Misunderstood terms and concepts identified through user testing of educational materials for fragile X premutation: “Not weak or fragile?”

Complicated genetic mechanisms and unpredictable health risks associated with the FMR1 premutation can result in challenges for patient education when the diagnosis is made in a newborn. From October 15, 2018, to December 10, 2021, North Carolina parents could obtain FMR1 premutation results about their newborns through a voluntary expanded newborn screening research study. The study provided confirmatory testing, parental testing, and genetic counseling. We developed web‐based educational materials to augment information about fragile X premutation conveyed by a genetic counselor. Many genetics education materials are developed for the lay population. However, relatively little research is published on how well individuals understand these materials. We conducted three rounds of iterative user testing interviews to help refine web‐based educational materials that support understanding and self‐paced learning. The participants included 25 parents with a 2‐year college degree or less and without a child identified with fragile X syndrome, premutation, or gray‐zone allele. Content analysis of interview transcripts resulted in iterative changes and ultimately saturation of findings. Across all rounds of interviews, there were two terms that were commonly misunderstood (fragile and carrier) and two terms that elicited initial misconceptions that were overcome by participants. Many also had difficulty understanding the relationship between fragile X premutation and fragile X syndrome as well as appreciating the implications of having a “fragile X gene.” Website layout, formatting, and graphics also influenced comprehension. Despite iterative changes to the content, certain issues with understandability persisted. The findings support the need for user testing to identify misconceptions that may interfere with understanding and using genetic information. Here, we describe a process used to develop and refine evidence‐based, understandable parental resources on fragile X premutation. Additionally, we provide recommendations to address ongoing educational challenges and discuss the potential impact of bias on the part of expert content developers.


| INTRODUC TI ON
Expansion of cytosine-guanine-guanine (CGG) repeats within the 5′ UTR of the fragile X messenger ribonucleoprotein 1 (FMR1) gene (MIM# 309550) can lead to an array of fragile X-associated conditions with highly variable phenotypic manifestations.Fragile X syndrome (FXS) is the most common inherited form of intellectual disability.FXS occurs when expansion to over 200 CGG repeats (also known as a full mutation) leads to hypermethylation of the FMR1 gene and subsequent loss of the associated gene product, FMRP.Although estimates vary, ~1 in 200 females and 1 in 430 males carry the FMR1 premutation, which may result in an increased risk of having a child or grandchild with FXS (Owens et al., 2018;Tassone et al., 2012).Defined as 55-200 CGG repeats without hypermethylation, FMR1 premutations also are associated with an increased risk for an array of health conditions, including fragile X-associated tremor/ataxia syndrome, fragile X-associated primary ovarian insufficiency, fragile X-associated neuropsychiatric disorders or conditions, various autoimmune disorders, and numerous additional conditions (Bailey Jr. et al., 2008;Hagerman et al., 2018;Johnson et al., 2020;Wheeler et al., 2017).Because of limited natural history data, the neurodevelopmental impact on children remains less clear but includes risk for sensory, learning, and attention issues (Raspa et al., 2018;Wheeler et al., 2017).Uncertain, unpredictable, and highly variable expressivity among the various fragile X-associated conditions is mediated by less well-understood genetic mechanisms, presenting patient education challenges for genetic counseling (Finucane et al., 2012).
From October 15, 2018, to December 10, 2021, North Carolina parents could obtain FMR1 premutation results for their newborns through a voluntary expanded newborn screening (NBS) research study called Early Check (Bailey Jr. et al., 2019).Early Check participation was offered to all babies who had NBS in North Carolina.
The Early Check panel included the FMR1 full mutation, with the option to also receive premutation results (Okoniewski et al., 2019).
Disclosing these results and helping parents understand their wideranging implications led to multiple genetic counseling sessions for parents.Multilayered patient education materials were developed to further support parents and families.
A certified genetic counselor on the Early Check team relayed confirmatory results via a HIPAA-compliant video conferencing platform.The telegenetic counseling content was complex and included a review of the results and an explanation of the uncertain impact on the baby's future development, temperament, and learning.The potential implications for siblings, future children, parents, and other relatives were also discussed.Additionally, the opportunity to receive research-based neurodevelopmental research evaluations for the infant was provided.Parental testing was offered, and those results were disclosed and explained during a subsequent telegenetic counseling session.
Because Early Check is a population-based study, we anticipated parents of participating infants would have little or no prior understanding of FXS or fragile X premutation (FXPM) and limited genetics literacy.Yet even when simplified, the genetic counseling included concepts with high cognitive demand.Evidence suggests comprehension challenges may be further compounded by shock and anxiety, which may be experienced by parents receiving unexpected results about their asymptomatic newborns and/or themselves (Salm et al., 2012).Together, these variables can increase the occurrence of misunderstanding or misremembering the genetic counseling information (Buchbinder & Timmermans, 2012).Furthermore, ambiguous and uncertain implications of test results, preconceived notions of personal risk, social context, and low health, and genetic literacy have also been found to affect comprehension and recall of genetic counseling information (Haga et al., 2014;Kelly et al., 2014;Klitzman, 2010;Vos et al., 2011Vos et al., , 2012)).

