Neurofibromatosis type 1 (NF1) is a genetic disorder characterized by a predisposition to develop multiple benign tumors. A major feature of NF1 is the development of localized cutaneous neurofibromas. Cutaneous neurofibromas manifest in > 99% of adults with NF1 and are responsible for major negative effects on quality of life. Previous reports have correlated increased burden of cutaneous neurofibromas with age and pregnancy, but longitudinal data are not available to establish a quantitative natural history of these lesions. The purpose of this study is to conduct a prospective natural history study of 22 adults with NF1 over an 8-year period to quantify cutaneous neurofibroma number and size. The average monthly increase in volume for cutaneous neurofibromas was 0.37 mm3 in the back region (95% CI (0.23, 0.51), p < 0.0001), 0.28 mm3 in the abdominal region (95% CI (0.16, 0.41), p < 0.0001), and 0.21 mm3 in the arm/leg region (95% CI (0.08, 0.34), p = 0.0022). The number of cutaneous neurofibromas significantly increased in the back (slope = 0.032, p = 0.011) and abdominal (slope = 0.018, p = 0.026) regions, while the leg/arm regions retained a positive trend (slope = 0.004, p = 0.055). The number and volume of cutaneous neurofibromas significantly increased over an 8-year timespan; however, the rate of increase is variable by individual and body region. These findings may provide insight into cutaneous neurofibroma development and benefit researchers considering clinical trials targeting cutaneous neurofibromas.

Background: It is critical to understand the wide-ranging clinical and non-clinical effects of genome sequencing (GS) for parents in the NICU context. We assessed parents’ experiences with GS as a first-line diagnostic tool for infants with suspected genetic conditions in the NICU. Methods: Parents of newborns (N = 62) suspected of having a genetic condition were recruited across five hospitals in the southeast United States as part of the SouthSeq study. Semi-structured interviews (N = 78) were conducted after parents received their child’s sequencing result (positive, negative, or variants of unknown significance). Thematic analysis was performed on all interviews. Results: Key themes included that (1) GS in infancy is important for reproductive decision making, preparing for the child’s future care, ending the diagnostic odyssey, and sharing results with care providers; (2) the timing of disclosure was acceptable for most parents, although many reported the NICU environment was overwhelming; and (3) parents deny that receiving GS results during infancy exacerbated parent–infant bonding, and reported variable impact on their feelings of guilt. Conclusion: Parents reported that GS during the neonatal period was useful because it provided a “backbone” for their child’s care. Parents did not consistently endorse negative impacts like interference with parent–infant bonding.

Objective To assess the perspectives of adults with neurofibromatosis 1 (NF1) regarding cutaneous neurofibroma (cNF) morbidity, treatment options, and acceptable risk–benefit ratio to facilitate the design of patient-centered clinical trials. Methods An online survey developed by multidisciplinary experts and patient representatives of the Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) cNF Working Group was distributed to adults with NF1 (n = 3,734) in the largest international database of individuals with any form of NF. Eligibility criteria included self-reported NF1 diagnosis, age ≥18 years, ≥1 cNF, and ability to read English. Results A total of 548 adults with NF1 responded to the survey. Respondents ranked appearance, number, and then location as the most bothersome features of raised cNF. Seventy-five percent of respondents considered a partial decrease of 33%–66% in the number or size of cNF as a meaningful response to experimental treatments. Most respondents (48%–58%) were willing to try available cNF treatments but were not aware of options outside of surgical removal. Regarding experimental agents, respondents favored topical, then oral medications. Most individuals (>65%) reported being “very much” or “extremely willing” to try experimental treatments, especially those with the highest cNF burden. Many respondents were not willing to tolerate side effects like nausea/vomiting (51%) and rash (46%). The greatest barriers to participation in cNF clinical trials were cost of participation and need to take time off work. Conclusions Most adults with NF1 are willing to consider experimental therapies for treatment of cNF. These data will guide the design of patient-centered clinical trials for adults with cNF.

Background/Aims: More than 99% of individuals with neurofibromatosis 1 develop cutaneous neurofibromas, benign nerve sheath tumors that manifest as nodules on the skin. These cutaneous neurofibromas emerge with age, appearing most commonly in adolescence. Nevertheless, few data have been published on how adolescents with neurofibromatosis 1 feel about cutaneous neurofibromas. The purpose of this study was to assess the perspectives of adolescents with neurofibromatosis 1 and their caregivers regarding cutaneous neurofibroma morbidity, treatment options, and acceptable risks-benefits of treatment. Methods: An online survey was distributed through the world’s largest NF registry. Eligibility criteria included self-reported neurofibromatosis 1 diagnosis, adolescent child ages 12–17 years, ≥1 cutaneous neurofibroma, and ability to read English. The survey was designed to collect details about the adolescent’s cutaneous neurofibromas, views on morbidity related to cutaneous neurofibromas, social and emotional impact of cutaneous neurofibromas, communication regarding cutaneous neurofibromas, and views regarding current and potential future cutaneous neurofibroma treatment. Results: Survey respondents included 28 adolescents and 32 caregivers. Adolescents reported having several negative feelings about cutaneous neurofibromas, particularly feeling worried about the potential progression of their cutaneous neurofibromas (50%). Pruritus (34%), location (34%), appearance (31%), and number (31%) were the most bothersome cutaneous neurofibroma features. Topical medication (77%–96%), followed by oral medication (54%–93%), was the most preferred treatment modality. Adolescents and caregivers most often replied that cutaneous neurofibroma treatment should be initiated when cutaneous neurofibromas become bothersome. The majority of respondents were willing to treat cutaneous neurofibromas for at least 1 year (64%–75%). Adolescent and caregivers were least willing to risk pain (72%–78%) and nausea/vomiting (59%–81%) as a cutaneous neurofibroma treatment side effect. Conclusions: These data indicate that adolescents with neurofibromatosis 1 are negatively impacted by their cutaneous neurofibromas, and that both adolescents and their caregivers would be willing to try longer-term experimental treatments.

As the uptake of population screening expands, assessment of medical and psychosocial outcomes is needed. Through the Alabama Genomic Health Initiative (AGHI), a state‐funded genomic research program, individuals received screening for pathogenic or likely pathogenic variants in 59 actionable genes via genotyping. Of the 3874 eligible participants that received screening results, 858 (22%) responded to an outcomes survey. The most commonly reported motivation for seeking testing through AGHI was contribution to genetic research (64%). Participants with positive results reported a higher median number of planned actions (median = 5) due to AGHI results as compared to negative results (median = 3). Interviews were conducted with survey participants with positive screening results. As determined by certified genetic counselors, 50% of interviewees took appropriate medical action based on their result. There were no negative or harmful actions taken. These findings indicate population genomic screening of an unselected adult population is feasible, is not harmful, and may have positive outcomes on participants now and in the future; however, further research is needed in order to assess clinical utility.