Review
Biochemistry & Molecular Biology
Ryota Tamura
Summary: Neurofibromatosis is a neurocutaneous syndrome characterized by tumors in the nervous system, with NF1, NF2, and SWN as its three main types. While NF1 and NF2 have known genetic mutations and targeted therapies, the molecular mechanisms of SWN remain unclear and require further research.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Clinical Neurology
Cathal John Hannan, Charlotte Hammerbeck-Ward, Omar Nathan Pathmanaban, Miriam J. Smith, Scott A. A. Rutherford, Simon K. K. Lloyd, Simon Richard Mackenzie Freeman, Andrew J. Wallace, Andrew Thomas King, Dafydd Gareth Richard Evans
Summary: Patients presenting with unilateral vestibular schwannomas (UVS) and multiple meningiomas (MM) are more likely to be diagnosed with neurofibromatosis type 2 (NF2) compared to patients with UVS and multiple nonintradermal schwannomas (NIDS), but less likely to develop bilateral vestibular schwannomas. Some patients with MM without meeting NF2 criteria have pathogenic variants in SMARCE1 and mosaic NF2.
Article
Genetics & Heredity
Scott R. Plotkin, Ludwine Messiaen, Eric Legius, Patrice Pancza, Robert A. Avery, Jaishri O. Blakeley, Dusica Babovic-Vuksanovic, Rosalie Ferner, Michael J. Fisher, Jan M. Friedman, Marco Giovannini, David H. Gutmann, Clemens Oliver Hanemann, Michel Kalamarides, Hildegard Kehrer-Sawatzki, Bruce R. Korf, Victor-Felix Mautner, Mia MacCollin, Laura Papi, Katherine A. Rauen, Vincent Riccardi, Elizabeth Schorry, Miriam J. Smith, Anat Stemmer-Rachamimov, David A. Stevenson, Nicole J. Ullrich, David Viskochil, Katharina Wimmer, Kaleb Yohay, Susan M. Huson, Pierre Wolkenstein, D. Gareth Evans
Summary: The study aims to update the diagnostic criteria for neurofibromatosis type 2 (NF2) and schwannomatosis (SWN) by incorporating recent advances in genetics, ophthalmology, neuropathology, and neuroimaging. The updated criteria include clinical features and genetic testing, emphasizing the phenotypic overlap between the two conditions.
GENETICS IN MEDICINE
(2022)
Article
Genetics & Heredity
Jineta Banerjee, Jan M. Friedman, Laura J. Klesse, Kaleb H. Yohay, Justin T. Jordan, Scott R. Plotkin, Robert J. Allaway, Jaishri O. Blakeley
Summary: This study investigated whether patients with rare diseases such as neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2), or schwannomatosis (SWN) are more susceptible to SARS-CoV-2 infection and severe COVID-19. The results showed that the proportion of positive cases in NF1, NF2, or SWN patients was not significantly higher than in individuals without these rare diseases. There were no severe outcomes reported in the NF2 or SWN cohorts, and the proportion of severe outcomes in NF1 patients was similar to other rare disease cohorts and the general population.
GENETICS IN MEDICINE
(2023)
Article
Clinical Neurology
Heather L. Thompson, Ann Blanton, Barbara Franklin, Vanessa L. Merker, Kevin H. Franck, D. Bradley Welling, REiNS Int Collaboration
Summary: The REiNS recommends the use of the "Self-Assessment of Communication" adult and adolescent forms for assessing patient-reported hearing function and hearing-related quality of life for NF2 clinical trials, further work is needed to demonstrate the utility of these measures in evaluating pharmacologic or behavioral interventions.
Article
Clinical Neurology
Heather L. Thompson, Ann Blanton, Barbara Franklin, Vanessa L. Merker, Kevin H. Franck, D. Bradley Welling
Summary: The study systematically evaluated published patient-reported outcome measures for hearing function and hearing-related quality of life, recommending specific measures for use in NF2 clinical trials. Measures were selected based on participant characteristics, item content, psychometric properties, and feasibility for use in clinical trials. Further research is needed to demonstrate the utility of these measures in evaluating interventions.
Article
Psychology, Multidisciplinary
Anna Leidger, Marie Vosschulte, Timo O. Nieder, Victor-Felix Mautner
Summary: This study investigated the relationship between skin tumors, sexuality, and psychosocial factors in individuals with NF1. The results showed a significant correlation between sexuality, mental health, and depressive symptoms in NF1 patients.
FRONTIERS IN PSYCHOLOGY
(2022)
Review
Clinical Neurology
Simge Acar, Edwin Nieblas-Bedolla, Amy E. Armstrong, Angela C. Hirbe
Summary: Recent and ongoing clinical trials have mainly focused on patients with NF1 and the treatment of PNs. This research has resulted in the first FDA-approved drug for NF1-PN and has changed the approach to managing these tumors, allowing for systemic therapy instead of relying solely on surgery. Trials evaluating comorbid psychiatric conditions and quality of life among NF patients appear to be less common. These areas may require more attention in future studies to enhance clinical management.
