How do people with neurofibromatosis type 1 (the forgotten victims) live? A grounded theory study

Abstract Background Neurofibromatosis type I (NF1) is a rare genetic disorder, associated with some physical symptoms including spots and tiny bumps on the skin, and internal organ involvement. People suffering from neurofibromatosis face various challenges in their daily lives. However, there is little understanding on how patients deal with neurofibromatosis. This study aimed to investigate the life challenges of patients with NF1. Methods This qualitative study was performed by implementing a grounded theory with the cooperation of the Society for Neurofibromatosis Patients over the course of 15 months in 2019 across 4 provinces in Iran. Twenty‐four patients with NF1 were interviewed. An analysis was performed using the constant comparative method. Findings The results of the analyses indicated that the major concern of the NF1 patients was feelings of failure and falling behind in life. In the face of failure in life in such a context, patients used the main strategy of “unsuccessful struggle to escape” the disease and its complications, which was represented itself in the forms of ‘hopelessness and impatience’, ‘suicidal thoughts and unsuccessful suicide attempts’, ‘isolation and seclusion’, ‘expressing complaints and grievances to God’, ‘hiding the disease’ and ‘hopelessness and refusing to receive care’. The implementation of such strategies helped patients reduce tension and achieve a temporary, though vulnerable and fragile, sense of relief and peace. Conclusion Given an unfavourable life condition, NF1 patients turned to a harmful passive strategy in the face of the challenges posed by the disease. Patient or Public Contribution Public contributors were active partners throughout, and co‐authored the paper.


| BACKGROUND
Neurofibromatosis type I (NF1), also known as Von Recklinghausen's disease, is an autosomal dominant disorder affecting the skin and the nervous system. There are no gender, racial or ethnic differences in terms of the occurrence of NF1. 1 NF1 is the most common type of neurofibromatosis, and affects 1 in 3500 people. 2,3 The exact prevalence of this disease has not been determined in Iran. Therefore, it is assumed that the prevalence rate of this genetic disorder in Iran is similar to the global prevalence of NF1. 4 The primary symptoms associated with NF1 include dermatologic complications in the form of 'café au lait' spots and patches. 4,5 NF1 can be associated with potential unpredictable and lifethreatening clinical presentations. 6 The cosmetic complications associated with neurofibromatosis and the resulting social isolation are the main factors for the depression that the patients experience.
It has been found that depression is quite common among patients suffering from NF1. The findings of previous studies have shown that the prevalences of depression and other psychiatric complications were higher in patients with NF1 compared to healthy adults. 7 Various physical, cognitive and social complications of NF1 can significantly reduce the quality of life of patients. 8 Knowledge of the personal experiences of patients suffering from NF1 is important for understanding their physical and mental (psychological) health and the social challenges that they face.
However, there has been a dearth of qualitative studies on the negative effects of NF1 on the lives and the mental health of adult patients. An impaired social network, concern over the unpredictability of the disease and concerns and worries in relation to cosmetic deformities have been previously reported as challenges experienced by patients with NF1. [9][10][11] The findings of previous studies conducted in other countries may not be helpful in understanding the experiences of NF1 patients in Iran as these experiences are affected by the geographical location, economic status, cultural background and lifestyle. Hence, the present study was designed to investigate the challenges in life faced by Iranian patients with NF1.

| METHODS
This qualitative study was based on a naturalistic research paradigm using the grounded theory.

| Participants
Twenty four adult male and female patients with NF1 from four different provinces of Iran participated in this qualitative study (Table 1). The inclusion criteria were as follows: (1) age older than 18 years, (2) confirmed diagnosis of NF1 according to the Society of Neurofibromatosis, (3) awareness of having the disease, (4) disease history of at least 6 months and (5) willingness to participate in the study by signing a formal consent form. As NF1 is a rare disease, the patients were introduced to the researcher by the Iranian Society of Neurofibromatosis. Purposeful sampling was implemented first, and preliminary interviews were conducted to formulate the primary concepts (themes) and hypotheses. The researcher then followed a theoretical sampling procedure to conduct further interviews with participants, and expand on the emerging concepts and diverging views. Interviews and data collection continued until theoretical data saturation was reached.

| Interview procedure
Semi-structured and unstructured interviews were conducted from September 2019 to May 2020. All interviews were audio-recorded. These concepts were used in the subsequent semi-structured interviews. Overall, 28 interviews were conducted with the 24 participants. Four participants were interviewed twice. The interview duration ranged between 45 and 110 min, with an average duration of 63 min. Theoretical saturation was achieved after the 24th interview. Finally, four more interviews were conducted to ensure that no new data could be obtained on each of the primary concepts.

| Data analysis
Analysis was performed using the constant comparative approach proposed by Corbin and Strauss. 12 The five steps of the grounded theory were used for data analysis. These steps include open coding, developing concepts in terms of their properties and dimensions, context analysis, process analysis and integrating categories. In addition, to fulfil the 10 criteria proposed by Corbin and Strauss, 12 the researcher used the techniques based on the four criteria of Lincoln and Guba to confirm and ensure the accuracy and strength of the study findings. 12,13 Max QDA software was used for data analysis.

