The Experts below are selected from a list of 306 Experts worldwide ranked by ideXlab platform
Katherine A Rauen - One of the best experts on this subject based on the ideXlab platform.
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fetal autopsy findings of Cardiofaciocutaneous Syndrome with a unique braf mutation
Pediatric and Developmental Pathology, 2014Co-Authors: Jefferson Terry, Katherine A Rauen, Malgorzata J M NowaczykAbstract:Cardiofaciocutaneous (CFC) Syndrome is a RASopathy phenotypically characterized by facial, cardiac, and ectodermal abnormalities. The extent to which this phenotype is expressed in the affected fetus is unclear, and a better understanding of the fetal autopsy findings in CFC Syndrome could facilitate diagnosis and understanding of the developmental effects of dysregulated BRAF activity. Here we describe the fetal autopsy findings in a case of CFC Syndrome in a 17-week fetus with a novel BRAF mutation that demonstrates potential similarities and differences with the postnatal presentation of CFC Syndrome.
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dermatological findings in 61 mutation positive individuals with Cardiofaciocutaneous Syndrome
British Journal of Dermatology, 2011Co-Authors: Dawn H Siegel, J Mckenzie, Ilona J Frieden, Katherine A RauenAbstract:Background The RASopathies are a class of human genetic Syndromes that are caused by germline mutations in genes which encode components of the Ras/MAPK pathway. Cardio-facio-cutaneous (CFC) Syndrome is characterized by distinctive craniofacial features, congenital heart defects, and abnormalities of the skin and hair.
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effects of germline mutations in the ras mapk signaling pathway on adaptive behavior Cardiofaciocutaneous Syndrome and noonan Syndrome
American Journal of Medical Genetics Part A, 2010Co-Authors: Elizabeth I Pierpont, Amy E. Roberts, Mary Ella M Pierpont, Nancy J Mendelsohn, Erica Tworogdube, Katherine A Rauen, Mark S SeidenbergAbstract:Cardiofaciocutaneous Syndrome (CFC) and Noonan Syndrome (NS) are two phenotypically overlapping genetic disorders whose underlying molecular etiologies affect a common signaling pathway. Mutations in the BRAF, MEK1, and MEK2 genes cause most cases of CFC and mutations in PTPN11, SOS1, KRAS, and RAF1 typically cause NS. Although both Syndromes are associated with developmental delays of varying severity, the extent to which the behavioral profiles differ may shed light on the different roles these respective genes play in development of skills necessary for everyday functioning. In this study, profiles of adaptive behavior of individuals with CFC and NS who had confirmed pathogenic mutations in Ras/mitogen-activated protein kinase (MAPK) pathway genes were investigated. Patterns of strengths and weaknesses, age-related differences, and risk factors for difficulties in adaptive skills were assessed. Although genes acting more downstream in the Ras/MAPK pathway were associated with more difficulties in adaptive functioning than genes more upstream in the pathway, several inconsistencies highlight the wide spectrum of possible developmental courses in CFC and NS. Along with clinical and genetic factors, variables such as chronological age, gestational age at birth, and parental education levels accounted for significant variance in adaptive skills. Results indicate that there is wide heterogeneity in adaptive functioning in CFC and NS, but that these abilities are correlated to some extent with the specific disease-causing genes.
