, Congenital / Q000201:enzymology / Q000235:genetics; D006801:Humans; D044542:LEOPARD Syndrome / Q000201:enzymology / Q000235:genetics; D020935:MAP Kinase Signaling System / Q000235:genetics*; D008297:Male; D001523:Mental Disorders / Q000201:enzymology* / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D009634:Noonan Syndrome / Q000201:enzymology / Q000235:genetics; D055815:Young Adult; D018631:ras Proteins / Q000235:genetics*
D018631:ras Proteins
Costello syndrome; LEOPARD syndrome; Noonan syndrome; Noonan-like syndrome with loose anagen hair; RAS/MAPK cascade; behavior; cardiofaciocutaneous syndrome; genotype-phenotype correlation analyses