The 8th International RASopathies Symposium: Expanding research and care practice through global collaboration and advocacy.

Germline pathogenic variants in the RAS/mitogen-activated protein kinase (MAPK) signaling pathway are the molecular cause of RASopathies, a group of clinically overlapping genetic syndromes. RASopathies constitute a wide clinical spectrum characterized by distinct facial features, short stature, predisposition to cancer, and variable anomalies in nearly all the major body systems. With increasing global recognition of these conditions, the 8th International RASopathies Symposium spotlighted global perspectives on clinical care and research, including strategies for building international collaborations and developing diverse patient cohorts in anticipation of interventional trials. This biannual meeting, organized by RASopathies Network, was held in a hybrid virtual/in-person format. The agenda featured emerging discoveries and case findings as well as progress in preclinical and therapeutic pipelines. Stakeholders including basic scientists, clinician-scientists, practitioners, industry representatives, patients, and family advocates gathered to discuss cutting edge science, recognize current gaps in knowledge, and hear from people with RASopathies about the experience of daily living. Presentations by RASopathy self-advocates and early-stage investigators were featured throughout the program to encourage a sustainable, diverse, long-term research and advocacy partnership focused on improving health and bringing treatments to people with RASopathies.

Feasibility and acceptability of a telehealth intervention for improving peer relationships for adolescents with neurofibromatosis type 1: a single-arm pilot study.

OBJECTIVE: Elevated rates of social difficulties are evident for children and adolescents with neurofibromatosis type 1 (NF1) but the effects of social skills interventions have not been investigated for this population. The Program for the Education and Enrichment of Relational Skills (PEERS®), a widely established social skills intervention in autism spectrum disorders with expansion to other conditions, was recently modified to be offered virtually. This study examined the feasibility and acceptability of this telehealth intervention. METHODS: 27 adolescents with NF1 with social skills difficulties and at least 1 caregiver enrolled in the study. 19 of those participants (Mage = 14.21 years, SD = 1.63; 7 females; 79% White) completed PEERS® via telehealth in a single-arm pilot study. Dropout rates, attendance records, helpfulness of the curriculum topics and caregiver-reported acceptability, including ratings on the Treatment Acceptability Questionnaire, were examined. RESULTS: Low study drop out (30% of enrolled participants; 14% of participants who began the intervention) and high attendance rates were observed. Caregivers found sessions related to common, everyday interactions most helpful. Adolescents indicated sessions related to having get-togethers and social nuances (e.g., humor) as most helpful. Caregiver ratings indicated acceptability of the intervention. CONCLUSIONS: This investigation supported the feasibility and acceptability of telehealth PEERS®, a social skills intervention program, among adolescents with NF1 and their caregivers based on attendance patterns as well as appraisal of the curriculum and telehealth modality.

Longitudinal Investigation of Early Motor Development in Neurofibromatosis Type 1.

OBJECTIVE: Research indicates that children with neurofibromatosis type 1 (NF1) have weaknesses in fine and gross motor development in early childhood; however, little is known about the stability and developmental trajectory of motor functioning. We investigated (1) whether motor difficulties are evident and stable in the preschool period in children with NF1 and (2) whether there are particular patterns of motor development in this population. METHODS: Participants with NF1 and a control group of unaffected siblings were enrolled at ages 3-8 years and were assessed yearly. Motor functioning was assessed longitudinally using the Scales of Independent Behavior-Revised Motor Scale and the Differential Ability Scales-II Copying subtest. Wilcoxon sign tests were used to compare motor functioning at 3 or 4 years to 5 or 6 years old for children with NF1 seen during both time periods (N = 27). Linear mixed model growth curve analyses were used to compare trajectories for both children with NF1 (N = 62) and unaffected siblings (N = 37). RESULTS: Children with NF1 made relative gains in raw scores, but not standard scores, across measures. Growth curve analyses revealed a significant effect of NF1 status on gross motor, fine motor, and copying scores, as well as an age by NF1 status effect on fine and gross motor scores. CONCLUSIONS: Motor difficulties are evident early in life in children with NF1. Though children with NF1 clearly acquire motor skills over time, they continue to fall behind unaffected siblings, with the gap potentially widening over time. Further implications are discussed.

Parent and Teacher Perspectives on Emerging Executive Functioning in Preschoolers With Neurofibromatosis Type 1: Comparison to Unaffected Children and Lab-Based Measures.