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effects of germline mutations in the ras mapk signaling pathway on adaptive behavior Cardiofaciocutaneous Syndrome and
2010Co-Authors: Elizabeth I Pierpont, Amy E. Roberts, Mary Ella M Pierpont, Nancy J Mendelsohn, Erica Tworogdube, Katherine A Rauen, Mark S SeidenbergAbstract:Cardiofaciocutaneous Syndrome (CFC) and Noonan Syndrome(NS)aretwophenotypicallyoverlappinggeneticdisorderswhoseunderlying molecular etiologies affect a common signaling path-way. Mutations in the BRAF, MEK1, and MEK2 genes cause mostcases of CFC and mutations in PTPN11, SOS1, KRAS, and RAF1typically cause NS. Although both Syndromes are associated withdevelopmental delays of varying severity, the extent to which thebehavioral profiles differ may shed light on the different rolesthese respective genes play in development of skills necessary foreveryday functioning. In this study, profiles of adaptive behaviorof individuals with CFC and NS who had confirmed pathogenicmutations in Ras/mitogen-activated protein kinase (MAPK)pathway genes were investigated. Patterns of strengths andweaknesses, age-related differences, and risk factors for difficul-ties in adaptive skills were assessed. Although genes acting moredownstream in the Ras/MAPK pathway were associated withmore difficulties in adaptive functioning than genes more up-stream in the pathway, several inconsistencies highlight the widespectrum of possible developmental courses in CFC and NS.Along with clinical and genetic factors, variables such as chro-nological age, gestational age at birth, and parental educationlevels accounted for significant variance in adaptive skills. Re-sults indicate that there is wide heterogeneity in adaptive func-tioning in CFC and NS, but that these abilities are correlated tosome extent with the specific disease-causing genes.
Elizabeth I Pierpont - One of the best experts on this subject based on the ideXlab platform.
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behavioral functioning in Cardiofaciocutaneous Syndrome risk factors and impact on parenting experience
American Journal of Medical Genetics Part A, 2016Co-Authors: Elizabeth I Pierpont, Melinda WolfordAbstract:The present study is an investigation of behavioral functioning in children with Cardiofaciocutaneous Syndrome (CFC). CFC is a rare single-gene disorder associated with cardiac disease, characteristic skin and facial features, intellectual disability, and neurological complications such as seizures and structural brain anomalies. Emotional and behavioral features of CFC have not been systematically investigated. We aimed to identify key variables that contribute to psychopathology during childhood and adolescence, and to examine the impact of challenging behaviors on the caregiving experience. Parents of 34 children and adolescents with CFC completed standardized broadband measures of child emotional and behavioral functioning, as well as measures of sensory modulation, functional communication, and caregiver stress. Results indicate that children with CFC Syndrome are at heightened risk for psychopathology, with attention problems, social difficulties, and unusual behaviors (e.g., obsessive thoughts, strange behaviors, repetitive acts) found to be especially prevalent. Behavioral challenges in children with CFC Syndrome were significantly associated with a history of obstetric complications and with problems modulating sensory information. With regard to the impact of child neurocognitive and behavioral issues on the caregiving experience, parent self-reported stress was significantly higher among parents of children who engaged in more problem behaviors, and lower among parents whose children could communicate effectively with others. Results of this study suggest avenues to help families cope with CFC-related stressors and enhance overall functioning. In particular, this study highlights the need for educational and treatment interventions aimed at addressing sensory needs, increasing functional communication, and identifying and managing challenging behaviors. © 2016 Wiley Periodicals, Inc.
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effects of germline mutations in the ras mapk signaling pathway on adaptive behavior Cardiofaciocutaneous Syndrome and noonan Syndrome
American Journal of Medical Genetics Part A, 2010Co-Authors: Elizabeth I Pierpont, Amy E. Roberts, Mary Ella M Pierpont, Nancy J Mendelsohn, Erica Tworogdube, Katherine A Rauen, Mark S SeidenbergAbstract:Cardiofaciocutaneous Syndrome (CFC) and Noonan Syndrome (NS) are two phenotypically overlapping genetic disorders whose underlying molecular etiologies affect a common signaling pathway. Mutations in the BRAF, MEK1, and MEK2 genes cause most cases of CFC and mutations in PTPN11, SOS1, KRAS, and RAF1 typically cause NS. Although both Syndromes are associated with developmental delays of varying severity, the extent to which the behavioral profiles differ may shed light on the different roles these respective genes play in development of skills necessary for everyday functioning. In this study, profiles of adaptive behavior of individuals with CFC and NS who had confirmed pathogenic mutations in Ras/mitogen-activated protein kinase (MAPK) pathway genes were investigated. Patterns of strengths and weaknesses, age-related differences, and risk factors for difficulties in adaptive skills were assessed. Although genes acting more downstream in the Ras/MAPK pathway were associated with more difficulties in adaptive functioning than genes more upstream in the pathway, several inconsistencies highlight the wide spectrum of possible developmental courses in CFC and NS. Along with clinical and genetic factors, variables such as chronological age, gestational age at birth, and parental education levels accounted for significant variance in adaptive skills. Results indicate that there is wide heterogeneity in adaptive functioning in CFC and NS, but that these abilities are correlated to some extent with the specific disease-causing genes.