What this paper adds to the topic
Many patient and parent educational materials have been developed to explain genetic conditions to the lay population, yet relatively little research has been published regarding challenges identified during user testing.
Incorporating parent input, via user testing interviews, into the educational materials refinement process revealed unexpected misunderstanding of terminology and concepts.
User testing can reveal bias imparted by expert content developers.
information for parents to access as needed.These online materials also serve as a primer of fragile X-related concepts, with links to existing reliable websites and resources.We purposely focused content on the implications for newborns confirmed with the premutation and the health and reproductive implications for parents who subsequently learn that they have the premutation.A section on the genetic mechanisms of fragile X-related conditions was also included for those seeking to understand how the conditions occur (RTI International, n.d.-a, n.d.-b).
Even with knowledge of plain language best practices and expertise in communicating about genetic conditions, it was prudent to assume that our development team members were subject to bias that could lead them to overlook written or visual components that may be unclear to the intended population.Thus, we conducted user testing with parents in the general population who were naïve to fragile X-associated conditions to help inform the refinement of web-based materials that supported understanding and self-paced learning.This study highlights the terminology and key concepts commonly misunderstood by user testing participants and presents recommendations to address ongoing educational challenges and potential biases among expert content developers.

| Website content and format development
The educational materials were intended for parents and relatives of infants identified with an FMR1 premutation through populationbased Early Check screening, anticipated as moderate to low genetic literacy and no knowledge of FXPM.The content was focused on FXPM but included information on FXS due to the increased risk of having a future child with FXS.In addition, information about FXS was included in the content, as parents had their child screened for FXS and it was important to provide clarity that their child did not have this diagnosis.The website development team included master's-and doctoral-level researchers, certified genetic counselors, child psychologists with expertise in FXS, and specialists in health communication, data visualization, and web development.We applied plain language and health literacy principles and website design and navigation best practices and restricted the materials to a 7th-grade reading level or lower.Our objective was to develop web content that could be understood by someone in the general public with little to no knowledge about FXS or FMR1 premutation.In keeping with plain language principles and mirroring language used by advocacy organizations, we included the terms fragile X mutation and premutation rather than FMR1 expansion.We also avoided a full explanation of the outdated gene name fragile X mental retardation 1, which was still in use at the time.In 2022, the official FMR1 gene name was updated from fragile X mental retardation 1 to fragile X messenger ribonucleoprotein 1 (EFXN) (FRAXA Research Foundation, 2022).When our educational materials were developed in 2018, we referenced the term fragile X gene to mirror its prevalence in existing family-facing websites.This term now appears to be replaced more frequently by the gene name, FMR1, although the term fragile X gene persists in web searches.Currently, the evocative terms premutation and mutation continue to be used to discuss FMR1 expansion and inheritance of associated conditions (Spector et al., 2021).
The development team used formatting principles to present primary or "key" content deemed critical.We also incorporated self-navigation to give users access to more detailed content and to supplementary content, if desired.A section on genes and the mechanisms of inheritance was framed as helpful to understanding how fragile X-associated conditions run in families.The development team chose to present this section separately from key content on implications for infants and children, reproductive risk, and the value of parental testing.The presentation of this information was intentional due to the high cognitive demand of genetics concepts.Also, we anticipated that many people, particularly those with lower literacy, may not seek this level of detail.Thus, we provided content structured in a way that addresses a range of parental educational preferences and needs.Appendix 1 presents excerpts from the original content and the final content.

