Perceived stress in caregivers of patients with RASopathies: Clinical implications, therapeutic adaptation strategies, and the role of psychological support in high-complexity care settings

Journal title QUADERNI DI PSICOTERAPIA COGNITIVA
Author/s Lucrezia Perri, Chiara Leoni, Daniela Pia Rosaria Chieffo
Publishing Year 2026 Issue 2025/56
Language Italian Pages 9 P. 76-84 File size 0 KB
DOI 10.3280/qpc56-2025oa21772
DOI is like a bar code for intellectual property: to have more infomation click here

View article Download Open Access article

FrancoAngeli is member of Publishers International Linking Association, Inc (PILA), a not-for-profit association which run the CrossRef service enabling links to and from online scholarly content.

The perceived stress of caregivers of patients with RASopathies represents a significant clinical challenge, particularly in complex settings such as hospitals, where the emotional and caregiving burden is intensified. The aim of this study was to assess parental stress levels in families of children with cardio-facio-cutaneous (CFC) syndrome and Costello syndrome (CS). The sample included 39 children (22 CFC, 17 CS) and 53 parents, who completed the Italian version of the Parenting Stress Index-Short Form. The results show that caregivers in the CFC group reported significantly higher levels of total stress and higher scores on the “Parental Distress”, “Parent-Child Dysfunctional Interaction”, and “Difficult Child” subscales compared with the CS group. A larger proportion of CFC parents had clinically relevant scores (≥85th percentile). Multivariate analysis, weighted for parental role, confirmed that
belonging to the CFC group was associated with an average increase of approximately 18-25 percentile points (p < 0.05) in perceived stress. The findings support the view that psychological support for caregivers is a key component of family-centered interventions, particularly in the presence of complex clinical conditions and prolonged hospitalizations, helping to reduce the emotional burden and improve the quality of life of both patients and their families.

Keywords: RASopathies;Parental stress;Parenting Stress Index (PSI-SF);Parent Training;High-complexity care settings