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effects of germline mutations in the ras mapk signaling pathway on adaptive behavior Cardiofaciocutaneous Syndrome and
2010Co-Authors: Elizabeth I Pierpont, Amy E. Roberts, Mary Ella M Pierpont, Nancy J Mendelsohn, Erica Tworogdube, Katherine A Rauen, Mark S SeidenbergAbstract:Cardiofaciocutaneous Syndrome (CFC) and Noonan Syndrome(NS)aretwophenotypicallyoverlappinggeneticdisorderswhoseunderlying molecular etiologies affect a common signaling path-way. Mutations in the BRAF, MEK1, and MEK2 genes cause mostcases of CFC and mutations in PTPN11, SOS1, KRAS, and RAF1typically cause NS. Although both Syndromes are associated withdevelopmental delays of varying severity, the extent to which thebehavioral profiles differ may shed light on the different rolesthese respective genes play in development of skills necessary foreveryday functioning. In this study, profiles of adaptive behaviorof individuals with CFC and NS who had confirmed pathogenicmutations in Ras/mitogen-activated protein kinase (MAPK)pathway genes were investigated. Patterns of strengths andweaknesses, age-related differences, and risk factors for difficul-ties in adaptive skills were assessed. Although genes acting moredownstream in the Ras/MAPK pathway were associated withmore difficulties in adaptive functioning than genes more up-stream in the pathway, several inconsistencies highlight the widespectrum of possible developmental courses in CFC and NS.Along with clinical and genetic factors, variables such as chro-nological age, gestational age at birth, and parental educationlevels accounted for significant variance in adaptive skills. Re-sults indicate that there is wide heterogeneity in adaptive func-tioning in CFC and NS, but that these abilities are correlated tosome extent with the specific disease-causing genes.
Amy E. Roberts - One of the best experts on this subject based on the ideXlab platform.
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Cardiomyopathies in Noonan Syndrome and the other RASopathies
Progress in pediatric cardiology, 2015Co-Authors: Bruce D. Gelb, Amy E. Roberts, Marco TartagliaAbstract:Noonan Syndrome and related disorders (Noonan Syndrome with multiple lentigines, Costello Syndrome, Cardiofaciocutaneous Syndrome, Noonan Syndrome with loose anagen hair, and other related traits) are autosomal dominant traits. Mutations causing these disorders alter proteins relevant for signaling through RAS. Thus, these traits are now collectively called the RASopathies. While the RASopathies have pleiomorphic features, this review will focus on the hypertrophic cardiomyopathy observed in varying percentages of all of these traits. In addition, inherited abnormalities in one pathway gene, RAF1, cause pediatric-onset dilated cardiomyopathy. The pathogeneses for the RASopathy-associated cardiomyopathies are being elucidated, principally using animal models, leading to genotype-specific insights into how signal transduction is perturbed. Based on those findings, small molecule therapies seem possible for RASopathy-associated cardiomyopathies.
