Neurofibromatsis type 1 (NF1)

With a prevalence of 1 in 3,000, NF1 is one of the most widespread autosomal dominant diseases in the world. One way of giving an idea of its pervasiveness is to point out that it occurs almost as often as cystic fibrosis (1 in 3,500) [17]. The disease predisposes sufferers to a high risk of both benign and malignant tumours [18]. The diagnostic criteria for NF1 are well known (see Table 1). Since the NF1 gene is expressed in all of the body's cells, its clinical manifestations (Table 1) can be cutaneous, skeletal, ophthalmological, and neurological [19]. NF1 can give rise to, among other things, serious esthetic problems (see Figure 2), learning difficulties, cognitive deficits, and psychosocial problems, which in turn are frequently associated with academic difficulties (see Table 1) [20], [21], [22], [23], [24].

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Figure 2. A woman who suffers from NF1.

(Photo: Marie-Soleil Lemay-Couture.).

https://doi.org/10.1371/journal.pone.0016409.g002

Proteus syndrome

Unlike NF1, Proteus syndrome is an extremely rare genetic condition, with only 205 recently published cases worldwide, of which only 97 satisfy the diagnostic criteria issued by the NIH in 1998 [15]. The causal mutation seems to occur in a consistently sporadic manner and the subsequent syndrome manifests itself in a mosaic pattern [15], [25]. Contrary to what is the case with NF, no specific genetic mutation has been identified for Proteus syndrome [15]. Proteus syndrome manifests as the excessive and unbalanced growth of multiple tissues and is also characterized by conjunctive tissue calcifications and narrowing and lengthening of long bones [15].

Initial methodology

For our study on intergenerational dialogue between parents and children with neurofibromatosis, our study design comprises three classical ethnographic investigative methods: 1) critical and comparative analysis of the literature; 2) participant observation; and 3) semi-structured interviews [26].

The emergent phenomenon

Since the presentations we made related to diverse aspects of NF1, people were inclined to speak to us spontaneously about what they were experiencing in connection with the disease. Thus during the participation observation process many NF1 patients or parents of children with NF1 told us of the extent to which the identification of NF1 with the disease of Joseph Merrick, the “elephant man”, had impacted on their lives both medically and psychosocially. This phenomenon was not among the themes we had originally planned to explore. However, in view of its ethical and clinical significance, this emergent issue required its own analysis. For this reason, we undertook an exploratory study aiming to: 1) document the persistence and extent of this fallacy; 2) identify certain critical factors that contribute to its persistence; and 3) evaluate its impact on the health and well being of individuals with NF1 and their family members.

Subsequent participant observation.

Once association members had told us that they continued to suffer from the confusion between NF1 and the disease Joseph Merrick had, we were sensitized to the suffering created by this situation. As of 2008 we began doing poster presentations to explain the difference between the two diseases at regional, national, and international scientific events (see Table 2). It was at this time that we also decided to gather the comments made by physicians and students who stopped at our poster presentations to discuss how they themselves or others whom they knew had fallen prey to the confusion between NF1 and Proteus syndrome.

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Table 2. Scientific Events at Which Presentations Were Made on Psychosocial and Ethical Issues Surrounding Neurofibromatosis.

https://doi.org/10.1371/journal.pone.0016409.t002

From that point on, we noted such comments in our field journals. As was mentioned above in connection with participant observation, since we were engaging in a process of observation, we did not collate any sociodemographic data about the people we spoke with. In any case, these data would not have been useful in the context of an exploratory study which had as one of its aims to learn whether the confusion in question persists among physicians and medical students and if so, why. We were not seeking to learn the frequency of this phenomenon in the target population. The kind of study with which such knowledge could be obtained can only be conducted once the problem has been identified, which is the scientific purpose served by exploratory studies.

NF1 and Proteus syndrome in the scientific literature

The scientific literature we reviewed and analyzed consisted of 26 articles on NF1 that used the words “elephant man”. Of these, as expected, all those dating form 1909 to 1986 said that Joseph Merrick suffered from NF1 [27], [28], [29]. After 1986, some authors persisted in the confusion. Hostamisligil and Seward actually question Tibbles and Cohen's diagnosis [30], [31], [32]. But for the most part, the scientific articles published later than 1986 no longer perpetrate the confusion [1], [3], [4], [16], [33], with three of them explicitly condemning it [1], [16], [34].

The confusion between NF1 and the “elephant man's” disease as found in print and online news media

In 1988, two years following the publication of Tibbles and Cohen's findings [7], the American newsmagazine Newsweek reported, in a brief news item called “What the Elephant Man really had”, that Joseph Merrick had not suffered from NF1 [35]. Despite this emergence of the information into the news media, numerous American newspapers went on associating NF1 with Joseph Merrick, the “elephant man” [36], [37], [38], [39], [40]. In response, in a letter to the editor that appeared in the New York Times in 1989, Joan Rudd Engel, a past president of the National Neurofibromatosis Foundation, explained how distressing this confusion could be to NF1 patients: “As brave and inspiring as [Joseph Merrick] has proved to be, the identification with him for the many with neurofibromatosis proved frightening and painful to them and was also inaccurate. It is in the interest of the many, many thousands of people with neurofibromatosis to see further comparison with the Elephant Man ended.” [41].