Objective: Children with neurofibromatosis type 1 (NF1) are at risk for executive functioning (EF) challenges, with little research with preschoolers. Methods: EF was examined using parent and teacher ratings of preschool-aged children with NF1 ( n = 26) and parent ratings of unaffected children ( n = 37) on the Behavior Rating Inventory for Executive Functioning-Preschool Form. Relations to performance on laboratory measures were also examined. Results: Based on parent ratings, children with NF1 had more dysfunction than the normative mean on the Working Memory (WM) scale and Emergent Metacognition Index (EMI). Teacher ratings indicated greater dysfunction than the normative mean on the WM and Planning/Organization scales, EMI, and General Executive Composite. Children with NF1 showed more difficulties than unaffected children on the WM scale. Teacher report of WM was significantly correlated with Differential Ability Scales-Second Edition Digits Forward performance. Conclusions: WM emerged as an area of difficulty for young children with NF1.

7q11.23 Duplication syndrome: Physical characteristics and natural history.

In order to describe the physical characteristics, medical complications, and natural history of classic 7q11.23 duplication syndrome [hereafter Dup7 (MIM 609757)], reciprocal duplication of the region deleted in Williams syndrome [hereafter WS (MIM 194050)], we systematically evaluated 53 individuals aged 1.25-21.25 years and 11 affected adult relatives identified in cascade testing. In this series, 27% of probands with Dup7 had an affected parent. Seven of the 26 de novo duplications that were examined for inversions were inverted; in all seven cases one of the parents had the common inversion polymorphism of the WS region. We documented the craniofacial features of Dup7: brachycephaly, broad forehead, straight eyebrows, broad nasal tip, low insertion of the columella, short philtrum, thin upper lip, minor ear anomalies, and facial asymmetry. Approximately 30% of newborns and 50% of older children and adults had macrocephaly. Abnormalities were noted on neurological examination in 88.7% of children, while 81.6% of MRI studies showed structural abnormalities such as decreased cerebral white matter volume, cerebellar vermis hypoplasia, and ventriculomegaly. Signs of cerebellar dysfunction were found in 62.3%, hypotonia in 58.5%, Developmental Coordination Disorder in 74.2%, and Speech Sound Disorder in 82.6%. Behavior problems included anxiety disorders, ADHD, and oppositional disorders. Medical problems included seizures, 19%; growth hormone deficiency, 9.4%; patent ductus arteriosus, 15%; aortic dilation, 46.2%; chronic constipation, 66%; and structural renal anomalies, 18%. We compare these results to the WS phenotype and offer initial recommendations for medical evaluation and surveillance of individuals who have Dup7.

Children with 7q11.23 duplication syndrome: psychological characteristics.

To begin to delineate the psychological characteristics associated with classic 7q11.23 duplication syndrome (duplication of the classic Williams syndrome region; hereafter classic Dup7), we tested 63 children with classic Dup7 aged 4-17 years. Sixteen toddlers aged 18-45 months with classic Dup7 and 12 adults identified by cascade testing also were assessed. For the child group, median General Conceptual Ability (similar to IQ) on the Differential Ability Scales-II was 85.0 (low average), with a range from severe disability to high average ability. Median reading and mathematics achievement standard scores were at the low average to average level, with a range from severe impairment to high average or superior ability. Adaptive behavior was considerably more limited; median Scales of Independent Behavior-Revised Broad Independence standard score was 62.0 (mild impairment), with a range from severe adaptive impairment to average adaptive ability. Anxiety disorders were common, with 50.0% of children diagnosed with Social Phobia, 29.0% with Selective Mutism, 12.9% with Separation Anxiety Disorder, and 53.2% with Specific Phobia. In addition, 35.5% were diagnosed with Attention Deficit/Hyperactivity Disorder and 24.2% with Oppositional Defiant Disorder or Disruptive Behavior Disorder-Not Otherwise Specified. 33.3% of the children screened positive for a possible Autism Spectrum Disorder and 82.3% were diagnosed with Speech Sound Disorder. We compare these findings to previously reported results for children with Williams syndrome and argue that genotype/phenotype studies involving the Williams syndrome region offer important opportunities to understand the contribution of genes in this region to common disorders affecting the general population.

Cognitive and psychosocial phenotype of young children with neurofibromatosis-1.