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effects of germline mutations in the ras mapk signaling pathway on adaptive behavior Cardiofaciocutaneous Syndrome and noonan Syndrome
American Journal of Medical Genetics Part A, 2010Co-Authors: Elizabeth I Pierpont, Amy E. Roberts, Mary Ella M Pierpont, Nancy J Mendelsohn, Erica Tworogdube, Katherine A Rauen, Mark S SeidenbergAbstract:Cardiofaciocutaneous Syndrome (CFC) and Noonan Syndrome (NS) are two phenotypically overlapping genetic disorders whose underlying molecular etiologies affect a common signaling pathway. Mutations in the BRAF, MEK1, and MEK2 genes cause most cases of CFC and mutations in PTPN11, SOS1, KRAS, and RAF1 typically cause NS. Although both Syndromes are associated with developmental delays of varying severity, the extent to which the behavioral profiles differ may shed light on the different roles these respective genes play in development of skills necessary for everyday functioning. In this study, profiles of adaptive behavior of individuals with CFC and NS who had confirmed pathogenic mutations in Ras/mitogen-activated protein kinase (MAPK) pathway genes were investigated. Patterns of strengths and weaknesses, age-related differences, and risk factors for difficulties in adaptive skills were assessed. Although genes acting more downstream in the Ras/MAPK pathway were associated with more difficulties in adaptive functioning than genes more upstream in the pathway, several inconsistencies highlight the wide spectrum of possible developmental courses in CFC and NS. Along with clinical and genetic factors, variables such as chronological age, gestational age at birth, and parental education levels accounted for significant variance in adaptive skills. Results indicate that there is wide heterogeneity in adaptive functioning in CFC and NS, but that these abilities are correlated to some extent with the specific disease-causing genes.
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effects of germline mutations in the ras mapk signaling pathway on adaptive behavior Cardiofaciocutaneous Syndrome and
2010Co-Authors: Elizabeth I Pierpont, Amy E. Roberts, Mary Ella M Pierpont, Nancy J Mendelsohn, Erica Tworogdube, Katherine A Rauen, Mark S SeidenbergAbstract:Cardiofaciocutaneous Syndrome (CFC) and Noonan Syndrome(NS)aretwophenotypicallyoverlappinggeneticdisorderswhoseunderlying molecular etiologies affect a common signaling path-way. Mutations in the BRAF, MEK1, and MEK2 genes cause mostcases of CFC and mutations in PTPN11, SOS1, KRAS, and RAF1typically cause NS. Although both Syndromes are associated withdevelopmental delays of varying severity, the extent to which thebehavioral profiles differ may shed light on the different rolesthese respective genes play in development of skills necessary foreveryday functioning. In this study, profiles of adaptive behaviorof individuals with CFC and NS who had confirmed pathogenicmutations in Ras/mitogen-activated protein kinase (MAPK)pathway genes were investigated. Patterns of strengths andweaknesses, age-related differences, and risk factors for difficul-ties in adaptive skills were assessed. Although genes acting moredownstream in the Ras/MAPK pathway were associated withmore difficulties in adaptive functioning than genes more up-stream in the pathway, several inconsistencies highlight the widespectrum of possible developmental courses in CFC and NS.Along with clinical and genetic factors, variables such as chro-nological age, gestational age at birth, and parental educationlevels accounted for significant variance in adaptive skills. Re-sults indicate that there is wide heterogeneity in adaptive func-tioning in CFC and NS, but that these abilities are correlated tosome extent with the specific disease-causing genes.
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the Cardiofaciocutaneous Syndrome
Journal of Medical Genetics, 2006Co-Authors: Amy E. Roberts, Maria Ines Kavamura, Judith E Allanson, Suzanne K Jadico, Jacqueline A Noonan, John M Opitz, Terri L Young, Giovanni NeriAbstract:The Cardiofaciocutaneous (CFC) Syndrome is a condition of sporadic occurrence, with patients showing multiple congenital anomalies and mental retardation. It is characterised by failure to thrive, relative macrocephaly, a distinctive face with prominent forehead, bitemporal constriction, absence of eyebrows, hypertelorism, downward‐slanting palpebral fissures often with epicanthic folds, depressed nasal root and a bulbous tip of the nose. The cutaneous involvement consists of dry, hyperkeratotic, scaly skin, sparse and curly hair, and cavernous haemangiomata. Most patients have a congenital heart defect, most commonly pulmonic stenosis and hypertrophic cardiomyopathy. The developmental delay usually is moderate to severe. The Syndrome is caused by gain‐of‐function mutations in four different genes BRAF, KRAS, mitogen‐activated protein/extracellular signal‐regulated kinase MEK1 and MEK2, all belonging to the same RAS–extracellular signal‐regulated kinase (ERK) pathway that regulates cell differentiation, proliferation and apoptosis. The CFC Syndrome is a member of a family of Syndromes that includes the Noonan and Costello Syndromes, presenting with phenotypic similarities. Noonan Syndrome is caused by mutations in the protein tyrosine phosphatase SHP‐2 gene (PTPN11), with a few people having a mutation in KRAS. Costello Syndrome is caused by mutations in HRAS. The protein products of these genes also belong to the RAS–ERK pathway. Thus, the clinical overlap of these three conditions, which often poses a problem of differential diagnosis, is explained by their pathogenetic relatedness.