PEDIATRIC NEUROLOGY
(2022)
Article
Clinical Neurology
Sulaman Durrani, William Mualem, Ali Shoushtari, Karim Rizwan Nathani, Mohamad Bydon
Summary: This study provides a quantitative analysis of the historical and current state of academic efforts regarding neurofibromatosis (NF). The findings reveal a shift towards targeted therapies focusing on specific pathways involved in tumorigenesis and highlight the top 20 genetic and molecular pathways associated with NF.
WORLD NEUROSURGERY
(2022)
Article
Genetics & Heredity
Jane Fleming, Oliver Morgan, Claire Wong, Timothy E. E. Schlub, Yemima Berman
Summary: This study reveals the impact of NF1-related itch and visibility on adults and children, as well as the need for treatment to improve appearance and relieve itching. The findings emphasize the importance of raising awareness about NF1 and providing management and treatment options for adults.
MOLECULAR GENETICS & GENOMIC MEDICINE
(2023)
Article
Genetics & Heredity
Vanessa L. Merker, Pamela Knight, Heather B. Radtke, Kaleb Yohay, Nicole J. Ullrich, Scott R. Plotkin, Justin T. Jordan
Summary: This study evaluated the level of awareness of and agreement with published neurofibromatosis (NF) clinical guidelines among NF specialists in the United States. The results showed wide variability in both awareness of and agreement with the guidelines among the experts. Future quality improvement efforts should focus on evidence-based, consensus-driven methods to update and disseminate these guidelines to support collaboration among this multi-specialty group of providers.
ORPHANET JOURNAL OF RARE DISEASES
(2022)
Article
Genetics & Heredity
Anna Cecilia Lawson McLean, Anna Freier, Aaron Lawson McLean, Johannes Kruse, Steffen Rosahl
Summary: This study aimed to develop and validate the NFTI-QOL-D questionnaire and correlate QOL scores with depression scores and clinical disease severity in German-speaking NF2 patients. The results showed that the NFTI-QOL-D is a reliable and useful tool for assessing quality of life in German-speaking NF2 patients.
ORPHANET JOURNAL OF RARE DISEASES
(2023)
Review
Genetics & Heredity
Cristina Perez-Becerril, D. Gareth Evans, Miriam J. Smith
Summary: NF1, NF2, and schwannomatosis are genetic disorders predisposing to nerve sheath tumors, with pathogenic variants located in different genes. While most pathogenic variants can be identified through genetic screening, a proportion of cases remain undetected, especially in schwannomatosis.
Review
Medicine, General & Internal
Gaetano Magro, Giuseppe Broggi, Giuseppe Angelico, Lidia Puzzo, Giada Maria Vecchio, Valentina Virzi, Lucia Salvatorelli, Martino Ruggieri
Summary: Peripheral nerve sheath tumors include a range of lesions with different biological behavior, such as neurofibromas, schwannomas, and perineuriomas. These tumors can occur as isolated lesions or in association with other neurofibromatosis or schwannomatosis. Malignant peripheral nerve sheath tumors are soft tissue sarcomas that may arise from a peripheral nerve or pre-existing neurofibromas.
Article
Oncology
Isabel Gugel, Florian Grimm, Marcos Tatagiba, Martin U. Schuhmann, Julian Zipfel
Summary: Resection of peripheral and intraspinal schwannomas is an effective and low-risk treatment in both NF2 and SWNT. Patients with severe pain have a particular benefit from surgical treatment. Intraspinal lesions are associated with worse neurological function whereas peripheral lesions showed a higher pain intensity.
JOURNAL OF NEURO-ONCOLOGY
(2022)
Article
Genetics & Heredity
Pamela L. Wolters, Stephanie Reda, Staci Martin, Nour Al Ghriwati, Melissa Baker, Dale Berg, Gregg Erickson, Barbara Franklin, Vanessa L. Merker, Beverly Oberlander, Stephanie Reeve, Claas Rohl, Tena Rosser, Mary Anne Toledo-Tamula, Ana-Maria Vranceanu
Summary: The survey found that NF patients experienced higher levels of anxiety and stress during the COVID-19 pandemic, especially those with mental health disorders or severe NF symptoms. Although telehealth services were helpful, they were underutilized, indicating a need for increased awareness and utilization of these services.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2022)
Article
Genetics & Heredity
Vanessa L. Merker, Pamela Knight, Heather B. Radtke, Kaleb Yohay, Nicole J. Ullrich, Scott R. Plotkin, Justin T. Jordan
Summary: This study evaluated the level of awareness of and agreement with published neurofibromatosis (NF) clinical guidelines among NF specialists in the United States. The results showed wide variability in both awareness of and agreement with the guidelines among the experts. Future quality improvement efforts should focus on evidence-based, consensus-driven methods to update and disseminate these guidelines to support collaboration among this multi-specialty group of providers.