Children with neurofibromatosis-1 (NF1), a neurodevelopmental disorder resulting from a mutation of the NF1 gene (17q11.2), often have difficulties with learning and attention, but there is little research in the early childhood years. In this study, the cognitive and psychosocial functioning of 40 young children with NF1 (ages 3 through 6) was examined and compared both to normative data and to a contrast group comprised of unaffected siblings and community members matched for age and socio-economic status (n = 37). Children with NF1 showed significantly weaker cognitive abilities across all domains and for the vast majority of subtests. Consistent with research in older children, a variety of patterns of intra-individual strength and weakness were present for young children with NF1. Few significant group differences in psychosocial functioning were observed, but the children with NF1 showed significantly greater functional communication problems than did the unaffected group. Overall, the results indicate that in participant groups matched for age and socioeconomic status, cognitive vulnerabilities are evident for close to half of young children with NF1, with some relations to psychosocial functioning, particularly functional communication, attention problems and social skills.

Pilot study of the effectiveness of a telehealth group for improving peer relationships for adolescents with neurofibromatosis type 1.

BACKGROUND: Interventions for social difficulties have not been investigated in the neurofibromatosis type 1 (NF1) population despite observations of elevated rates of social difficulties. In this pilot study, the effectiveness of a 14-week telehealth PEERS® intervention with nineteen adolescents with NF1 (Mage=13.79 years, SD = 1.32) with social skills difficulties was examined. Measures of social outcomes were completed at three timepoints (before, immediately after, and at 14-week follow-up). RESULTS: Caregiver-reported social-emotional skills, social impairment, caregiver-reported number of adolescent get-togethers, and teen social knowledge showed significant improvement following the intervention. CONCLUSIONS: The PEERS® intervention is promising to support the social and friendship skills of adolescents with NF1 who have social difficulties.

An evaluation of computerized attention and executive function measures for use with school age children with neurofibromatosis type 1.

The present study investigated the performance of children with neurofibromatosis type 1 on computerized assessments of attention and executive function. Relations to ADHD symptomatology were also examined. Participants included 37 children (20 male) with NF1 (9-13 years; Mage = 11.02). Participants completed the NIH Toolbox Dimensional Change Card Sort, List Sort Working Memory (LSWM), and Flanker tasks, as well as Cogstate Identification and One Back tests. ADHD symptomatology was assessed using the K-SADS. Average performance was significantly different from the normative mean on every measure, except LSWM. The NIH Toolbox Flanker and Cogstate Identification tasks detected the highest proportion of participants with at least mild difficulty, and the Cogstate Identification task detected the highest proportion of participants with severe difficulty. Analyses revealed significant relations with ADHD symptomatology for two NIH toolbox tasks. The various computerized measures of attention and executive function offer different information when working with school age children with NF1. The NIH Flanker may offer the most room for change and offers face validity, which may be beneficial for clinical trials research. However, the LSWM shows most support for relations with behavioral indicators of attention and executive challenges.

Addressing fears of children with Williams syndrome: therapist and child behavior in the context of a novel play-and humor-infused exposure therapy approach.

Many children with Williams syndrome struggle with fears and phobias that significantly impact their daily lives. Yet, there is sparse literature about the impact of behavioral interventions to treat anxiety and phobias among children with Williams syndrome. Using observational coding of intervention videos, the current study examines patterns of the therapist's use of play and humor and relations to child behavioral responses for four children with Williams syndrome who were identified as treatment responders to humor- and play-infused exposure therapy for fears and anxieties. Sessions were coded for therapist behaviors (exposure with or without play/humor, stimulus type used during exposure, passive or invited attention to feared stimulus, and spontaneous parent participation in exposure) as well as positive, negative, and neutral child behaviors (verbalizations and behaviors). Temporal patterns between therapist and child behaviors were analyzed using lag sequential analyses. The results showed that tolerance of feared stimuli improved for two of the four children following this play- and humor-infused exposure therapy approach, and the remaining two participants demonstrated progress beyond tolerating the feared stimulus and showed increased positive behaviors with the feared stimulus across sessions. Findings also showed patterns of therapist attunement to the child's anxiety level demonstrated through efforts to flexibly adjust the degrees of exposure. Therapist-initiated invited attention behaviors, indicative of the therapist's use of narration and priming, were associated with child tolerance and positive behaviors during exposure to the feared stimulus. Limitations of this study include a very small sample size, short duration of intervention, and a single-subject research design, which limit the generalizability of findings. Implications and future directions of this research are discussed.

Relations Between Selective Mutism and Speech Sound Disorder in Children With 7q11.23 Duplication Syndrome.

