المؤلفون: Line Kenborg, Susanne Oksbjerg Dalton, Elisabeth Wreford Andersen, Line Elmerdahl Frederiksen, John R. Østergaard, Jeanette Falck Winther, Karoline Doser, Jens Richardt Møllegaard Jepsen, Sven Asger Sørensen, John J. Mulvihill, Pernille Envold Bidstrup, Anne Katrine Duun-Henriksen, Christoffer Johansen, Vincent M. Riccardi, Anja Krøyer, Hanne Hove

المصدر: Kenborg, L, Andersen, E W, Duun-Henriksen, A K, Jepsen, J R M, Doser, K, Dalton, S O, Bidstrup, P E, Krøyer, A, Frederiksen, L E, Johansen, C, Østergaard, J R, Hove, H, Sørensen, S A, Riccardi, V M, Mulvihill, J J & Winther, J F 2021, ' Psychiatric disorders in individuals with neurofibromatosis 1 in Denmark : A nationwide register-based cohort study ', American Journal of Medical Genetics. Part A, vol. 185, no. 12, pp. 3706-3716 . https://doi.org/10.1002/ajmg.a.62436Test

مصطلحات موضوعية: Male, medicine.medical_specialty, Neurofibromatosis 1, Autism Spectrum Disorder, Denmark, Adjustment disorders, Population, International Classification of Diseases, Risk Factors, Intellectual Disability, neurofibromatosis 1, cohort study, Genetics, medicine, Humans, Psychiatric hospital, Child, Psychiatry, education, Genetics (clinical), Depression (differential diagnoses), Proportional Hazards Models, Depressive Disorder, education.field_of_study, business.industry, Mental Disorders, Infant, medicine.disease, population-based, Substance abuse, psychiatric disorders, Treatment Outcome, Psychotic Disorders, Attention Deficit Disorder with Hyperactivity, Schizophrenia, Child, Preschool, Cohort, Female, business, Cohort study

الوصف: The aim of this study was to assess the risks of psychiatric disorders in a large cohort of 905 individuals with NF1 and 7614 population comparisons matched on sex and year of birth. The cohort was linked to the Danish Psychiatric Central Research Register to ascertain information on hospital contacts for psychiatric disorders based on the International Classification of Diseases version 8 and 10. The hazard ratio (HR) for a first psychiatric hospital contact was higher in girls (4.19, 95% confidence interval [CI] 1.81–9.69) and boys with NF1 (5.02, 95% CI 3.27–7.69)

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0de89207fde3c02649bfb5efa7a1b0e6Test
https://doi.org/10.1002/ajmg.a.62436Test

المؤلفون: Beth Stronach, Lisa Schoyer, Dominic Esposito, Katherine A. Rauen, Edjay R. Hernandez, Leslie G. Biesecker, Bruce D. Gelb, Mignon L. Loh, Andrea M. Gross, Pamela L. Wolters, Deborah K. Morrison, Megan N. Frone, Frank McCormick, Karen W. Gripp, Eric Legius, Lisa Schill, Staci Martin, Sharon A. Savage, Marielle E. Yohe, Brigitte C. Widemann, Douglas R. Stewart, Dina Zand

المصدر: Am J Med Genet A

مصطلحات موضوعية: Heart Defects, Congenital, Research Report, Oncology, medicine.medical_specialty, Neurofibromatosis 1, Breakthrough therapy, RASopathy, Cardiofaciocutaneous syndrome, Article, Costello syndrome, Ectodermal Dysplasia, Internal medicine, Biomarkers, Tumor, Genetics, medicine, Humans, Molecular Targeted Therapy, Neurofibromatosis, Intersectoral Collaboration, Genetics (clinical), business.industry, Costello Syndrome, Noonan Syndrome, Facies, medicine.disease, National Cancer Institute (U.S.), United States, Failure to Thrive, Clinical trial, Mutation, ras Proteins, Selumetinib, Noonan syndrome, business, Signal Transduction