ORPHANET JOURNAL OF RARE DISEASES
(2022)
Article
Genetics & Heredity
Rebecca Burns, Kristin Niendorf, Kathleen Steinberg, Amy Mueller, Ina Ly, Justin T. Jordan, Scott R. Plotkin, Stephanie R. Hicks
Summary: This study compared the efficacy of germline-only versus paired genetic testing in clarifying the diagnosis of patients with features of NF2 and SWN. The results showed that paired testing had a higher likelihood of providing diagnostic clarity, especially for patients who had analysis of multiple tumors.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2022)
Article
Hematology
Matthew J. Frigault, Jorg Dietrich, Kathleen Gallagher, Mark Roschewski, Justin T. Jordan, Deborah Forst, Scott R. Plotkin, Daniella Cook, Keagan S. Casey, Kevin A. Lindell, Gabriel D. Depinho, Katelin Katsis, Eva Lynn Elder, Mark B. Leick, Bryan Choi, Nora Horick, Frederic Preffer, Meredith Saylor, Steven McAfee, Paul O'Donnell, Thomas R. Spitzer, Bimalangshu Dey, Zachariah DeFilipp, Areej El-Jawahri, Tracy T. Batchelor, Marcela Maus, Yi-Bin Chen
Summary: This study conducted a clinical trial of tisagenlecleucel in highly refractory patients with primary central nervous system lymphoma (PCNSL). The results showed that most patients responded well to the treatment and there were no severe side effects. This suggests that tisagenlecleucel is safe and effective in this patient population.
Article
Health Care Sciences & Services
Vanessa L. Merker, Justeen K. Hyde, Abigail Herbst, Amanda K. Solch, David C. Mohr, Lauren Gaj, Kelly Dvorin, Eileen M. Dryden
Summary: This study explores the impacts of engaging patients as consultants in research at a Veterans Health Administration research center. It found that patient engagement improved the quality and relevance of research studies, and had personal benefits for both researchers and patients.
JOURNAL OF GENERAL INTERNAL MEDICINE
(2022)
Article
Genetics & Heredity
Vanessa L. Merker, Bronwyn Slobogean, Justin T. Jordan, Shannon Langmead, Mark Meterko, Martin P. Charns, A. Rani Elwy, Jaishri O. Blakeley, Scott R. Plotkin
Summary: This study evaluated the extent and reasons for diagnostic delays and errors in schwannomatosis, a neurogenetic syndrome characterized by nerve sheath tumors and chronic pain. The results showed a long median time to diagnosis and a high misdiagnosis rate in patients with schwannomatosis. The study suggests that interventions in clinician education, genetic testing availability, expert review of pathology findings, and automatic triggers for genetics referrals may improve the diagnosis of schwannomatosis.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2022)
Article
Genetics & Heredity
Scott R. Plotkin, Ludwine Messiaen, Eric Legius, Patrice Pancza, Robert A. Avery, Jaishri O. Blakeley, Dusica Babovic-Vuksanovic, Rosalie Ferner, Michael J. Fisher, Jan M. Friedman, Marco Giovannini, David H. Gutmann, Clemens Oliver Hanemann, Michel Kalamarides, Hildegard Kehrer-Sawatzki, Bruce R. Korf, Victor-Felix Mautner, Mia MacCollin, Laura Papi, Katherine A. Rauen, Vincent Riccardi, Elizabeth Schorry, Miriam J. Smith, Anat Stemmer-Rachamimov, David A. Stevenson, Nicole J. Ullrich, David Viskochil, Katharina Wimmer, Kaleb Yohay, Susan M. Huson, Pierre Wolkenstein, D. Gareth Evans
Summary: The study aims to update the diagnostic criteria for neurofibromatosis type 2 (NF2) and schwannomatosis (SWN) by incorporating recent advances in genetics, ophthalmology, neuropathology, and neuroimaging. The updated criteria include clinical features and genetic testing, emphasizing the phenotypic overlap between the two conditions.
GENETICS IN MEDICINE
(2022)
Article
Clinical Neurology
K. Ina Ly, Vanessa L. Merker, Wenli Cai, Miriam A. Bredella, Alona Muzikansky, Raquel D. Thalheimer, Jennifer Liwei Da, Christina C. Orr, Hamilton P. Herr, Mary E. Morris, Connie Y. Chang, Gordon J. Harris, Scott R. Plotkin, Justin T. Jordan
Summary: The primary objective of this study was to evaluate the long-term growth behavior of internal neurofibromas in adults with NF1. The study found that internal neurofibroma growth behavior in older adults differs fundamentally from that in children and young adults, with most tumors demonstrating spontaneous shrinkage. Patient-specific, tumor-specific, and patient-reported variables were not strong predictors of tumor growth.