A decade later, American anthropologist Joan Ablon was the first researcher to decry the continued association of NF1 with the “elephant man's” disease in the media [1]. Nevertheless, the confusion did not cease. For example, when the first partial face transplant was performed in France in 2007, French newspapers [42], [43], [44] and some American [45] and Canadian [46] media outlets identified the patient's disease, which was in reality NF1, with Joseph Merrick's condition. Passages in the French media include “The patient suffered from von Recklinghausen's disease [an alternate name for NF1], an incurable disease that disfigures the face, as in the case of the hero of the movie The Elephant Man.” [43] The only media outlet to correct the misrepresentation was ABC News, which later reported that Joseph Merrick had not had NF1 but Proteus syndrome [47]. Media items discussing that face transplant since then have continued to identify NF1 with the “elephant man's” disease [48], [49], [50], [51]. As of 2008, the confusion between NF1 and Joseph Merrick's condition could still be found on Wikipedia, and as of July 2009 the Dictionary.com entry for the term “elephant man's disease” stated that it is NF1 and that it is so called because Joseph Merrick suffered from it [52].

The confusion between NF1 and Joseph Merrick's disease in the medical world

Even though the clinical differences between NF1 and Proteus syndrome are known, and despite the diagnostic methods available nowadays, the confusion persists not just in press representations but also in those of physicians. A few of our informants' stories of their experiences will suffice to illustrate this. For instance: “During dinner with friends, the conversation came around to the fact that my nephew had just been diagnosed with NF. A doctor who was present told me it was what the “elephant man” had had” (Érika, aunt of a child with NF1, Field Notes, 2008). (In order not to weigh down the text, we only quote one interview excerpt for each of the points raised by the study subjects. But the excerpts have been chosen with a view to reflecting the perspective of the largest possible number of people.) A comment of this kind provokes great anxiety and raises many questions: In this informant's place, one might wonder, “Do his parents know? Should I tell them – and what can I tell them? Will my nephew be able to go to school and take part in sports? What will he look like?” In confirmation of this, an informant who is a physician well informed about the difference between the two diseases expressed dismay at the fact that “so much ignorance exists around the subject of NF1” (Paul, physician, Field Notes, 2008).

In a clinical context, given the hierarchical relationship between physicians and patients, the association between NF1 and Proteus syndrome can have important psychological and medical repercussions. One patient told us the following in explaining that she was told more than once that she has the “elephant man's” disease: “The first time was when I was 15. The first neurologist who followed me told me I had the ‘elephant man's’ disease. Even the family physician who followed me between ages 15 to 25 often said to me, ‘Don't forget you have the ‘elephant man's’ disease, you could end up looking like him’. I didn't find this funny. The only thing he knew about the disease was what you could find in outdated medical encyclopedias. I don't resent him for this, though. It's thanks to him that I was diagnosed” (Kathy, woman with NF1, Field Notes, 2009). Another informant told us, “Hearing a doctor tell you in the ER (Emergency Room) that your child has the ‘elephant man's’ disease is traumatic” (Joyce, mother of a child with NF, Field Notes, 2008).

It is usually from their associations or from specialists familiar with NF1 that patients learn they don't have the condition from which Joseph Merrick suffered. Sometimes patients or family members have to inform physicians of this: “I actually had to explain to [the doctor] the difference between NF1 and Proteus syndrome. That was so very frustrating to hear that from a doctor in 2008” (Joyce, woman with NF1, Field Notes, 2009). Testimony to this effect from our informants confirms what Radtke et al. wrote in 2006: “Many families continue to be misinformed that NF1 is the ‘Elephant Man Disease’.” [16].

Since many physicians currently practicing were trained before the publication of Tibbles and Cohen's article in 1986, we can expect the confusion between NF1 and Proteus syndrome to continue for some years. During our poster presentations, many physicians we spoke to made comments like that of Georges: “When I was a resident, we were taught that Joseph Merrick suffered from NF1” (Georges, MD, PhD, Field Notes, 2008). Medical students also often made comments about NF1 like this one: “Hey, I know about that disease! It's the disease the ‘elephant man’ had; we talked about it in class” (Joan, medical student, Field Notes, 2009). Finally, Stedman's Medical Dictionary provides two definitions of “elephant man's disease”, one being that it is a synonym for Proteus syndrome and the other that it is a colloquial way of referring to NF1 [53].