| Participants
Participants were recruited via a local market research firm that used a standardized instrument developed by the research team to screen for eligibility for each round.
Parents were eligible to participate if they were aged 18 or older and had a child between 3 and 12 months of age.Individuals with higher than a 2-year college degree and/or individuals employed in the health care field were excluded from participation.Our objective was to recruit participants that represented the general North Carolina population of new parents unlikely to be familiar with fragile X-associated conditions.A total of 25 parents whose children had a mean age of 8 months (range of 3 to 12 months) participated in the interviews.We recruited an equal number of white and Black participants (44%, n = 11, respectively), and 16% of respondents (4/25) identified as Hispanic.All participants were fluent in English and comfortable with the user testing interviews conducted in English.A majority of participants (64%, n = 16/25) had some college or technical school experience but no college degree.Only one participant had heard of FXS or FXPM prior to the interview.Participant characteristics are shown in Table 1.

| User testing
Three iterative rounds of one-on-one interviews (9 participants in Round 1, 8 participants in each of Round 2 and Round 3) were conducted to receive input on the website content and user experience.
We assessed the following components: • Understandability of the written and graphic information, including areas that led to confusion, gaps, and misconceptions The research team made responsive edits to the language, visuals, and website formatting iteratively between rounds of data collection in response to participant feedback and noted problematic aspects.In response to input from the previous round of interviews, and to ensure refinements did not introduce confusion, a semi-structured interview approach was used to probe participants for feedback on website changes.Saturation was met when no new content or layout issues were identified by participants.Following enhancements to the pages, the research team assessed the reading grade level to ensure that the content retained a reading level no higher than the 7th grade.
In Round 1 of the interviews, participants reviewed printed copies of the website content.This was intended to assess user comprehension and clarity of the content.In Round 2, participants viewed the content on the pilot website.Formatting, layout, and responses to graphical components, including diagrams and GIFs, were assessed.In Round 3, while we continued to assess how information was understood, we also focused on the concepts that were most challenging to understand in the previous rounds of interviews.
Additionally, animated videos with voiceover were added and assessed in Round 3.

| Data analysis
The analysis was conducted by a genetic counselor and an experienced qualitative researcher.A codebook was developed based on review of the verbatim transcripts, and content analysis was performed to identify and record themes.Themes were tabulated and compared within and across the three rounds of interviews to identify areas of misunderstanding or issues related to formatting or visual presentation that persisted despite iterative improvements to the website content.Because of the goal of the research, we used counts and percentages in addition to reporting themes.

| RE SULTS
Across all rounds of interviews, there were two terms that were commonly misunderstood and two terms that came with initial misconceptions that were possible to overcome without content modification.Many also had difficulty understanding the relationship between fragile X premutation and fragile X syndrome and why information about fragile X syndrome was included in materials intended for parents of children with FXPM.Additionally, some participants did not comprehend the implications of having a fragile X gene.

| Misunderstood terms
Four terms commonly used to describe fragile X-associated disorders-fragile, carrier, mutation, and premutation-were found to hold alternate meanings for many participants.For the terms fragile and carrier, in some cases these alternate meanings led to persistent misunderstanding that was not immediately evident to the interviewers.For the terms mutation and premutation, the alternate meanings did not seem to contribute to lasting misunderstandings.

| Fragile
When directly asked, nearly half of all participants (40%, n = 10/25) reported an expectation that babies with FXS would exhibit some type of physical or emotional fragility.