PURPOSE: The aim of this study was to explore relations between speech sound disorder severity and selective mutism in a group of children with 7q11.23 duplication syndrome (Dup7), a genetic condition predisposing children to childhood apraxia of speech (CAS) and other speech sound disorders and to anxiety disorders, including selective mutism and social anxiety disorder. METHOD: Forty-nine children aged 4-17 years with genetically confirmed Dup7 completed the Goldman-Fristoe Test of Articulation-Second Edition (GFTA-2), the Expressive Vocabulary Test-Second Edition (EVT-2), and the Differential Ability Scales-Second Edition (DAS-II). Parents completed the Anxiety Disorders Interview Schedule-Parent (ADIS-P). RESULTS: Mean standard scores (SSs) were 65.67 for the GFTA-2, 92.73 for the EVT-2, and 82.69 for the DAS-II General Conceptual Ability (GCA; similar to IQ). Standard deviations for all measures were larger than for the general population. GFTA-2 SS was significantly correlated with both EVT-2 SS and DAS-II GCA. Based on the ADIS-P, 22 participants (45%) were diagnosed with selective mutism and 29 (59%) were diagnosed with social anxiety disorder. No significant differences in performance on any of the measures were found either between the group with a selective mutism diagnosis and the group that did not have selective mutism or between the group with a selective mutism and/or social anxiety disorder diagnosis and the group that did not have either disorder. CONCLUSIONS: For children with Dup7, neither the diagnosis of selective mutism nor the diagnosis of selective mutism and/or social anxiety disorder was related to severity of speech sound disorder, expressive vocabulary ability, or overall intellectual ability. Accordingly, treatment for speech sound disorder alone is unlikely to lead to remission of selective mutism or social anxiety disorder. Instead, selective mutism and/or social anxiety disorder should be treated directly. Further research is needed to determine if these findings generalize to other populations, such as children with idiopathic CAS.

DNA methylation profiles in individuals with rare, atypical 7q11.23 CNVs correlate with GTF2I and GTF2IRD1 copy number.

Williams-Beuren syndrome (WBS) and 7q11.23 duplication syndrome (Dup7) are rare neurodevelopmental disorders caused by deletion and duplication of a 1.5 Mb region that includes at least five genes with a known role in epigenetic regulation. We have shown that CNV of this chromosome segment causes dose-dependent, genome-wide changes in DNA methylation, but the specific genes driving these changes are unknown. We measured genome-wide whole blood DNA methylation in six participants with atypical CNV of 7q11.23 (three with deletions and three with duplications) using the Illumina HumanMethylation450k array and compared their profiles with those from groups of individuals with classic WBS or classic Dup7 and with typically developing (TD) controls. Across the top 1000 most variable positions we found that only the atypical rearrangements that changed the copy number of GTF2IRD1 and/or GTF2I (coding for the TFII-IRD1 and TFII-I proteins) clustered with their respective syndromic cohorts. This finding was supported by results from hierarchical clustering across a selection of differentially methylated CpGs, in addition to pyrosequencing validation. These findings suggest that CNV of the GTF2I genes at the telomeric end of the 7q11.23 interval is a key contributor to the large changes in DNA methylation that are seen in blood DNA from our WBS and Dup7 cohorts, compared to TD controls. Our findings suggest that members of the TFII-I protein family are involved in epigenetic processes that alter DNA methylation on a genome-wide level.

Anxiety, concerns and COVID-19: Cross-country perspectives from families and individuals with neurodevelopmental conditions.

Background: The COVID-19 pandemic had a major impact on the mental health and well-being of children with neurodevelopmental conditions (NDCs) and of their families worldwide. However, there is insufficient evidence to understand how different factors (e.g., individual, family, country, children) have impacted on anxiety levels of families and their children with NDCs developed over time. Methods: We used data from a global survey assessing the experience of 8043 families and their children with NDCs (mean of age (m) = 13.18 years, 37% female) and their typically developing siblings (m = 12.9 years, 45% female) in combination with data from the European Centre for Disease Prevention and Control, the University of Oxford, and the Central Intelligence Agency (CIA) World Factbook, to create a multilevel data set. Using stepwise multilevel modelling, we generated child-, family- and country-related factors that may have contributed to the anxiety levels of children with NDCs, their siblings if they had any, and their parents. All data were reported by parents. Results: Our results suggest that parental anxiety was best explained by family-related factors such as concerns about COVID-19 and illness. Children's anxiety was best explained by child-related factors such as children's concerns about loss of routine, family conflict, and safety in general, as well as concerns about COVID-19. In addition, anxiety levels were linked to the presence of pre-existing anxiety conditions for both children with NDCs and their parents. Conclusions: The present study shows that across the globe there was a raise in anxiety levels for both parents and their children with NDCs because of COVID-19 and that country-level factors had little or no impact on explaining differences in this increase, once family and child factors were considered. Our findings also highlight that certain groups of children with NDCs were at higher risk for anxiety than others and had specific concerns. Together, these results show that anxiety of families and their children with NDCs during the COVID-19 pandemic were predicted by very specific concerns and worries which inform the development of future toolkits and policy. Future studies should investigate how country factors can play a protective role during future crises.