الوصف: RASopathies caused by germline pathogenic variants in genes that encode RAS pathway proteins. These disorders include neurofibromatosis type 1 (NF1), Noonan syndrome (NS), cardiofaciocutaneous syndrome (CFC), and Costello syndrome (CS), and others. RASopathies are characterized by heterogenous manifestations, including congenital heart disease, failure to thrive, and increased risk of cancers. Previous work led by the NCI Pediatric Oncology Branch has altered the natural course of one of the key manifestations of the RASopathy NF1. Through the conduct of a longitudinal cohort study and early phase clinical trials, the MEK inhibitor selumetinib was identified as the first active therapy for the NF1-related peripheral nerve sheath tumors called plexiform neurofibromas (PNs). As a result, selumetinib was granted breakthrough therapy designation by the FDA for the treatment of PN. Other RASopathy manifestations may also benefit from RAS targeted therapies. The overall goal of Advancing RAS/RASopathy Therapies (ART), a new NCI initiative, is to develop effective therapies and prevention strategies for the clinical manifestations of the non-NF1 RASopathies and for tumors characterized by somatic RAS mutations. This report reflects discussions from a February 2019 initiation meeting for this project, which had broad international collaboration from basic and clinical researchers and patient advocates.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0d3834d0c8df8d1fee6a93a60553d8e6Test
https://doi.org/10.1002/ajmg.a.61485Test

المؤلفون: Christopher L. Moertel, Margaret Semrud-Clikeman, Elizabeth I. Pierpont, Alana M. McNeill, Katherine Sommer, Allison M. H. Foy, Rebekah L. Hudock, Mary Ella M Pierpont, Ryan Shanley, Susan A. Berry

المصدر: American Journal of Medical Genetics Part A. 179:2433-2446

مصطلحات موضوعية: Male, Parents, 0301 basic medicine, Neurofibromatosis 1, Adolescent, Emotions, Psychological intervention, Child Behavior, Emotional functioning, 030105 genetics & heredity, 03 medical and health sciences, Rating scale, Surveys and Questionnaires, Genetics, Humans, Medicine, Attention deficit hyperactivity disorder, Genetic Predisposition to Disease, Neurofibromatosis, Child, Genetic Association Studies, Genetics (clinical), Depression (differential diagnoses), business.industry, Siblings, Noonan Syndrome, Age Factors, medicine.disease, Phenotype, 030104 developmental biology, Anxiety, Noonan syndrome, Female, Self Report, medicine.symptom, business, Clinical psychology

الوصف: While neurofibromatosis type 1 (NF1) and Noonan syndrome (NS) are clinically distinct genetic syndromes, they have overlapping features because they are caused by pathogenic variants in genes encoding molecules within the Ras-mitogen-activated protein kinase signaling pathway. Increased risk for emotional and behavioral challenges has been reported in both children and adults with these syndromes. The current study examined parent-report and self-report measures of emotional functioning among children with NF1 and NS as compared to their unaffected siblings. Parents and children with NS (n = 39), NF1 (n = 39), and their siblings without a genetic condition (n = 32) completed well-validated clinical symptom rating scales. Results from parent questionnaires indicated greater symptomatology on scales measuring internalizing behaviors and symptoms of attention deficit hyperactivity disorder (ADHD) in both syndrome groups as compared with unaffected children. Frequency and severity of emotional and behavioral symptoms were remarkably similar across the two clinical groups. Symptoms of depression and anxiety were higher in children who were also rated as meeting symptom criteria for ADHD. While self-report ratings by children generally correlated with parent ratings, symptom severity was less pronounced. Among unaffected siblings, parent ratings indicated higher than expected levels of anxiety. Study findings may assist with guiding family-based interventions to address emotional challenges.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c7501b6c7bb53898efb456936f97b5acTest
https://doi.org/10.1002/ajmg.a.61361Test

المؤلفون: Karl Degenhardt, Mark P. Johnson, Rebecca C. Ahrens-Nicklas, Stefanie Kasperski, Matthew J. O'Connor, Alyssa Ritter, Sanmati Cuddapah

المصدر: American Journal of Medical Genetics Part A. 179:1042-1046

مصطلحات موضوعية: Male, congenital, hereditary, and neonatal diseases and abnormalities, Pathology, medicine.medical_specialty, Neurofibromatosis 1, Genotype, Heart disease, Cardiomyopathy, Left ventricular hypertrophy, Ultrasonography, Prenatal, Fetus, Pregnancy, Intensive Care Units, Neonatal, Prenatal Diagnosis, Genetics, Humans, Medicine, Neurofibromatosis, Family history, neoplasms, Genetics (clinical), Neurofibromatosis type I, Neurofibromin 1, business.industry, Pregnancy Outcome, Genetic disorder, medicine.disease, eye diseases, nervous system diseases, Radiography, Phenotype, Mutation, Female, Hypertrophy, Left Ventricular, Differential diagnosis, Cardiomyopathies, business