| Initial misconception associated with terms mutation and premutation
Upon first introduction, the terms mutation and premutation evoked science fiction references from 3 of 25 participants (12%), which may have been distracting to the participants but did not appear to be associated with downstream misunderstanding of key concepts.
Premutation, though, that's like a pretty scary word.
Mutation, you know, I be thinking about the Ninja Turtles. [laughter] -Male, high school education Now when it says that "if your baby has the fragile X premutation, you could also say he or she is a premutation carrier," you're saying that my child is an X-Man or something?
-Male, some college/technical education

| Challenges understanding the relationship between fragile X premutation and fragile X syndrome
Overall, 20 of the 24 participants (83%) who reviewed sections introducing and differentiating the terms fragile X syndrome and fragile X premutation did not understand the distinction and/or the relationship between the two terms.Participants' lack of familiarity with the terms, together with the similar appearance of the words and abbreviations, seemed to result in the lack of differentiation.Furthermore, participants did not understand why fragile X syndrome was being included in the information if the intended recipients are parents or relatives of a child diagnosed with fragile X premutation.They perceived the conditions were the same, or that one led to the other.-Female, some college education The genetics section had been intentionally framed by the content developers as helpful but supplementary information but provided helpful context.A prominent statement to clarify the hereditability of fragile X-associated disorders was therefore added as top-level content (see Appendix 1).

| Implications of having a fragile X gene
Among the participants in the Round 1 and Round 2 interviews, 47% (n = 7/15) conflated the presence of the gene with the disease state and subsequently assumed higher risk for females with two "fragile X genes." Okay, so reading this section, this is where it gets a little bit confusing because it says, it says everyone has at least one fragile X gene.So does that mean like the gene is dormant, or… It leaves you with questions, so I'm like are you saying everybody has it [fragile X premutation]?
-Female, some college We noted interviewees' expectation that females (with two "fragile X genes") would more often or more severely be affected by FXS than males with only one copy of the gene.To reduce conflation of the gene name with the disorder and to avoid the strong associations with the term fragile, the phrase fragile X gene was replaced with the more neutral name FMR1 following Round 2. Additionally, we added language to describe FMR1 as an important gene for brain development.However, difficulty with the concept persisted for two of six Round 3 interview participants (33%), and the accompanying animation (see Figure 1) did not clarify the concept for all participants.
In response, one participant was unable to comprehend the benefit of having a second working fragile X gene: So girls are way higher risk [for fragile X syndrome], right?
-Female, 2-year college degree Following Round 3 interviews, additional and prominent content was added to highlight the normalcy of having at least one working FMR1 gene and its importance for healthy brain development.

| Website layout
Our user interviews revealed how the application of formatting and visuals supported or hindered comprehension.

F I G U R E 1
Web page screen shots from text and video to clarify role of the FMR1 gene in development.[Video Narrator] An important gene on the X chromosome tells our bodies to make a chemical needed in the brain.[…] Everyone has at least one FMR1 gene.Girls have two X's, so they have two FMR1 genes.Boys have one X and one Y, so they have one FMR1 gene….[In a later section, explaining the impact of the full mutation in males vs. females:] Why is fragile X syndrome usually milder in females?This is because unlike males, females have two FMR1 genes.Even when one gene isn't working, the other gene still makes some of that important FMRP brain chemical.So females with fragile X syndrome may have fewer or milder symptoms.
[Video Narrator] An important gene on the X chromosome tells our bodies to make a chemical needed in the brain.
[…] Everyone has at least one FMR1 gene.Girls have two X's, so they have two FMR1 genes.
Boys have one X and one Y, so they have one FMR1 gene….
[In a later section, explaining the impact of the full mutation in males vs females:] Why is fragile X syndrome usually milder in females?This is because unlike males, females have two FMR1 genes.Even when one gene isn't working, the other gene still makes some of that important FMRP brain chemical.So females with fragile X syndrome may have fewer or milder symptoms.

| Formatting for visual clarity
In response to confusion in Round 1 interviews about the FXPM as compared to FXS, we used a color-coding scheme to distinguish information related to FXPM and FXS.We also presented information about FXPM and FXS in a callout box format to aid in the differentiation between the two conditions.

