There were 467 individual responses to the survey, including 8 individuals with Fragile X (i.e., endorsing “I have Fragile X syndrome”), 20 professionals (i.e., endorsing “I am a professional who works with a person with FXS”), and 439 family members or caretakers (i.e., endorsing “I am a family member or caretaker of someone with FXS”). It should be noted that not everyone answered every question. Reporters described the individual with FXS on whom they were reporting as being mostly males (n = 397, 84.8%), with ages distributed across the lifespan (see Figure 1). See the data in Supplementary Table S1.
Figure 1. Survey respondent characteristics. FXS: Fragile X syndrome.
3.1. Results from Family Members/Caretakers
Major Concerns. Respondents completed the following question: “Rank these three areas (behavior, intelligence, physical abilities) from one to three to the extent it affects the person’s daily life–with one having the greatest impact and three having the least impact:” No other instructions or definitions were provided for this question on the survey. Each of the three areas of impact was described as having the greatest impact by at least some family members/caretakers, with behavior endorsed most commonly as having the greatest impact for males alone. However, for females alone, intelligence was endorsed as having the greatest impact. This question was answered by 429 family members/caretakers (see Figure 2). Physical abilities were the main concern in about 15% of FXS males aged 0–5 and 10% of FXS females age 22+ but were the main concern in less than 10% of all other groups. Behavior was by far the main concern in FXS males age 12 and under; however, in each older age category, intelligence was the main concern in a larger percent of males and, by age 22+, the main concern was divided almost equally between behavior and intelligence, suggesting that intellectual deficits are perceived as increasingly limiting as FXS males (and females) become older.
Figure 2. Primary concerns of family members/caretakers of males (A) and females (B) with FXS.
Problematic Symptoms. Family members/caretakers (438) completed the following question: “Check the five characteristics that have the greatest impact on the life of the person with FXS. Prioritize 1, 2, 3, 4, 5.” Out of potential symptoms listed (please see Appendix A for a full list), the following 5 symptoms had the highest weighted mean score (see Figure 3A): (1) Anxiety–anticipatory, e.g., of new/upcoming events and or social anxiety; (2) learning or intellectual disability (problems with abstract thinking, learning); (3) speech/language delays–expressive (speaking spoken language); (4) seizures; and (5) other. Anxiety was rated highest in males beginning at age 6 and in females across all ages, although in females, anxiety was rated highest at similar rates to learning problems. In young males (ages 0–5), expressive language delays were described as being the most problematic symptom. See the data in Supplementary Table S2.
Figure 3. Family member/caretaker’s 1st rank for characteristics that have the greatest impact on the life of the person with FXS (A), daily living skills most affected (B), family impact (C).
Daily Living Skills Most Affected. Family members/caretakers (436) answered the question “Check the top five areas of daily life the person with FXS is most affected by. Prioritize 1, 2, 3, 4, 5.” Out of 15 possible areas, the five abilities that received the highest weighted rank score were (see Figure 3B): (1) Ability to learn academic skills/reading/math; (2) ability to speak/communicate; (3) ability to control behavioral outbursts; (4) ability to take care of self; and (5) independence. Again, ability to speak was a higher-rated concern in the 0–5 group than the others; however, this was one of the most highly rated items throughout childhood and adolescence, while in adulthood, ability to live independently became the highest rated daily living skill concern. In general, ablity to speak, learn academics, control behavior, and perform self-care were fairly evenly rated as the skills weighted as most problematic across all age groups of males, while highest rated daily living problems for females reflected more social issues. See the data in Supplementary Table S3.
Family Impact. Family members/caretakers (431) answered the question “Which five specific aspects of daily living with FXS are the most challenging? Prioritize 1, 2, 3, 4, 5.” Out of twenty potential options, the following five aspects were ranked as the most challenging: (1) Handling behaviors (negative)—tantrums, aggression, spitting, cussing; (2) worry about the future; (3) always thinking—how are things going, what do I need to do next? Needing to always be ‘one step’ ahead; (4) person is unable to tell you what he/she wants/needs; and (5) supervision (see Figure 3C). See the data in Supplementary Table S4.
Treatment Priorities. Participants responded to the question “What are the top three aspects of Fragile X syndrome that you would like to see a drug treatment address, list in order of preference, with the most important one first.” After open coding of all three listed responses for all participants, the following themes emerged: Anxiety (e.g., “anxiety”, “social anxiety”, “reduce anxiety”), learning (e.g., “intellect”, “cognitive abilities”, “learning issues”), behaviors (e.g., “behavioral outbursts”, “tantrums”, “aggression”), Attention Deficit/Hyperactivity Disorder (ADHD) (e.g., “attention span”, “focus”, “impulse control”), communication (e.g., “speech delay”, “communication delay”, “language”), sensory (e.g., “sensory processing”, “hyperarousal”, “hand biting”), social (e.g., “social skills”, “social behaviors”, “connecting with others”), perseveration (“perseverative behaviors”, “saying the same thing”, “perseveration”), sleep (e.g., “sleep”, “sleeping”, “not sleeping”), mood (e.g., “depression”, “mood stability”, “mood swings”), motor (e.g., “fine motor skills”, “coordination”, “low muscle tone”), autism (e.g., “autism”, “autistic behavior”, “autistic tendencies”), eating (e.g., “weight”, “hunger”, “curb appetite”), and seizures (e.g., “seizures”, “seizure reduction”, “seizure control”). Notably, two family members/caretakers indicated that they were not interested in development of pharmaceutical treatments for symptoms of FXS. This question was answered by 439 family members/caretakers (see Figure 4A). See the data in Supplementary Table S5.
Figure 4. Family/caretaker (A) and professional drug (B) treatment priorities.
3.2. Voice of Professionals
Twenty professionals completed the survey. While this sample size prohibited investigations of mean response frequencies by age and sex for forced-choice questions, themes from free responses to the question about medication priorities are summarized below (see Figure 4B). Anxiety was most frequently described as the 1st priority for treatment, with almost half of professionals surveyed listing anxiety for their first priority.
3.3. Voice of Individuals with FXS
Only 8 individuals with FXS completed this survey, all of whom were female and ages 13 years or older. Given this small number, we focus here on individual answers to the free response question rather than group means for the forced-choice questions. In parallel with responses from families, anxiety was most commonly listed as a priority for treatment for this group of individuals with FXS (see Figure 5A). Due to the limited number of respondents, a weighted mean score was calculated as described above for all of the responses received (see Figure 5B).
Figure 5. Drug treatment priorities as reported by 8 females with FXS. A: Drug treatment priorities ranked first as reported by 8 females with FXS. B: Drug treatment priorities, as a mean weighted rank score of all responses, as reported by 8 females with FXS.