Mark S Seidenberg - One of the best experts on this subject based on the ideXlab platform.
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effects of germline mutations in the ras mapk signaling pathway on adaptive behavior Cardiofaciocutaneous Syndrome and noonan Syndrome
American Journal of Medical Genetics Part A, 2010Co-Authors: Elizabeth I Pierpont, Amy E. Roberts, Mary Ella M Pierpont, Nancy J Mendelsohn, Erica Tworogdube, Katherine A Rauen, Mark S SeidenbergAbstract:Cardiofaciocutaneous Syndrome (CFC) and Noonan Syndrome (NS) are two phenotypically overlapping genetic disorders whose underlying molecular etiologies affect a common signaling pathway. Mutations in the BRAF, MEK1, and MEK2 genes cause most cases of CFC and mutations in PTPN11, SOS1, KRAS, and RAF1 typically cause NS. Although both Syndromes are associated with developmental delays of varying severity, the extent to which the behavioral profiles differ may shed light on the different roles these respective genes play in development of skills necessary for everyday functioning. In this study, profiles of adaptive behavior of individuals with CFC and NS who had confirmed pathogenic mutations in Ras/mitogen-activated protein kinase (MAPK) pathway genes were investigated. Patterns of strengths and weaknesses, age-related differences, and risk factors for difficulties in adaptive skills were assessed. Although genes acting more downstream in the Ras/MAPK pathway were associated with more difficulties in adaptive functioning than genes more upstream in the pathway, several inconsistencies highlight the wide spectrum of possible developmental courses in CFC and NS. Along with clinical and genetic factors, variables such as chronological age, gestational age at birth, and parental education levels accounted for significant variance in adaptive skills. Results indicate that there is wide heterogeneity in adaptive functioning in CFC and NS, but that these abilities are correlated to some extent with the specific disease-causing genes.
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effects of germline mutations in the ras mapk signaling pathway on adaptive behavior Cardiofaciocutaneous Syndrome and
2010Co-Authors: Elizabeth I Pierpont, Amy E. Roberts, Mary Ella M Pierpont, Nancy J Mendelsohn, Erica Tworogdube, Katherine A Rauen, Mark S SeidenbergAbstract:Cardiofaciocutaneous Syndrome (CFC) and Noonan Syndrome(NS)aretwophenotypicallyoverlappinggeneticdisorderswhoseunderlying molecular etiologies affect a common signaling path-way. Mutations in the BRAF, MEK1, and MEK2 genes cause mostcases of CFC and mutations in PTPN11, SOS1, KRAS, and RAF1typically cause NS. Although both Syndromes are associated withdevelopmental delays of varying severity, the extent to which thebehavioral profiles differ may shed light on the different rolesthese respective genes play in development of skills necessary foreveryday functioning. In this study, profiles of adaptive behaviorof individuals with CFC and NS who had confirmed pathogenicmutations in Ras/mitogen-activated protein kinase (MAPK)pathway genes were investigated. Patterns of strengths andweaknesses, age-related differences, and risk factors for difficul-ties in adaptive skills were assessed. Although genes acting moredownstream in the Ras/MAPK pathway were associated withmore difficulties in adaptive functioning than genes more up-stream in the pathway, several inconsistencies highlight the widespectrum of possible developmental courses in CFC and NS.Along with clinical and genetic factors, variables such as chro-nological age, gestational age at birth, and parental educationlevels accounted for significant variance in adaptive skills. Re-sults indicate that there is wide heterogeneity in adaptive func-tioning in CFC and NS, but that these abilities are correlated tosome extent with the specific disease-causing genes.