| Enabling desired level of detail with emphasis on key content
Participants commented explicitly or implicitly on the volume of text and detail on each page or section, which led some participants to overlook key information.We observed and assessed interviewees' mentions of personal learning style to understand whether the presentation of the website content was meeting learning needs or preferences in terms of the volume of text, use of bulleted information, and images and other visuals.More than half of participants (71%, n = 12/17), spontaneously voiced their personal learning style and approaches for engaging with information during the interview, exemplifying a broad range of preferences.Participants' comments included preferences for auditory and visual content as opposed to written information.Some described preferences for brief and bulleted information, whereas others preferred more detailed content.Some expressed that they typically skim content to glean the main points, with one participant describing themself as a "picker and chooser" of information, whereas other participants described themselves as "readers" or people who "[pick] up on the details" of what is presented.
To respond to participants' expressed preference in learning styles and to remain consistent with best practices for web content development, we made iterative revisions to list critical takeaway information near the top of each page while still offering supplementary detail below for those who desire it.Consequently, all supplementary detail was presented as a layer of expandable text or linked content.

| Use of visuals to enhance understanding
Some participants were drawn to images, whereas others focused primarily on the written text on the page and dismissed the images entirely.One image and its prominent placement was found to cause misunderstanding of the associated content.The image was of a tired-or stressed-looking mother that was placed at the top of a section intended to support the emotional health and well-being of new parents, normalize feelings of stress, and help parents distinguish between mild cases of the "baby blues" and post-partum depression.
Participants, including male participants, found the image relatable, with more than half of participants (57%, n = 8/17) commenting that the subject looked like any new mother.
However, the location of the image in a section dedicated to "Feeling Overwhelmed" contributed to misunderstanding of the intent of the information.Specifically, 11 of the 16 participants (69%) reviewing the content in the Round 1 and Round 2 interviews assumed parents of babies with the premutation would be stressed or anxious because of the diagnosis in their child.We explored this concern in the interviews and determined this persistent issue was a result of the vague section title and placement relative to information on FXPM.After Round 2 interviews, this content and the associated image were moved to a less prominent location within a section on getting support, which also included a more uplifting image of women supporting each other.The title "Feeling Overwhelmed" was changed to "If You're Feeling Overwhelmed."Following these changes, each of the four subsequent participants understood this content to be general information aimed at all new parents and did not presume this was a causative relationship between FXPM in children and parental stress.

| DISCUSS ION
Extensive genetics education materials exist for the lay population, yet relatively little research is published that describes results of user testing to improve understandability and acceptability.One-on-one user testing allowed us to observe firsthand which content and visual components caused difficulty and misunderstanding for interview participants.Interviewee responses provided insight into the root causes of misunderstandings and strategies for improvement.Furthermore, conducting interviews in multiple rounds enabled us to refine the content and retest with novel participants.

| Implications of terminology and genetics concepts
Increasing awareness of the various potential barriers to effective health communication has resulted in valuable efforts to promote the use of plain language in multiple healthcare settings, including genetics (Shoemaker et al., 2014;van der Giessen et al., 2021).
Although we employed plain language guidelines, our interviewees' valid but different understandings of fragile and carrier illustrate the potential for ambiguity that can cause misunderstanding of common, apparently simple terms.Alternate interpretations, sometimes referred to as preconceived notions or vernacular misconceptions, may be influenced by factors such as education, emotional issues, and social context (Klitzman, 2010).Not surprisingly, subtle differences in interpretation were more difficult for us to detect.Our initial failure to recognize participants' familiarity with carrier in the context of communicable rather than heritable disease was only uncovered after we thoroughly probed for nuanced alternate interpretation of terms.Similar misconceptions have been shown to persist even after genetic counseling (Klitzman, 2010), underscoring the importance of employing methods to elicit demonstrated understanding or familiarity.
The genetics community has also recognized the need to review and improve the precision of some genetics terminology.For example, for more accurate and precise communication, there has been movement toward standardizing the use of pathogenic variant in place of mutation and encouraging the clarification of ambiguous or outdated genetics terminology (Jarvik & Evans, 2017;Richards et al., 2015).Additionally, the recent shift to naming genes based on function rather than associated disorder (Bruford et al., 2020) is more accurate.Notably, however, regardless of our use of the less evocative FMR1 gene name, some of our interviewees appeared to conflate the mere presence of a gene with a disease state.Once identified, replacing deeply held misunderstandings, misconceptions, or alternate interpretations of common terms appears to require repeated and prominent clarifying language with strong visual emphasis.In some cases, additional content must be added for clarity which may deviate from the intention to include simple language and terminology.User testing is unlikely to be able to identify and offset all misunderstandings, but particularly problematic or pervasive issues can be addressed.

