This mixed methods study examined mental health concerns and alienation among U.S. adults with neurofibromatosis type 1 (NF1) and parents of children with NF1. Qualitative interviews with six adult patients and six parents revealed 14 mental health triggers related to NF1 symptoms and care. Alienation was identified as a focal response to triggers during thematic analysis, and participants shared desired resources to cope with alienation and navigate care. A follow-up survey with 313 participants confirmed these triggers were commonly experienced. Survey respondents facing more triggers experienced greater alienation (Pearson’s r = 0.513 for patients, r = 0.396 for parents, p < 0.0001) and lower flourishing (Pearson’s r = −0.378 for patients, r = −0.371 for parents, p < 0.0001). Multiple linear regression accounting for sociodemographics confirmed these relationships as significant (p < 0.01). Targeting triggers of alienation requires greater development of educational, emotional, and social support resources; provider awareness and engagement in offering these supports; and promoting positive online content about living with NF1.
AghaeiAHerranKFanaeiSA, et al. (2024) Lived experiences of neurofibromatosis type 1 patients: Social life, stigma, and intervention strategies. Journal of Health Psychology29(8): 811–824. https://doi.org/10.1177/13591053231208619
2.
ArmitageSParkinsonMHalliganS, et al. (2020) Mothers’ experiences of having an adolescent child with depression: An interpretative phenomenological analysis. Journal of Child and Family Studies29: 1617–1629. https://doi.org/10.1007/s10826-020-01705-5
3.
BarkeJCoadJHarcourtD (2016) Parents’ experiences of caring for a young person with neurofibromatosis type 1 (NF1): A qualitative study. Journal of Community Genetics7(1): 33–39. https://doi.org/10.1007/s12687-015-0247-z
4.
BellampalliSSKhannaR (2019) Towards a neurobiological understanding of pain in neurofibromatosis type 1: Mechanisms and implications for treatment. Pain160: 1007–1018. https://doi.org/10.1097/j.pain.0000000000001486
5.
BicudoNPGermanoCMRde MoraesRT, et al. (2024) Association of sociodemographic and clinical factors with the quality of life of Brazilian individuals with Neurofibromatosis type 1: a cross-sectional study. Anais Brasileiros de Dermatologia99(4): 520–526. https://doi.org/10.1016/j.abd.2023.08.011
6.
BoettcherJBoettcherMWiegand-GrefeS, et al. (2021) Being the pillar for children with rare diseases-A systematic review on parental quality of life. International Journal of Environmental Research and Public Health18(9): 4993. https://doi.org/10.3390/ijerph18094993
7.
BogartKHemmeschABarnesE, et al. (2022) Healthcare access, satisfaction, and health-related quality of life among children and adults with rare diseases. Orphanet Journal of Rare Diseases17(1): 196. https://doi.org/10.1186/s13023-022-02343-4
8.
BrarKSTrivediCKaurN, et al. (2023) Prevalence of psychiatric comorbidities in patients with neurofibromatosis. Primary Care Companion For CNS Disorders25(5): 23m03514. https://doi.org/10.4088/PCC.23m03514
9.
BudychKHelmsTMSchultzC (2012) How do patients with rare diseases experience the medical encounter? Exploring role behavior and its impact on patient-physician interaction. Health Policy105: 154–164. https://doi.org/10.1016/j.healthpol.2012.02.018
10.
CerezoMVSoria-ReyesLMAlarcónR, et al. (2024) The Flourishing Scale: Psychometric properties in breast cancer patients. Integrative Cancer Therapies23: 15347354241249935. https://doi.org/10.1177/15347354241249935
11.
Cieza RiveraAMLobato FuertesCFernández-VillaT, et al. (2024) Impact of neurofibromatosis type 1 on quality of life using the Skindex-29 questionnaire quality of life in NF1. Orphanet Journal of Rare Diseases19: 85. https://doi.org/10.1186/s13023-024-03078-0
CohenJSLevyHPSloanJ, et al. (2015) Depression among adults with neurofibromatosis type 1: Prevalence and impact on quality of life. Clinical Genetics88: 425–430. https://doi.org/10.1111/cge.12551
DienerEWirtzDTovW, et al. (2010) New well-being measures: Short scales to assess flourishing and positive and negative feelings. Social Indicators Research97: 143–156. https://doi.org/10.1007/s11205-009-9493-y
16.
