China
Africa
Explore chapters and articles related to this topic
Cardiac Disease
Published in Praveen S. Goday, Cassandra L. S. Walia, Pediatric Nutrition for Dietitians, 2022
Megan Horsley, Jeffrey Anderson
One complication or disorder that occurs in patients with CHD is chylothorax. Chylothorax is associated with increased mortality, hospital length of stay, intensive care unit length of stay, time on mechanical ventilation, extracorporeal membrane oxygenation use, and cost. This occurs when there is the presence of lymphatic fluid (chyle) in the pleural space caused by damage to the thoracic duct or lympho-venous connections or secondary to lymphatic abnormalities. It is often a result of iatrogenic complications of cardiothoracic surgery, commonly caused by trauma to the thoracic duct or other surrounding lymphatic tributaries. It has also been described in children with genetic syndromes associated with CHD, including trisomy 21, Noonan’s syndrome, Turner’s syndrome, and cardio-facio-cutaneous syndrome. Additionally, chylothorax can result from high central venous pressure within the superior vena cava (SVC), thereby affecting the pressure in the lymphatic system and inability of the lymphatic system to adequately drain into the bloodstream. This is seen mainly in operations that cause increased SVC pressure, such as the hemi-Fontan or bidirectional Glenn, Fontan, and Senning procedures, and can also be seen in patients with thrombus occluding the SVC or subclavian vessels.
Dysmorphology and genetic syndromes
Published in Angus Clarke, Alex Murray, Julian Sampson, Harper's Practical Genetic Counselling, 2019
In the past, clinicians had to rely almost entirely on their own skills and experience to make an accurate diagnosis. With the accumulation of experience in specific centres and by particular individuals, regular meetings of interested physicians refined this knowledge, and valuable books and databases were produced that helped to disseminate the knowledge and wisdom of this craft. The clinical delineation of dysmorphic syndromes interacted most productively with mammalian developmental biology and the study of mouse (and other animal) models of the disorders found in human patients. This interaction led to the recognition of the underlying genetic basis of many of these disorders and to the realisation that disorders with similar features often resulted from mutation in functionally related genes (genes involved in the same developmental or biochemical pathway or the same physiological process). The most clearly established pathway of this type is the Ras pathway of functionally interacting proteins involved in inter- and intra-cellular signalling. Mutations that affect these proteins lead to a number of related phenotypes, including Noonan syndrome, Costello syndrome, cardio-facio-cutaneous syndrome and neurofibromatosis type 1.
Personalized Medicine in Hereditary Cancer Syndromes
Published in II-Jin Kim, Cancer Genetics and Genomics for Personalized Medicine, 2017
The underlying genetic mutations affect different sections of the RAS/RAF/MAPK pathway in each syndrome. Noonan syndrome is associated with mutations in the PTPN11, KRAS, SOS, and RAF1 genes [44]. LEOPARD syndrome is associated with mutations in PTPN11 and RAF1. Patients with Costello syndrome have mutations in the HRAS gene. Patients with cardiofaciocutaneous syndrome have mutations in BRAF, MAP2K1 and MAP2K2, and KRAS [44].
Primary diffuse leptomeningeal glioneuronal tumors of the central nervous system: Report of three cases and review of literature
Published in Pediatric Hematology and Oncology, 2020
Chenue Abongwa, Jennifer Cotter, Benita Tamrazi, Girish Dhall, Tom Davidson, Ashley Margol
More recent reports of DLGNT have included molecular analyses highlighting the common finding of alterations in the MAPK pathway and 1p deletion.15,16 In one recent publication, a variety of genomic alterations in the MAPK pathway were identified in 6/10 patients.16 One of these patients had a germline RAF1 mutation and a clinical diagnosis of cardio-facio-cutaneous syndrome. BRAF duplications were identified in four of the patients and the BRAFV600E mutation identified in one patient.16 In another recent report, the BRAFV600E mutation was not identified in all the tumors tested in the series.17 We attempted to perform molecular testing but in all three cases the biopsy samples were small and yielded insufficient nucleic acid for analysis. Although FISH for 1p and 19q and other molecular studies could not be done in the patients in our series, their clinical presentation, pathological findings and clinical course contributes to the understanding of the presentation and natural history of this disease.
Pathogenic gene variants identified in patients with retinitis pigmentosa at the referral center clinic of the University of Minnesota (UMN)
Published in Ophthalmic Genetics, 2023
Richard Sather, Jacie Ihinger, Tahsin Khundkar, Sandra R. Montezuma
A total of 199 patients with RP met criteria for inclusion. The patient distribution consisted of 151 (75.9%) with non-syndromic RP and 48 (24.1%) with syndromic RP. The Syndromic RP patient numbers included Usher Syndrome (39), Bardet Biedl Syndrome (4), Cohen Syndrome (2), nephronophthisis (1), Cardiofaciocutaneous Syndrome (1), and abetaproteinemia (1).
Ophthalmic manifestations in Costello syndrome caused by Ras pathway dysregulation during development
Published in Ophthalmic Genetics, 2022
Suma P. Shankar, Reshmitha Fallurin, Tonya Watson, Prabhu R. Shankar, Terri L. Young, Deborah Orel-Bixler, Katherine A. Rauen
Costello syndrome (CS) (1,2) is a genetic disorder with a prevalence of 1:300,000 to 1:1.25 million (ORPHA: 3071) and belongs to a class of neurodevelopmental disorders referred to as the RASopathies (3,4). Dominant de-novo mutations in the HRAS gene encoding a product of the Ras signal transduction pathway causes Costello syndrome (OMIM: # 218040) (5,6). Dysregulation of other genes in the Ras pathway result in similar syndromes having significant phenotypic overlap and include neurofibromatosis 1 (NF1), cardiofaciocutaneous syndrome (CFC), Noonan syndrome (NS), Noonan syndrome with multiple lentigines (NSML), and Legius syndrome (7). Costello syndrome is a multisystem disorder characterized by distinctive cranio-facial features, including macrocephaly, congenital heart defects, such as pulmonic stenosis, cardiac rhythm disturbances and hypertrophic cardiomyopathy, neurological features including hydrocephalus, syringomyelia, postnatal cerebellar overgrowth and neurocognitive impairment, dermatologic findings such as nasal papilloma, hemangiomas, keratosis pilaris, palmoplantar keratoderma, and, musculoskeletal features such as ulnar deviation, short Achilles tendon, hip joint problems and myopathies. A predisposition to neoplasia development, both benign and malignant has also been described (8–11). Although ocular findings such as dolichocilia (long eyelashes), strabismus, nystagmus, refractive errors and visual disturbances have been described in CS (12), these were collated using retrospective medical record analysis. A comprehensive standardized in-person study of ophthalmic manifestations has never been performed and reported in these individuals (12). Activating mutations in HRAS, the only gene of the Ras pathway associated with CS, results in hyperactivation of Ras pathway, a highly conserved key regulator of fundamental cellular functions such as cell differentiation, migration and proliferation (3). The role of Ras pathway in eye development has been reported in a number of in vivo studies in Drosophila (13,14), xenopus (15) and mouse models (16) as well as in in vitro models (17). Further, ERK, a downstream effector of the Ras pathway is reported to be a key factor in the synaptic plasticity of the visual cortex (18,19). Ocular manifestations have been reported in other RASopathies including NF1, CFC and NS (20–22). We sought to evaluate the visual function and ocular features of CS in a comprehensive manner in this study.