| RESULTS
The analysis of the collected data from the first and second steps yielded 1492 codes in context, 57 subcategories and 10 categories or main concepts (themes). A thorough examination of these concepts and findings indicated that the main concern of the patients was 'failure and falling behind in their lives'.

| Main concern: Failure and falling behind in life
The concept 'failure and falling behind in life' was found to be the main concern and challenge that NF1 patients faced. This concept was defined as a disturbing, uncomfortable feeling experienced by A variety of factors were reported to negatively influence marriage.
Thus, NF1 patients usually experienced failed marriages.
In terms of marriage, a 26-year-old male patient in the present study stated that: Nobody wants to marry an NF1 patient. Even if one starts a relationship with an NF1 patient, as soon as he or she comes to know about the disease, he or she will definitely reject the marriage proposal. (Participant 9) When NF1 patients pursued an employment opportunity, they felt that employers generally refused to give them a job position due to changes in their appearance. As appearance was regarded as an important factor for employers in their decision-making while processing job applications. Due to their appearance, NF1 patients reported that they mostly faced a negative outcome when they applied for a job. In this respect, one of the participants stated that: The other day I went to some place to apply for a se-

| Processes
In response to the feeling of failure and falling behind in life (main concern) in the context mentioned above, patients with NF1 commonly used the following strategies: 'being impatient and hopeless', 'thinking of suicide, and unsuccessful suicide attempts', 'isolation and seclusion', 'complaining to God', 'covering and hiding their condition' and refusing to receive care. NF1 patients tried to hide their symptoms and complications in different ways to avoid social stigma and the consequences, including unfair and wrong judgements of people of their genetic disorder.
In this respect, a 42-year-old single participant reported that she wore more clothes to hide her complications: patients were forced to use some ineffective approaches, including hiding their disease from others, seeking isolation and separation, complaining to God, feeling impatient and hopeless and refusing to receive care. In some cases, they contemplated suicide, and even made unsuccessful suicide attempts.
Although the implementation of such ineffective passive approaches sometimes helped NF1 patients achieve relative peace, this feeling of peace and calmness was so fragile that it was disrupted by the persisting complications of the condition and its negative effects.
As a result, the feeling of failure experienced was intensified in NF1 patients. Over time, NF1 patients lost their ability to tolerate the disease; thus, they considered other approaches that they believed to be more effective in helping them achieve peace in life. Thus, they started contemplating suicide as a way to escape the disease and to achieve eternal peace by ending their lives.
Therefore, this process of action and reaction, from the feelings of failure in life, to a relatively fragile sense of peace, was indicative of the 'unsuccessful struggle to escape' in response to the feelings of failure and falling behind in life (Figure 1).

| DISCUSSION
The primary purpose of the present study was to explore the experiences of patients living with NF1. Data analysis revealed that the life of NF1 patients and their response to the feelings of failure and falling behind in life can be best described as 'an unsuccessful struggle to escape'.
Feelings of failure and falling behind in life were determined to be the main concern and worry among NF1 patients. These feelings contributed towards failure in marriage, employment and school achieve- In a study conducted by Farhi et al., 19 it was found that NF1 couples who planned to have children underwent diagnostic interventions before the birth of their children so that It was found that NF1 couples who intended to have a child, requested for the prenatal diagnostic procedures, with the aim of preventing the passing of the defective gene to the child.
Moreover, it was observed that none of the couples were willing to have more children again without medical interventions. 19 The participants in the present study considered neurofibromatosis as a limiting condition. In a systematic qualitative review, Von de Lippe et al. 20  In this respect, the study by Dalgard et al. 21 on the mental stress caused by skin disorders suggested that aggression, social rejection and other social problems may intensify negative feelings, incompatible thought processes (the feeling of deficit), negative self-perception (reduced self-esteem and having a negative physical image of oneself) and negative behavioural patterns (too much social isolation). It is not a coincidence that sociopsychological complications such as depression, suicidal thoughts and anxiety are widespread among these patients. 21

| CONCLUSIONS
The findings of the present study indicated that although neurofibromatosis is mainly a physical genetic disorder, patients suffering from this disease face painful emotional and social experiences and suffering due to the cosmetic deformities caused by the disease. Currently, it is impossible for the majority of NF1 patients to undergo cosmetic surgeries. Hence, it is advisable to provide psychiatric and psychological support to these patients. In this way, the patients may learn coping skills that can help them cope with the mental suffering that they experience.

ACKNOWLEDGEMENT
This study was supported by the Deputy of Research and Technology of Golestan University of Medical Sciences.

CONFLICT OF INTERESTS
The authors declare that there are no conflict of interests.

ETHICS STATEMENT
All important ethical considerations were followed during the course of the present study, including obtaining formal permits from the authorities, introducing researchers to the participants, informing the participants about the objectives of the study and the length of F I G U R E 1 Theoretical statement: 'unsuccessful struggle to escape' as the approach that participants implemented to deal with neurofibromatosis FOJI ET AL.
interviews, obtaining formal written consent from all participants before the start of the study, obtaining permission to record interviews from the participants, letting the participants know that they could leave the study at any stage at their own volition and assuring the participants of the anonymity of their personal information and confidentiality of their data.

DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.