FojiSMohammadiESanagooA, et al. (2021) The patients’ experiences of burden of neurofibromatosis: a qualitative study. Iranian Journal of Nursing and Midwifery Research26(4): 342–348. https://doi.org/10.4103/ijnmr.ijnmr_178_20
17.
FojiSMohammadiESanagooA, et al. (2022) How do people with neurofibromatosis type 1 (the forgotten victims) live? A grounded theory study. Health Expectations25(2): 659–666. https://doi.org/10.1111/hex.13413
18.
GaoZLiSBaiX (2025) Social alienation and related factors in patients with head and neck tumors undergoing radiotherapy: A cross-sectional study. BMC Nursing24(1): 275. https://doi.org/10.1186/s12912-025-02932-1
19.
Gómez-ZúñigaBPulido MoyanoRPousada FernándezM, et al. (2019) The experience of parents of children with rare diseases when communicating with healthcare professionals: Towards an integrative theory of trust. Orphanet Journal of Rare Diseases14: 159. https://doi.org/10.1186/s13023-019-1134-1
20.
Hamoy-JimenezGKimRSuppiahS, et al. (2020) Qu ality of life in patients with neurofibromatosis type 1 and 2 in Canada. Neuro-oncology advances2(Suppl 1): i141–i149. https://doi.org/10.1093/noajnl/vdaa003
21.
HarrisPATaylorRThielkeR, et al. (2009) Research electronic data capture (REDCap)–a metadata-driven methodology and workflow process for providing translational research informatics support. Journal of Biomedical Informatics42: 377–381. https://doi.org/10.1016/j.jbi.2008.08.010
22.
HemmeschARBogartKRBarnesE (2025) “Lack” and “Finally”: A qualitative analysis of barriers and facilitators in rare disease healthcare’. International Journal of Environmental Research and Public Health22(1): 117. https://doi.org/10.3390/ijerph22010117
23.
HuYHeYLiuX, et al. (2025) Factors associated with social alienation in cancer patients: A structural equation modeling approach. Frontiers in Psychology16: 1721305. https://doi.org/10.3389/fpsyg.2025.1721305
24.
KaczorowskiJASmithTFDahlquistJ, et al. (2026) Parental adjustment to child neurofibromatosis 1: The role of long-term uncertainty. Journal of Pediatric Health Care40(1): 44–55. https://doi.org/10.1016/j.pedhc.2025.09.016
25.
KenborgLFrederiksenLEGalanakisM, et al. (2023) Employment, occupation, and income in adults with neurofibromatosis 1 in Denmark: A population- and register-based cohort study. Orphanet Journal of Rare Diseases18: 346. https://doi.org/10.1186/s13023-023-02965-2
26.
KillingsworthMA (2021) Experienced well-being rises with income, even above $75,000 per year. Proceedings of the National Academy of Sciences118: e2016976118. https://doi.org/10.1073/pnas.2016976118
27.
KrömekeAShaniM (2025) Flourishing in life in patients with inflammatory bowel disease: The role of illness identity and health-related quality of life. Journal of Health Psychology30(5): 1089–1103. https://doi.org/10.1177/13591053241260288
28.
MartinSStruemphKLPobleteA, et al. (2018) An internet support group for parents of children with neurofibromatosis type 1: A qualitative analysis. Journal of Community Genetics9(3): 327–334. https://doi.org/10.1007/s12687-018-0360-x
MeaseCFermaglichLJJacklerK, et al. (2024) Determining commonalities in the experiences of patients with rare diseases: A qualitative analysis of US Food and Drug Administration patient engagement sessions. Patient17: 25–37. https://doi.org/10.1007/s40271-023-00648-5
31.