The Behavioral Phenotype of 7q11.23 Duplication Syndrome Includes Risk for Oppositional Behavior and Aggression.

OBJECTIVE: 7q11.23 duplication syndrome (Dup7) is a genetic disorder with a variable phenotype associated with cognitive and behavioral characteristics including a high incidence of expressive language difficulties, social anxiety, and oppositional or disruptive behavior. Correlates of aggression and oppositionality were examined. METHOD: Participants were 63 children with genetically confirmed Dup7 between the ages of 4 and 17 years. A multimethod, multi-informant approach was used to assess aggression and oppositional behavior, and the contributions of cognitive functioning, expressive language, autism spectrum, social anxiety, and hyperactivity/impulsivity (H/I) symptomatology were considered. RESULTS: Elevated levels of aggression and oppositional behavior were found. Cognitive functioning, expressive language, and autism spectrum disorder symptomatology were not significantly related to parent ratings of aggression, although young children who had language and nonverbal cognitive delays were most likely to demonstrate examiner-observed aggression. Social anxiety and H/I symptomatology were related to defiant/aggressive and oppositional behavior. CONCLUSION: Genes in the 7q11.23 region duplicated in Dup7, in transaction with the environment, may contribute to aggressive and oppositional behavior.

Patterns of performance of children with neurofibromatosis type 1 on the K-CPT and K-CPT 2.

Children with neurofibromatosis type 1 (NF1) often have attention difficulties with emerging evidence that these difficulties can be seen even in early childhood. This study aimed to explore the relative utility of two versions of a commonly used computerized attention measure for young children with NF1 and to explore relations with parent-reported attention in young children with NF1. Two independent samples of young children with NF1 participated. One sample (Study 1; N = 22; Mage = 4.95 (SD = 0.66)) completed the Conner's Kiddie Continuous Performance Test (K-CPT). A second and separate sample (Study 2; N = 19; Mage = 5.46 (SD = 0.74)) completed the K-CPT second edition (K-CPT 2). Relations of the K-CPT and K-CPT 2 with concurrent parent-reported attention (Kiddie Disruptive Behavior Disorder Schedule; Conners parent report questionnaires) were explored. The K-CPT sample's scores significantly differed from the normative median on Commissions, Hit Rate Standard Error, Variability, Detectability, Perseverations, and Hit Rate Inter Stimulus Interval. No relations with parent-report were identified. The K-CPT 2 sample's scores were significantly worse than normative data on every score except Hit Rate Block Change. Multiple scores on the K-CPT 2 were significantly related to parent-report of inattention and hyperactivity with some evidence of construct validity for the distinction between inattention and hyperactivity. The K-CPT 2 may be more useful for the assessment of attention problems in young children with NF1 as more challenges were observed and performance was more closely related to parent-reported attention difficulties than its predecessor the K-CPT.

Psychometric Properties of Attention Measures in Young Children with Neurofibromatosis Type 1: Preliminary Findings.

Children with neurofibromatosis type 1 (NF1) often demonstrate difficulties with attention and executive functioning that can be evident starting at a young age. There has been little research about which measures of attention are most suitable for use with young children with NF1. This pilot study explored several computerized measures of attention, a digits forward task, and parent report measures of attention to compare their reliability, validity, and the degree to which they capture attention difficulty in this population. Participants with NF1 ages 4 to 6 years were seen for one (n=2) or two (n=18) time points. Statistical analyses for evaluating evidence for test-retest reliability, convergent and discriminant validity, practice effects, and identification of difficulties were conducted. Each measure demonstrated relative strengths and weaknesses, and there may not be a "one size fits all" measure for use with young children with NF1. However, the Behavior Rating Inventory of Executive Function Preschool/Second Edition, Conners Early Childhood Inattention/Hyperactivity Scale, and the Conners Kiddie Continuous Performance Test Second Edition generally had the highest reliability and most evidence of validity. More specific recommendations are provided for the appropriate measure to use in clinical and research batteries.