A final point is that some physicians actually view the confusion as yielding benefits in the form of publicity for NF1: “If it brings NF1 to the attention of people around the world and makes it clear that it's a serious disease, that's a good thing” (John, MD, PhD, Field Notes, 2008). People who live with NF1 do not take this view. “We've been fighting for years to put an end to this confusion…. All it does is reinforce prejudices about the disease and intensify the sufferings of patients and their family members” (Gloria, mother of a child with NF1, Field Notes, 2007).

The impact of the confusion between NF1 and Proteus syndrome on the health and well being of individuals with NF1 and their family members

As we have seen, some reference sources, past medical training, and the print and online news media have all contributed to the persistence of the association between NF1 and the disease of Joseph Merrick in representations by the general public and health professionals. The viewpoint of patients and their family members is that this confusion distorts how people perceive individuals with NF1. Moreover, it is known that NF1 sufferers experience difficulty establishing social ties and developing good self-esteem [54], [55]: having their condition identified as the same disease as the “elephant man” had or given the name “elephant man disease” can only deepen this difficulty.

A press release published in 2001 by the board of directors of Quebec's neurofibromatosis association provides a good overview of the impact of this confusion on patients and their families: “The Board of Directors of the Association de la neurofibromatose du Québec (ANFQ) is concerned about the fact that a few members of the medical profession continue to associate neurofibromatosis with elephant man disease…. The stakes of this identification are considerable: considering the imaginary stigma created by the publicity given to the elephant man, it is a tragic event in a family to learn that one or more of its members, with neurofibromatosis, allegedly suffer from elephant man disease, that is, that their condition could degenerate to the point of being a monster. As a result, people with the disease and their close ones can become profoundly affected by the idea of such an eventuality.” [5] (Provided in English on the Association's web site; italics in the original.)

For those with NF1, believing they have Joseph Merrick's condition or knowing others believe this heavily compromises their hopes of a normal social life, employment that interests them, an enduring couple relationship, and raising children [56], [57]. When they learn that 50% of NF1 cases are inherited and that the condition is genetically dominant, they are likely, if they believe the condition they are at risk of transmitting is Joseph Merrick's condition, to dread that their children will look like the “elephant man”. A misunderstanding of this kind influences the process of arriving at decisions about having offspring: “When I was diagnosed, the physician told my husband and me that it would be best if I had my tubes tied, because all our children would have the disease. That's what I did, and I was stunned to learn later that what he had said wasn't true. First of all, the disease isn't that bad; and there were other solutions” (Béatrice, woman with NF1, Field Notes, 2007).

Furthermore, even though NF1's prevalence is similar to that of cystic fibrosis, one of the main problems faced by individuals with NF1 is to find a physician who can provide clinical management during their adulthood (all of the affected persons we have met mentioned this problem). NF1 sufferers often require referrals to specialists of several different kinds (geneticist, dermatologist, neurologist, psychologist and ophthalmologist), so their family physician must be well informed about their disease. And finally, the prospect of becoming like the “elephant man” needlessly complicates clinical management and does harm to the mental health of NF1 patients. We now know that the disease's visibility can have an impact on the quality of life of NF1 sufferers [58] and that there is a significant association between the disease's visibility and psychiatric morbidity [57], [59].

Conclusion

Given the nature of the problems we have just discussed, it could take no more than a few changes of attitude by the medical and scientific communities to make significant improvements. Physicians and scientists could send letters with corrective information to those media, publishers, and web sites that associate NF1 with the “elephant man” or refer to it as elephant man disease. It is noteworthy that we found no instances of the confusion between NF1 and Joseph Merrick's disease in the New York Times subsequent to the appearance of the letter from the National Neufibromatosis Foundation's past president [41].

NF1 specialists in various fields could take a more direct part in knowledge transfer and physicians' continuing education. Thus family physicians and pediatricians who have little familiarity with NF1 would learn that they can refer their patients with NF1 to NF clinics [2], [16], [60] and such specialists as geneticists, neurologists, and dermatologists. Patients and their family members would benefit from better tailored clinical management of their cases, perhaps even optimal management. This would include having access to better information [16], [19], appropriate genetic counseling [62], and psychological support from an early age [63], as well as receiving follow-up for learning disorders specific to NF [12], [64]. The literature shows that NF1 sufferers who are referred to specialists able to treat their physiological, psychosocial, and cognitive problems can look forward to significant improvements in their health, quality of life, and ability to integrate socially [12], [60].

On a different note, in the school setting, it is important for teachers to be informed that the main difficulties faced by children with NF1 are not related to intelligence but to learning problems and attention disorders [20], [65]: teachers could learn of the various teaching-and-learning approaches that exist to palliate these children's and teenagers' learning challenges and psychosocial fragility [57].

Finally, we hope this article will contribute in some small degree to showing the importance of the roles of the media and physicians in transferring knowledge about NF1 and thus in improving the conditions of life and health of people with NF1 and their families.