MerkerVLDaiARadtkeHB, et al. (2018) Increasing access to specialty care for rare diseases: A case study using a foundation sponsored clinic network for patients with neurofibromatosis 1, neurofibromatosis 2, and schwannomatosis. BMC Health Services Research18: 668. https://doi.org/10.1186/s12913-018-3471-5
32.
MillerDTFreedenbergDSchorryE, et al. (2019) Health supervision for children with neurofibromatosis type 1. Pediatrics143: e20190660. https://doi.org/10.1542/peds.2019-0660
33.
PereraMJMeadeMADiPonioL (2018) Use and psychometric properties of the flourishing scale among adults with spinal cord injury. Rehabilitation Psychology63(2): 250–257. https://doi.org/10.1037/rep0000184
Ramírez-MaestreCCorreaMRivasT, et al. (2017) ‘Psychometric characteristics of the flourishing scale-Spanish version (FS-SV). The factorial structure in two samples: Students and patients with chronic pain’. Personality and Individual Differences117: 30–36. https://doi.org/10.1016/j.paid.2017.05.035
RayceSBKreinerSDamsgaardMT, et al. (2017) Measurement of alienation among adolescents: Construct validity of three scales on powerlessness, meaninglessness and social isolation. Journal of Patient-Reported Outcomes2: 14. https://doi.org/10.1186/s41687-018-0040-y
38.
RietmanABvan HeldenHBothPH, et al. (2018) Worries and needs of adults and parents of adults with neurofibromatosis type 1. American Journal of Medical Genetics Part A176: 1150–1160. https://doi.org/10.1002/ajmg.a.38680
39.
RingM (2025) An integrative approach to HPA axis dysfunction: From recognition to recovery. American Journal of Medicine138(10): 1451–1463. https://doi.org/10.1016/j.amjmed.2025.05.044
SeidlinMHolzmanRKnightP, et al. (2017) Characterization and utilization of an international neurofibromatosis web-based, patient-entered registry: An observational study. PLoS One12: e0178639. https://doi.org/10.1371/journal.pone.0178639
42.
StapleyEMidgleyNTargetM (2016) The experience of being the parent of an adolescent with a diagnosis of depression. Journal of Child and Family Studies25: 618–630. https://doi.org/10.1007/s10826-015-0237-0
43.
StewartDRKorfBRNathansonKL, et al. (2018) Care of adults with neurofibromatosis type 1: a clinical practice resource of the American College of Medical Genetics and Genomics (ACMG). Genetics in Medicine20: 671–682. https://doi.org/10.1038/gim.2018.28
44.
Thompson BurdineJThorneSSandhuG (2021) Interpretive description: a flexible qualitative methodology for medical education research. Medical Education55: 336–343. https://doi.org/10.1111/medu.14380
45.
von der LippeCDiesenPSFeragenKB (2017) living with a rare disorder: A systematic review of the qualitative literature. Molecular Genetics & Genomic Medicine5(6): 758–773. https://doi.org/10.1002/mgg3.315
46.
von der LippeCNetelandIFeragenKB (2022) Children with a rare congenital genetic disorder: A systematic review of parent experiences. Orphanet Journal of Rare Diseases17: 375. https://doi.org/10.1186/s13023-022-02525-0
47.
WangKEVranceanuAMLesterEG (2023) Resiliency outcomes after participation in an asynchronous web-based platform for adults with neurofibromatosis: The NF-Web study. PLoS One18(12): e0295546. https://doi.org/10.1371/journal.pone.0295546
48.
WangQGuJLinZ, et al. (2025) Social alienation in patients with inflammatory bowel diseases: A latent profile analysis. International Journal of Nursing Science12(4): 335–343. https://doi.org/10.1016/j.ijnss.2025.06.007
49.
WittSSchuettKWiegand-GrefeS, et al. (2023) Living with a rare disease - experiences and needs in pediatric patients and their parents. Orphanet Journal of Rare Diseases18: 242. https://doi.org/10.1186/s13023-023-02837-9
50.
WuYLiuJFornahL, et al. (2025) The effect of social alienation on stigma among stroke inpatients in China: A cross-sectional study. BMC Public Health25: 3580. https://doi.org/10.1186/s12889-025-25009-9
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