الوصف: Neurofibromatosis type I (NF1) is a relatively common genetic disorder characterized by neurocutaneous lesions, neurofibromas, skeletal anomalies, iris hamartomas, and predisposition to other tumors. NF1 results from heterozygous loss-of-function mutations in neurofibromin (NF1), and diagnosis is most often made using clinical diagnostic criteria. Cardiac manifestations of NF1 include congenital heart disease (such as valvar pulmonary stenosis), left ventricular hypertrophy, and adult-onset pulmonary hypertension. Prenatal features of NF1 are often nonspecific and diagnoses are infrequently made prenatally without a known family history. Herein, we report the first case, to the best of our knowledge, of fetal cardiomyopathy as the presenting feature in NF1 and review NF1-related left ventricular hypertrophy. NF1 should be considered in the differential diagnosis for fetuses with cardiomyopathy, even in the absence of a known family history of the condition.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c29e41bbb02a8f7301ff6fd8bab8ef61Test
https://doi.org/10.1002/ajmg.a.61123Test

المؤلفون: Eva H. Baker, Katherine E. Warren, An N Dang Do, Simona Bianconi, Forbes D. Porter

المصدر: American Journal of Medical Genetics Part A. 176:386-390

مصطلحات موضوعية: Central Nervous System, Male, 0301 basic medicine, congenital, hereditary, and neonatal diseases and abnormalities, Pathology, medicine.medical_specialty, Neurofibromatosis 1, Adolescent, Central nervous system, Brain tumor, Article, Basal Ganglia, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Seizures, Basal ganglia, Genetics, medicine, Humans, Neurofibromatosis, Child, Genetics (clinical), Monomeric GTP-Binding Proteins, Neurons, Brain Neoplasms, business.industry, Metabolic disorder, Brain, nutritional and metabolic diseases, medicine.disease, Magnetic Resonance Imaging, Smith-Lemli-Opitz Syndrome, Cholesterol, 030104 developmental biology, medicine.anatomical_structure, Smith–Lemli–Opitz syndrome, Child, Preschool, Brain lesions, Brainstem, business, 030217 neurology & neurosurgery, Brain Stem

الوصف: Smith-Lemli-Opitz syndrome (SLOS) is a metabolic disorder caused by an inborn error of cholesterol synthesis that affects the development of many organ systems. Malformations in the central nervous system typically involve midline structures and reflect abnormal growth and differentiation of neurons and supporting cells. Despite these defects in central nervous system development, brain tumor formation has only rarely been reported in association with SLOS. We present three individuals with SLOS and lesions in the basal ganglia or brainstem detected by MRI that were concerning for tumor formation. However, the individuals' clinical and neurological course remained stable, and the lesions regressed after several years. These lesions have similarities to spongiotic changes observed in individuals with neurofibromatosis type 1 (NF1). Notably, impaired activity of small GTPases is present in both SLOS and NF1, perhaps giving mechanistic insight into the formation of these lesions.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::bb72146c753a61007f61160e601e2788Test
https://doi.org/10.1002/ajmg.a.38563Test

المؤلفون: Roope A. Kallionpää, Minna Pöyhönen, Tero Vahlberg, Sirkku Peltonen, Jussi Leppävirta, Elina Uusitalo, Susanna Timonen, Juha Peltonen

المصدر: American Journal of Medical Genetics Part A. 173:2641-2648

مصطلحات موضوعية: Adult, Male, 0301 basic medicine, congenital, hereditary, and neonatal diseases and abnormalities, medicine.medical_specialty, Neurofibromatosis 1, Preeclampsia, 03 medical and health sciences, 0302 clinical medicine, Pregnancy, Health care, Genetics, medicine, Humans, Registries, Neurofibromatosis, Child, neoplasms, Finland, Genetics (clinical), Retrospective Studies, Fetus, Cesarean Section, Obstetrics, business.industry, Incidence, Medical record, Odds ratio, ta3121, medicine.disease, eye diseases, nervous system diseases, 3. Good health, Pregnancy Complications, 030104 developmental biology, Cohort, Female, business, 030217 neurology & neurosurgery