Nancy J Mendelsohn - One of the best experts on this subject based on the ideXlab platform.
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effects of germline mutations in the ras mapk signaling pathway on adaptive behavior Cardiofaciocutaneous Syndrome and noonan Syndrome
American Journal of Medical Genetics Part A, 2010Co-Authors: Elizabeth I Pierpont, Amy E. Roberts, Mary Ella M Pierpont, Nancy J Mendelsohn, Erica Tworogdube, Katherine A Rauen, Mark S SeidenbergAbstract:Cardiofaciocutaneous Syndrome (CFC) and Noonan Syndrome (NS) are two phenotypically overlapping genetic disorders whose underlying molecular etiologies affect a common signaling pathway. Mutations in the BRAF, MEK1, and MEK2 genes cause most cases of CFC and mutations in PTPN11, SOS1, KRAS, and RAF1 typically cause NS. Although both Syndromes are associated with developmental delays of varying severity, the extent to which the behavioral profiles differ may shed light on the different roles these respective genes play in development of skills necessary for everyday functioning. In this study, profiles of adaptive behavior of individuals with CFC and NS who had confirmed pathogenic mutations in Ras/mitogen-activated protein kinase (MAPK) pathway genes were investigated. Patterns of strengths and weaknesses, age-related differences, and risk factors for difficulties in adaptive skills were assessed. Although genes acting more downstream in the Ras/MAPK pathway were associated with more difficulties in adaptive functioning than genes more upstream in the pathway, several inconsistencies highlight the wide spectrum of possible developmental courses in CFC and NS. Along with clinical and genetic factors, variables such as chronological age, gestational age at birth, and parental education levels accounted for significant variance in adaptive skills. Results indicate that there is wide heterogeneity in adaptive functioning in CFC and NS, but that these abilities are correlated to some extent with the specific disease-causing genes.
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effects of germline mutations in the ras mapk signaling pathway on adaptive behavior Cardiofaciocutaneous Syndrome and
2010Co-Authors: Elizabeth I Pierpont, Amy E. Roberts, Mary Ella M Pierpont, Nancy J Mendelsohn, Erica Tworogdube, Katherine A Rauen, Mark S SeidenbergAbstract:Cardiofaciocutaneous Syndrome (CFC) and Noonan Syndrome(NS)aretwophenotypicallyoverlappinggeneticdisorderswhoseunderlying molecular etiologies affect a common signaling path-way. Mutations in the BRAF, MEK1, and MEK2 genes cause mostcases of CFC and mutations in PTPN11, SOS1, KRAS, and RAF1typically cause NS. Although both Syndromes are associated withdevelopmental delays of varying severity, the extent to which thebehavioral profiles differ may shed light on the different rolesthese respective genes play in development of skills necessary foreveryday functioning. In this study, profiles of adaptive behaviorof individuals with CFC and NS who had confirmed pathogenicmutations in Ras/mitogen-activated protein kinase (MAPK)pathway genes were investigated. Patterns of strengths andweaknesses, age-related differences, and risk factors for difficul-ties in adaptive skills were assessed. Although genes acting moredownstream in the Ras/MAPK pathway were associated withmore difficulties in adaptive functioning than genes more up-stream in the pathway, several inconsistencies highlight the widespectrum of possible developmental courses in CFC and NS.Along with clinical and genetic factors, variables such as chro-nological age, gestational age at birth, and parental educationlevels accounted for significant variance in adaptive skills. Re-sults indicate that there is wide heterogeneity in adaptive func-tioning in CFC and NS, but that these abilities are correlated tosome extent with the specific disease-causing genes.