  1. Abidin R.R. (1995). Parenting Stress Index (PSI) manual (3rd ed.). Odessa: Psychological Assessment Resources.
  2. Aoki Y., Niihori T., Kawame H., et al. (2005). Germline mutations in HRAS cause Costello syndrome. Nature Genetics, 37(10): 1038-1040. DOI: 10.1038/ng1641
  3. Cohen J.A., Mannarino A.P. & Staron V.R. (2006). A pilot study of modified cognitive-behavioral therapy for childhood traumatic grief (CBT-CTG). Journal of the American Academy of Child & Adolescent Psychiatry, 45(12): 1465-1473. DOI: 10.1097/01.chi.0000237705.43260.2c
  4. Cousino M.K. & Hazen R.A. (2013). Parenting stress among caregivers of children with chronic illness: A systematic review. Journal of Pediatric Psychology, 38(8): 809-828. DOI: 10.1093/jpepsy/jst049
  5. Dentici M.L., Sarkozy A., Pantaleoni F. et al. (2009). Spectrum of MEK1 and MEK2 gene mutations in cardio-facio-cutaneous syndrome. European Journal of Human Genetics, 17, 733-740. DOI: 10.1038/ejhg.2008.256
  6. Forehand R. & Parent J. (2012). Behavioral parenting interventions for child disruptive behavior and anxiety: What’s different and what’s the same? Clinical Psychology Review, 32(7): 488-498. DOI: 10.1016/j.cpr.2012.10.010
  7. Gripp K.W., Lin A.E., Axelrad M. et al. (2019). Costello syndrome: Clinical phenotype, genotype, and management guidelines. American Journal of Medical Genetics A, 179(9): 1725-1744. DOI: 10.1002/ajmg.a.61270
  8. Hastings R.P. & Brown T. (2002). Behavior problems of children with autism, parental self-efficacy, and mental health. American Journal on Mental Retardation, 107(3): 222-232. DOI: 10.1352/0895-8017(2002)107<0222:BPOCWA>2.0.CO;2
  9. Hinojosa M.S., Hinojosa R., Fernandez-Baca D., Knapp C. & Thompson L.A. (2012). Parental strain, parental health, and community characteristics among children with attention deficit-hyperactivity disorder. Academic Pediatrics, 12(6): 502-508. DOI: 10.1016/j.acap.2012.06.009
  10. Istituto Superiore di Sanità – Epicentro (2022). Malattie rare: almeno 1 milione di persone in Italia. Disponibile su: www.epicentro.iss.it/ben/2022/3/malattie-rare-telefono-verde-2019-2021.
  11. Leoni C., Viscogliosi G., Tartaglia M., Aoki Y. & Zampino G. (2022). Multidisciplinary management of Costello syndrome: Current perspectives. Journal of Multidisciplinary Healthcare, 15, 1277-1296. DOI: 10.2147/JMDH.S291757
  12. Montanaro F.A.M., Alfieri P., Caciolo C., Cumbo F., Piga S., Tartaglia M., Licchelli S., Digilio M.C. & Vicari S. (2022). Neuropsychological features in RASopathies: A pilot study on parent training program involving families of children with Noonan syndrome. American Journal of Medical Genetics Part C: Seminars in Medical Genetics, 190(4): 510-519. DOI: 10.1002/ajmg.c.32025
  13. Niihori T., Aoki Y., Narumi Y. et al. (2006). Germline KRAS and BRAF mutations in cardio-facio-cutaneous syndrome. Nature Genetics, 38(3): 294-296. DOI: 10.1038/ng1749
  14. Perri L., Leoni C. et al. (2024). Parenting Stress Index in caregivers of individuals with Noonan syndrome and related conditions. American Journal of Medical Genetics B. DOI: 10.1002/ajmg.b.33009
  15. Rauen K.A. (2013). The RASopathies: An evolving molecular-genetic and clinical nosology. Cold Spring Harbor Perspectives in Medicine, 3(10): a009747. DOI: 10.1101/cshperspect.a009747
  16. Rauen K.A. (2023). “Cardiofaciocutaneous syndrome”. In: GeneReviews®. University of Washington.
  17. Rodriguez-Viciana P., Tetsu O., Tidyman W.E. et al. (2006). Germline mutations in MAPK pathway genes cause cardio-facio-cutaneous syndrome. Science, 311(5765): 1287-1290. DOI: 10.1126/science.1124642
  18. Scorrano G., David E., Calì E., Chimenz R., La Bella S., Di Ludovico A., Di Rosa G., Gitto E., Mankad K., Nardello R., Mangano G.D., Leoni C. & Ceravolo G. (2023). The cardiofaciocutaneous syndrome: From genetics to prognostic-therapeutic implications. Genes, 14(12), 2111. DOI: 10.3390/genes14122111
  19. Shilling V., Morris C., Thompson-Coon J., Okoumunne O., Rogers M. & Logan S. (2013). Peer support for parents of children with chronic disabling conditions: A systematic review. Developmental Medicine & Child Neurology, 55(7): 602-609. DOI: 10.1111/dmcn.12091
  20. Singer G.H.S., Ethridge B.L. & Aldana S.I. (2007). Primary and secondary effects of parenting and stress-management interventions for parents of children with developmental disabilities: A meta-analysis. MRDD Research Reviews, 13(4): 357-369. DOI: 10.1002/mrdd.20175
  21. Solomon D.T., Niec L.N. & Schoonover C.E. (2017). The impact of foster parent training on parenting skills and child disruptive behavior. Child Maltreatment, 22(1): 3-13. DOI: 10.1177/1077559516679514
  22. Stroud L., Green K., Bloomfield S., Cronje J. & Foxcroft C. (2016). Griffiths Scales of Child Development (third edition). Hogrefe.
  23. Woodman A.C. (2015). Parenting stress and child behavior problems within families of children with developmental disabilities: Transactional relations across 15 years. Research in Developmental Disabilities, 36: 264-276. DOI: 10.1016/j.ridd.2014.10.011
  24. Zenker M. (2022). Clinical overview on RASopathies. American Journal of Medical Genetics Part C, 190(3): 414-424. DOI: 10.1002/ajmg.c.32015

Lucrezia Perri, Chiara Leoni, Daniela Pia Rosaria Chieffo, Stress percepito nei caregiver di pazienti con RASopatie: implicazioni cliniche, strategie di adattamento terapeutico e ruolo del supporto psicologico nei contesti assistenziali ad alta complessità in "QUADERNI DI PSICOTERAPIA COGNITIVA" 56/2025, pp 76-84, DOI: 10.3280/qpc56-2025oa21772