| Implications of layout, formatting, and visuals
We were able to resolve several areas of misunderstanding by providing alternative content presentation.This included additional visual cues such as a color-coding scheme, callout boxes, and the addition of side-by-side comparison tables for clarity or emphasis.
Additional visual cues also reduced overlooking key content.et al. (2020) were able to improve understanding in 100% of participants by providing visuals to illustrate common genetic terms.However, visual aids, GIFs, and photographs can lead to confusion or distraction (Wynn et al., 2018), making them an important target for user testing to evaluate acceptability and utility.Video with voiceover should be considered to improve comprehension.

| Implications of health communication best practices
The distinction between FXPM and FXS remained unclear to participants despite reframing, verbal clarifications, and the addition of visual cues mentioned above.Notably, incorporating website design best practices like minimal word count and expandible text to promote self-navigation may have contributed to this lack of clarity.We purposely focused attention on the implications of FXPM (emphasized as key content) rather than on its complex genetic etiology.
Conversely, we framed the genetics section as supplementary detail.
During data analysis following the Round 3 interviews, it was recognized that several participants had reported improved understanding of FXPM and its relationship to FXS only after they reviewed the detailed genetics section.This suggests that a rudimentary understanding of the underlying genetic etiology provided context necessary for distinguishing between FXS and FXPM.Similarly, our experience indicates that presenting more information about genetic mechanisms as key content might help to contextualize the term carrier.
Genetics content does not easily align with health communication best practices.When feasible, additional user testing or evaluation of materials once they are in use should be undertaken to evaluate and refine the highest-level concepts that are required for downstream understanding.These should then be highlighted as key content and prioritized over generally preferable practices such as minimal word count, low cognitive demand, and self-navigation.

| Implications of bias
The importance of user testing to develop and refine health education materials has been well documented (Wynn et al., 2018).In addition to cultural, racial, and linguistic biases, a cognitive bias known as "the curse of knowledge" may be relevant to genetics education and genetic counseling (Lourenco & Baird, 2020).With this bias, experts' own ease and familiarity with a subject matter causes them "to struggle to re-create the state of mind of a novice" and potentially blinds them to challenging content (Xiong et al., 2020).Only through interviews with an audience unfamiliar with fragile X-associated conditions were we able to identify alternate interpretations of terms that the team did not anticipate or initially recognize.

| Limitations
Participant review of the content transpired with an interviewer and observer present to monitor progression throughout pages and to ask questions throughout, which did not mirror how parents/family members will be exposed to the content in real life.Additionally, a majority of user testing participants were completely naïve to FXS and FXPM, only learning about the conditions during the interviews.
In the Early Check study, many parents who visit the website will only do so after they have had an initial counseling session with the Early Check genetic counselor.Consequently, in many cases, parents reviewing the website content will likely have some basic understanding of FXPM and some familiarity with key concepts and terms.
However, the links are intended to be shared with others, including extended family members, so some individuals viewing the website may have very little background or introduction.The interview participants did not have a baby with a fragile X-associated condition or other known genetic condition; consequently, the content did not evoke emotion that may be present in a true review of the website, which may affect reaction or comprehension.