الوصف: The objective of this retrospective total population study was to form a view of the pregnancies of the patients with neurofibromatosis type 1 (NF1). A cohort of 1,410 Finnish patients with NF1 was acquired by searching NF1-related inpatient and outpatient hospital visits and confirming the diagnoses by reviewing the medical records. Ten matched control persons per patient with NF1 were collected from Population Register Centre. Study persons were linked to data from Medical Birth Register and Care Register for Health Care through the personal identity code. Cesarean deliveries, hypertension/preeclampsia, and placental abruptions were more common among mothers with NF1 with adjusted odds ratios of 2.24 (95%CI 1.63-3.07), 1.96 (95%CI 1.18-3.24), and 13.40 (95%CI 4.26-42.13), respectively. The adjusted mean pregnancy duration was 0.65 (95%CI 0.42-0.88) weeks shorter among the mothers with NF1 than in the control group consisting of non-NF1 mothers giving birth to a non-NF1 child. The pregnancies of non-NF1 mothers giving birth to a NF1 child were 0.43 (95%CI 0.24-0.62) weeks shorter than in the control group. In summary, NF1 of the mother was associated with a shortened pregnancy and increased pregnancy complications. Also, the NF1 of the fetus slightly shortened pregnancy. Since mothers with NF1 are at increased risk for pregnancy complications, careful evaluation of their pregnancies is warranted.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c07efb3939e6a46056b30270761bc506Test
https://doi.org/10.1002/ajmg.a.38372Test

المؤلفون: Joel Charrow, Zabin S. Patel, Robert Listernick, Sally E. Jensen, Jin Shei Lai

المصدر: American Journal of Medical Genetics Part A. 173:79-87

مصطلحات موضوعية: Adult, Male, Neurofibromatosis 1, Adolescent, Physical function, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Physical functioning, Surveys and Questionnaires, Genetics, Humans, Medicine, Neurofibromatosis, Child, Qualitative Research, Genetics (clinical), Aged, Neurofibroma, Plexiform, business.industry, Patient-centered outcomes, Middle Aged, Disfigurement, medicine.disease, Patient Outcome Assessment, Phenotype, Socioeconomic Factors, Conceptual framework, Child, Preschool, 030220 oncology & carcinogenesis, Quality of Life, Anxiety, Female, Self Report, medicine.symptom, business, 030217 neurology & neurosurgery, Qualitative research, Clinical psychology

الوصف: Neurofibromatosis Type 1 (NF1) plexiform neurofibromas (pNFs) are associated with a variety of symptoms and concerns that affect patients' quality of life (QOL), highlighting the value of incorporating the patients' perspective when evaluating treatment outcomes. To better conceptualize the experience of patients with pNFs, this qualitative study sought to identify the most important outcomes to assess from the perspective of patients, families, and clinicians. Clinicians, patients age 5 years old and above, and parents of patients aged 5-17 years participated in semi-structured interviews to elicit the pNF symptoms/concerns considered most important to assess. The data were analyzed using an iterative coding procedure and the frequency with which symptoms/concerns emerged was tabulated. Eight clinicians, 31 patients, and 17 parents of patients participated in semi-structured interviews. The most frequently reported concerns raised by patients across all age groups included pain, appearance/disfigurement, social activity/role participation, stigma, and anxiety. For parents, physical functioning was the primary concern, followed by pain, social activity/role participation, appearance/disfigurement, and social relationships. The resulting conceptual framework included five domains to represent the most important identified symptoms/concerns: pain, social functioning, physical function impact, stigma, and emotional distress. This conceptual framework describing the symptoms/concerns of patients with pNF can help investigators create a measurement system to improve assessment of aspects of QOL only patients can report on. It may also provide the ability to identify symptoms/concerns that might warrant referrals to various clinical disciplines. © 2016 Wiley Periodicals, Inc.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::74d0fdb7bc36d5a410ae5e51de232989Test
https://doi.org/10.1002/ajmg.a.37987Test

المؤلفون: Roy E. Strowd, Jaishri O. Blakeley, James J. Vredenburgh, Alessandro Olivi, Fausto J. Rodriguez, Edward S. Ahn, Roger E. McLendon, Aaron B. Chance, George I. Jallo

المصدر: American Journal of Medical Genetics Part A. 170:1455-1461

مصطلحات موضوعية: Adult, Diagnostic Imaging, Male, Pediatrics, medicine.medical_specialty, Neurofibromatosis 1, Biopsy, Brain tumor, Astrocytoma, Article, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Genetics, medicine, Humans, Young adult, Neurofibromatosis, Genetics (clinical), Retrospective Studies, Pilocytic astrocytoma, business.industry, Case-control study, Brain, Retrospective cohort study, medicine.disease, Combined Modality Therapy, Phenotype, Treatment Outcome, Case-Control Studies, 030220 oncology & carcinogenesis, Cohort, Disease Progression, Female, Neoplasm Grading, business, 030217 neurology & neurosurgery