Parent-Reported Social Skills in Children with Neurofibromatosis Type 1: Longitudinal Patterns and Relations with Attention and Cognitive Functioning.

OBJECTIVE: Social skills difficulties are commonly reported by parents and teachers of school age (SA) children with neurofibromatosis type 1 (NF1). Investigations of social skills of young children with NF1 are scarce. This study aimed to characterize the emergence of social skills challenges beginning in early childhood, examine social skills longitudinally into SA, and explore interrelations with attention-deficit hyperactivity disorder (ADHD) symptomatology and cognitive functioning among children with NF1 cross-sectionally and longitudinally. METHOD: Three samples of children with NF1 and their parents participated: (1) early childhood (n = 50; ages 3-6; mean [M] = 3.96, SD = 1.05), (2) SA (n = 40; ages 9-13; [M] = 10.90, SD = 1.59), and (3) both early childhood and SA (n = 25). Parent-reported social skills (Social Skills Rating System and Social Skills Improvement System), ADHD symptomatology (Conners Parent Rating Scales - Revised and Conners - Third Edition), and parent-reported cognitive abilities (Differential Ability Scales - Second Edition) were evaluated. RESULTS: Parental ratings of social skills were relatively stable throughout childhood. Ratings of social skills at the end of early childhood significantly predicted school-age social skills. Parental ratings of ADHD symptomatology showed significant negative relations with social skills. Early childhood inattentive symptoms predicted school-age social skills ratings. Cognitive functioning was not significantly related to social skills. CONCLUSION: Parent-reported social skills difficulties are evident during early childhood. This work adds to the literature by describing the frequency and stability of social skills challenges in early childhood and in the school-age period in NF1. Research about interventions to support social skills when difficulties are present is needed.

Recommendations for Measurement of Attention Outcomes in Preschoolers With Neurofibromatosis.

Children with neurofibromatosis type 1 (NF1) are at increased risk for attention problems. While most research has been conducted with school-aged cohorts, preschool-aged children offer a novel developmental window for clinical studies, with the promise that treatments implemented earlier in the developmental trajectory may most effectively modify risk for later difficulties. Designing research studies around the youngest children with NF1 can result in intervention earlier in the developmental cascade associated with NF1 gene abnormalities. Furthermore, clinical trials for medications targeting physical and psychological aspects of NF1 often include individuals spanning a wide age range, including preschool-aged children. In a prior report, the REiNS Neurocognitive Subcommittee made recommendations regarding performance-based and observer-rated measures of attention for use in clinical trials and highlighted the need for separate consideration of assessment methods for young children. The observer-rated Attention-Deficit/Hyperactivity Disorder Rating Scale-Preschool version is recommended as a primary outcome measure. The NIH Toolbox Flanker, Dimensional Change Card Sort, and List Sort Working Memory tasks and Digits Forward from the Differential Ability Scales-2nd Edition (performance-based measures) are recommended as secondary outcome measures. Specific methodologic recommendations for inclusion of preschoolers in clinical trials research are also offered.

The impact of the COVID-19 pandemic on neurofibromatosis clinical care and research.

PURPOSE: The coronavirus disease 2019 (COVID-19) pandemic has had unprecedented impact on the provision of medical care for genetic disorders. The purpose of this study was to assess the effects of the pandemic on neurofibromatosis (NF) care and research. METHODS: Sixty-three United States NF clinics were surveyed to identify the impact of the pandemic on clinician role, patient volume, continuity of guideline-driven surveillance, research protocols, and use of (and satisfaction with) telehealth for the delivery of NF care. RESULTS: Fifty-two clinic directors or their representatives completed the survey (83% response rate). About 2/3 of the clinics reported a greater than 50% decrease in the number of available patient appointments, and modified clinical surveillance and research protocols. Fifty-one clinics (98%) newly instituted telehealth during the pandemic. Barriers to telehealth prior to the pandemic were insurance reimbursement concerns and lack of infrastructure. Since telehealth was initiated, high provider satisfaction was reported with ease of use. The most common area of concern was related to inability to perform a physical examination. CONCLUSION: Results show marked impacts on NF care and research since the beginning of the pandemic, with potential long-term changes related to the introduction (or adoption) of telehealth for clinical care.