| CON CLUS ION
Overall, our findings underscore the importance of incorporating user testing into the development of genetics educational materials to maximize the accessibility and value of genetics information across the intended population.To complement user testing by the members of the naïve target population, stakeholder engagement should be considered early in the materials development process to inform content and increase relevance to the target audience (Haynes et al., 2022;Miller et al., 2015).
We recommend that developers of educational materials use a structured approach for material development and follow best practices and adult learning theory to the extent possible, with the expectation that complex genetic topics may require compromise and balance; that is, the ideals of simplicity and self-direction versus the additional detail and sequential ordering that may best improve understanding.Existing tools and guidance, such as the Patient Education Materials Assessment Tool (PEMAT) and the PEARL rubric, are recommended to evaluate materials (Haynes et al., 2022;Shoemaker et al., 2014), Finally, user testing should be conducted in iterative rounds to allow for refinement.
To inform future research, particularly research conducted in large and unselected populations, it would be valuable to identify the minimum knowledge of underlying genetic mechanisms required for comprehension of potential health and reproductive risk.It would also be useful to explore a wider array of terms and concepts commonly used to explain genetics and genomics that impart different meanings to people of various ethnic, racial, and educational backgrounds and the ability of interactive web-based educational tools to ensure accurate decoding.
of these obstacles, we developed plain language web-based educational content following best practices for webbased educational content development.To the extent possible, we avoided technical medical or genetics jargon.The materials reiterate and augment information provided during Early Check premutation genetic counseling.Our goal was to provide an ongoing source of K E Y W O R D S bias, communication, FMR1 premutation, fragile X premutation, genetic counseling, newborn screening, parental resources What is known about this topic Identification of an FMR1 premutation presents significant genetic counseling and patient education challenges, such as anxiety about the diagnosis, uncertainty associated with phenotype, preconceived notions of risk, challenges associated with low health literacy, and misunderstanding or misremembering of information provided in a genetic counseling session.

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Acceptability and emotional reaction to the information (e.g., whether it evoked fear or worry or reassurance) • Utility of content layout to enhance visual clarity, such as the use of boldface and a color-coding scheme • Website layout and self-navigation tools Interviews were conducted in person in two cities in North Carolina.Each interview lasted about an hour, was led by an experienced qualitative interviewer, and was observed by a certified genetic counselor on the Early Check research team.Participants reviewed a draft website during the interview session.Because of time constraints, not all participants reviewed all of the educational content, which is reflected in the reporting of the results.Interviews were audio-recorded and transcribed for analysis.
Okay.I'm, I'm confused right away because the first thing says your baby does not have fragile X syndrome.Why does it say that if I'm supposed to be reading about it?-Female, some college education I was just looking at the difference between the fragile and then the effects-wait, I forgot, hold on, I was thinking, but, oh, yeah, that they carry it… Is it like the same thing or the same condition, or is it like two different… -Female, some college education Formatting refinements to distinguish the full mutation more clearly from the premutation included the addition of a color-coding scheme and callout boxes plus additional framing language.Despite the addition of these cues, a majority of interviewees in the Round 2 and Round 3 interviews remained uncertain about the distinction and relationship between FXS and FXPM.I don't think they would just jump in and say, yeah they have this syndrome…okay this [premutation] is the possibility, then we do more testing, could be a possibility of the syndrome, but that comes further along with doing more tests.-Female, some college education The analysis revealed spontaneous comments from 6 of 25 participants (24%) indicating improved understanding of the relationship between FXS and FXPM after reviewing the detailed content on genetics and inheritance.I think that maybe should have been explained before the thinking [about] testing.If we're about to talk about what causes it, it's kind of weird to think about getting tested and then we don't even know what causes it.
Participant characteristics weak bones, like a fragile, just timid baby; somebody that you have to be very careful with[…].Have you ever seen the movie Glass?-Female, high school education TA B L E 1 (n = 5/16) also voiced an initial expectation that weakness or fragility would be a feature of FXPM, all but two participants readily accepted the reassurance that features were expected to be absent or mild.There's a name, weak or fragile, but they [affected children] don't seem like that.So it gives them that reassurance like, they're not going to look weak or fragile, because if you say "fragile X," they're going to think, oh my gosh, if they fall, they might break something.It just seems when you say "fragile."-Female,somecollege education/technical education However, one Round 3 interview participant misread the reassuring statement, overlooking the word not.Well, I've heard it before, like I think AIDS I think, or herpes, like diseases.There, there are carriers and those that aren't carriers, like they can get, let me see, they could get sick, but they can't pass it to somebody else, but the carrier, they can pass it to someone else.-Male, some college Following the Round 3 interviews, based on the continued association of the term carrier to the context of communicable disease, a clear and prominent sentence was added to the top of the first page to reiterate the genetic rather than communicable etiology of these conditions (see Appendix 1): "It's genetic.People can't catch it like a cold or virus."