1. Intro to FORWARD and FORWARD-MARCH
With Amie Milunovich
New results from the CDC-funded study, FORWARD, a natural history cohort of patients with Fragile X syndrome. Fragile X experts present the latest data on important topics such as aging in adults with FXS, medical problems in FXS, sensory problems in FXS, and behavioral subtypes in children with FXS.
Recording: 0:00-5:02
2. Adult Life in Fragile X Syndrome
With Elizabeth Berry-Kravis
This presentation characterizes transition services, employment and program participation, living arrangements, and engagement in social activities in adults with Fragile X syndrome enrolled in the FORWARD natural history database.
Recording: 5:09-15:32
3. Medical Problems in Fragile X Syndrome: Results from the FORWARD Project
With Nicole Tartaglia
This presentation describes what we’ve learned about medical problems in full mutation Fragile X syndrome using the results of the FORWARD project, including ear infections, seizures, GI problems, sleep apnea, musculoskeletal problems, and more. Data from males and females across different age groups are presented. We then use the results to provide a summary of current recommendations for medical screenings and treatments for medical care in Fragile X syndrome.
Recording: 15:38-33:09
4. Sensory Problems in Fragile X Syndrome
With Walter Kaufmann
Sensory symptoms, including increased reactivity to stimulation (hyperarousal), are common in children and adults with Fragile X syndrome. Despite their common occurrence, there is limited literature on the subject. For this reason, we decided to conduct the first comprehensive analysis of characteristics of sensory symptoms in children with FXS and their impact on families. For this purpose, we analyzed data from 933 children (720 boys, 213 girls) enrolled in the FORWARD project that included caregiver- and clinician-completed ad hoc and standardized questionnaires.
We found that more males than females were affected by sensory symptoms and hyperarousal (87% vs. 68% and 92% vs. 79%, respectively). The most common sensory symptom was difficulties with eye gaze, which increased with age in boys and girls. A strong sensory response was associated with more severe behavioral problems. As children with FXS age, their sensory symptoms are treated more with medications and less with occupational therapy or physical therapy. Sensory symptoms and hyperarousal were impactful since their severity predicted more severe disruptive behavior and less participation in everyday activities. We conclude that sensory symptoms are common and impactful problems in FXS, which deserve more research to improve their outcome.
Recording: 33:17-42:38
5. Behavioral Subtypes in Children With Fragile X Syndrome
With Walter Kaufmann
Children and adults with Fragile X syndrome are variably affected by the genetic disorder. This represents a challenge in determining the best treatment and prognosis for everyone with FXS. Although groups at each extreme of severity have been long recognized, until now there has not been a way to classify everyone with FXS. Therefore, we analyzed data on approximately 1,500 children from the FORWARD project using advanced statistical methods (latent class analysis) to identify different behavioral groups (subtypes). In these analyses, we incorporated multiple sources of behavioral data including all questionnaires completed by caregivers at FORWARD visits (SCQ, SRS-2, ABC). We found that the best classification includes five subtypes, one mild (31%), one severe (9%), and three moderate (32%, 7%, 20%) in severity. The latter groups differ in difficulties in social interaction and problem behavior. We conclude that the reported subtypes will be an asset for clinical research, including drug trials, and will also improve management in the clinic by providing a more personalized approach.
Recording: 42:49-53:50
About the Presenters
Amie Milunovich
Amie joined the NFXF in 2015. She holds a bachelor’s degree in family and consumer science and is a SOCRA-certified clinical research professional (CCRP). Amie has over 15 years of experience working in clinical research. She enjoys Bikram yoga, painting, cooking, and spending time with family and friends.
Elizabeth Berry-Kravis
Elizabeth Berry-Kravis, MD, PhD, established the Fragile X Clinic and Research Program at Rush University Medical Center in 1992. She studies Fragile X syndrome medical issues, epilepsy, and psychopharmacology and provides care to over 700 patients with FXS. She has been a leader in translational research, including the development of outcome measures and biomarkers, natural history studies, newborn screening, and particularly clinical trials of new targeted treatments.
Dr. Berry-Kravis’s laboratory studies the cellular roles of the Fragile X protein (FMRP), its relationship to phenotypes, and the optimization of genetic testing methods. She is a longstanding member of the NFXF Scientific and Clinical Advisory Committee, and Clinical Trials Committee, and is the principal investigator of the CDC-funded FORWARD-MARCH natural history project for Fragile X.
Dr. Berry-Kravis attended the University of Notre Dame for her undergraduate studies and the University of Chicago for her doctoral degrees (MD and PhD) and training in pediatric neurology.
Nicole Tartaglia
Nicole Tartaglia, MD, attended university and medical school at the University of Colorado. She completed her training in general pediatrics at Children’s Hospital Los Angeles, and fellowship training in developmental-behavioral pediatrics at the University of California Davis MIND Institute, where her research focused on children and adults with developmental disabilities, chromosomal abnormalities, Fragile X syndrome, and autism spectrum disorder. She also obtained her master’s in clinical investigation from the University of Colorado Graduate School.
Since 2007, Dr. Tartaglia has worked as faculty for the Colorado School of Medicine at Children’s Hospital Colorado in the Department of Pediatrics Section of Developmental Pediatrics, where she founded and directs the eXtraordinarY Kids Clinic for children and adolescents with sex chromosome disorders, and is also the director of the Denver Fragile X Clinic. In these clinics, she leads multidisciplinary teams that include medical providers, genetic counseling, psychology, speech-language therapy, occupational therapy, nursing, and social work, and collaborates extensively with community providers, therapists, and schools to provide optimal care for these special populations. She also evaluates and treats children with general developmental delays, autism spectrum disorder, ADHD, and other neurogenetic disorders.
Dr. Tartaglia has federally funded research projects evaluating natural history and outcome measures in sex chromosome disorders and Fragile X and collaborates with national networks of clinics to develop best practices for treatments of these conditions. She is also very active in clinical trials of targeted treatment medications for neurobehavioral features and developmental disabilities. Dr. Tartaglia is also a member of the NFXF’s Clinical Trials Committee.
Walter Kaufmann
Walter Kaufmann, MD, is a neurologist and adjunct professor in the Department of Human Genetics at Emory University School of Medicine. He is also the chief scientific officer at Anavex Life Sciences, a biopharmaceutical company. Dr. Kaufmann has over 20 years of experience in clinical research, focusing on developing novel therapies for genetic conditions associated with intellectual disability and neurologic disorders.