Article
Psychology, Educational
Stephanie L. Santoro, Maria J. Cabrera, Kelsey Haugen, Kavita Krell, Vanessa L. Merker
Summary: This study conducted virtual focus groups with 20 parents and 8 individuals with Down syndrome to gather their views on health indicators. The findings showed similarities in the perspectives of individuals with Down syndrome and their parents, with both groups discussing physical, mental, and social health components. However, individuals with Down syndrome provided a more limited range of examples with different nuances compared to parents.
JOURNAL OF APPLIED RESEARCH IN INTELLECTUAL DISABILITIES
(2023)
Article
Genetics & Heredity
Stephanie L. Santoro, Sandra Baker, Jasmine M. Blake, Maria J. Cabrera, Kelli Caughman, Jeanhee Chung, Sarah Cullen, Maureen Gallagher, Kelsey Haugen, Roxanne Hoke-Chandler, Kavita Krell, Julius Maina, Diana McLuckie, Vanessa L. Merker, Carie Michael, Kate O'Neill, Angeles Pena, Albert Pless Jr, Dina Royal, Michelle Slape, Noemi Alice Spinazzi, Amy Torres, Carlos G. Torres, Brian G. Skotko
Summary: This study utilized a mixed methods approach to investigate the impact of COVID-19 on health of individuals with Down syndrome (DS) and their families. Findings from virtual focus groups and a questionnaire revealed that the pandemic had negative effects on the physical, social, and mental health of individuals with DS and their parents. However, there were also unexpected positives, such as improved hygiene and opportunities for online learning and communication.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2023)
Article
Oncology
Scott R. Plotkin, Jeffrey Allen, Girish Dhall, Jian L. Campian, D. Wade Clapp, Michael J. Fisher, Rakesh K. Jain, James Tonsgard, Nicole J. Ullrich, Coretta Thomas, Lloyd J. Edwards, Bruce Korf, Roger Packer, Matthias A. Karajannis, Jaishri O. Blakeley
Summary: In this prospective multicenter phase II study, the efficacy, safety, and tolerability of bevacizumab for maintenance therapy in persons with NF2-SWN and hearing loss due to VS were evaluated. The results showed that maintenance bevacizumab (5 mg/kg every 3 weeks) was associated with high rates of hearing and tumor stability during 18 months of follow-up. No new unexpected adverse events related to bevacizumab were identified in this population.
Editorial Material
Medicine, Research & Experimental
Vanessa L. Merker, Andrea M. Gross, Brigitte C. Widemann, Scott R. Plotkin
Article
Genetics & Heredity
Jineta Banerjee, Jan M. Friedman, Laura J. Klesse, Kaleb H. Yohay, Justin T. Jordan, Scott R. Plotkin, Robert J. Allaway, Jaishri O. Blakeley
Summary: This study investigated whether patients with rare diseases such as neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2), or schwannomatosis (SWN) are more susceptible to SARS-CoV-2 infection and severe COVID-19. The results showed that the proportion of positive cases in NF1, NF2, or SWN patients was not significantly higher than in individuals without these rare diseases. There were no severe outcomes reported in the NF2 or SWN cohorts, and the proportion of severe outcomes in NF1 patients was similar to other rare disease cohorts and the general population.
GENETICS IN MEDICINE
(2023)
Article
Medicine, Research & Experimental
Pamela L. Wolters, Nour Al Ghriwati, Melissa Baker, Staci Martin, Dale Berg, Gregg Erickson, Barbara Franklin, Vanessa L. Merker, Beverly Oberlander, Stephanie Reeve, Claas Rohl, Tena Rosser, Ana-Maria Vranceanu
Summary: This study conducted the largest survey to assess physical symptoms, mental health needs, and preferences for psychosocial trials in adults with neurofibromatosis. The results indicate a high prevalence of disease manifestations, psychosocial difficulties, and untreated mental health problems in adults with neurofibromatosis. The study also found a high degree of willingness among participants to participate in psychosocial clinical trials. Patient preferences should be taken into consideration when designing and implementing psychosocial interventions to develop the most feasible and meaningful studies.
Meeting Abstract
Clinical Neurology
Vanessa L. Merker, Yidan Ma, Lori B. Chibnik, Nicole J. Ullrich, Kaleb H. Yohay, Pamela Knight, Heather B. Radtke, Scott R. Plotkin, Justin T. Jordan
ANNALS OF NEUROLOGY
(2022)