الوصف: Although optic pathway gliomas are the most common brain tumors associated with neurofibromatosis type 1 (NF1), extra-optic gliomas occur and may behave more aggressively with outcomes that differ by age. A retrospective case-control study was designed to describe the clinical course of adult NF1 patients with progressive extra-optic pilocytic astrocytomas (PAs) and compare to a pediatric cohort. Data for patients treated at the Johns Hopkins Comprehensive Neurofibromatosis Center from 2003 to 2013 were reviewed to identify cases (adults, age >18) and controls (pediatric, age

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2d1f8f9f8289da97038da94ea264b437Test
https://doi.org/10.1002/ajmg.a.37622Test

المؤلفون: Pamela L. Wolters, Katherine M. Burns, Andrea Gillespie, Mary Anne Toledo-Tamula, Andrea Baldwin, William N. Dudley, Staci Martin, Eva Dombi, Brigitte C. Widemann

المصدر: Am J Med Genet A

مصطلحات موضوعية: Male, Biopsychosocial model, Neurofibromatosis 1, Adolescent, Emotions, Population, Pain, Disease, Severity of Illness Index, Article, Quality of life, Surveys and Questionnaires, Adaptation, Psychological, Genetics, medicine, Humans, Child, education, Genetics (clinical), Neurofibroma, Plexiform, Social stress, education.field_of_study, business.industry, Mental Disorders, Chronic pain, medicine.disease, Caregivers, Quality of Life, Anxiety, Female, Pain catastrophizing, medicine.symptom, business, Clinical psychology

الوصف: The physical manifestations of neurofibromatosis type 1 (NF1) can cause chronic pain. This study investigated the impact of pain in youth with NF1 and plexiform neurofibromas (PNs) and its relationship to disease factors, social-emotional functioning, and quality of life (QOL) within a biopsychosocial framework. Caregivers of 59 children and adolescents with NF1 and PNs (6-18 years), and 41 of these youth (10-18 years), completed questionnaires assessing social-emotional functioning and QOL, including an item on pain interference. Measures of disease severity included total PN volume by percent body weight and number of disease complications. Both caregiver (73%) and self-report (59%) ratings indicated that pain interferes with the child's daily functioning despite 33% taking pain medication. Based on caregivers' behavior ratings, more symptoms of anxiety and larger tumor volumes predicted greater pain interference, while greater pain interference, worse depressive symptoms, and more disease complications predicted poorer QOL. As rated by adolescents, more symptoms of anxiety predicted greater pain interference, while greater pain interference and social stress predicted poorer QOL. Further, social-emotional problems mediate the relationship between pain interference and QOL. Thus, pain interferes with daily functioning in the majority of youth with NF1 and PNs even when using pain medication. The impact of pain interference, disease severity, and particularly social-emotional problems on QOL highlights the interaction between physical and psychological states in NF1. Future research and treatment of pain in this population should utilize a biopsychosocial approach and involve multidisciplinary therapies including psychological interventions that target social-emotional functioning.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::dc104a8d77243c6071b79565d35dc3fbTest
https://doi.org/10.1002/ajmg.a.37123Test

المؤلفون: Piranit Nik Kantaputra, Tumtip Sangruchi, Chanin Limwongse, Ans M.W. van den Ouweland

المساهمون: Clinical Genetics

المصدر: American Journal of Medical Genetics Part A, 158A(7), 1750-1753. Wiley-Liss Inc.

مصطلحات موضوعية: medicine.medical_specialty, congenital, hereditary, and neonatal diseases and abnormalities, Neurofibromatosis 1, Plexiform neurofibroma, Genes, Neurofibromatosis 1, Genetics, Medicine, Humans, Eye Abnormalities, Neurofibromatosis, NF1 Mutation, Genetics (clinical), Aged, Neurofibroma, Plexiform, biology, Blindness, Base Sequence, business.industry, Exons, Middle Aged, medicine.disease, Neurofibromin 1, Dermatology, Magnetic Resonance Imaging, Face, Mutation, biology.protein, Tears, Female, sense organs, business, Novel mutation

الوصف: A Thai woman, who was affected with neurofibromatosis type 1, was followed up and re-evaluated at ages 45, 61, and 67 years. Her mother and her three brothers were also affected. The proposita was very severely affected. She was born blind with underdeveloped eyeglobes and had large plexiform neurofibromas on her face. Her eyelids were gigantic and tears drained from the orifice between them. Cutaneous neurofibromas were observed all over her body. A novel mutation c.4821delA was identified in NF1 gene, which predicted truncation of neurofibromin (p.Leu1607fs). (C) 2012 Wiley Periodicals, Inc.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::da9a1b7d2fd47b5b4da948d3cd020b1cTest
https://hdl.handle.net/1765/74074Test