Читать книгу Genetic Disorders and the Fetus - Группа авторов - Страница 2
Table of Contents
Оглавление1 Cover
5 Preface
8 1 Genetic Counseling: Preconception, Prenatal, and Perinatal The burden of genetic disorders and congenital malformations Incidence and prevalence of genetic disorders and congenital malformations Congenital malformations and infant morbidity and mortality The goal and purpose of prenatal diagnosis Prerequisites for genetic counseling Guiding principles for genetic counseling Preconception genetic counseling Genetic counseling as a prelude to prenatal diagnosis Perinatal genetic counseling The efficacy of genetic counseling References
9 2 Preimplantation Genetic Testing Approaches to preimplantation genetic testing Preimplantation genetic analysis Ethical and legal issues Conclusion References
10 3 Amniotic Fluid Constituents, Cell Culture, and Neural Tube Defects Introduction Amniotic fluid Amniotic fluid cell culture References
11 4 Molecular Aspects of Placental Development Overview Placental structure Placental development and function Placental insufficiency Fetal growth restriction Preeclampsia Genetic findings associated with molar changes in the placenta Placental mesenchymal dysplasia DNA methylation studies in the placenta and their clinical application Epigenetic studies in the placenta and environment The placenta as a predictor of child health Further considerations References
12 5 Fetal Origins of Adult Health and Disease Introduction Epigenetics and programming Energy‐balance programming: under‐ and overnutrition Environmental toxins Maternal stress and anxiety Glucocorticoids and prematurity Organ‐specific programming effects Conclusion References
13 6 Maternal Serum Screening for Chromosomal Abnormalities and Neural Tube Defects Chromosomal abnormalities Neural tube defects Screening and prenatal diagnosis Widely used markers Additional markers Marker distributions in Down syndrome, neural tube defect, and unaffected pregnancies Risk screening for Down syndrome Age‐specific Down syndrome risk at term Down syndrome risk at the time of the test Down syndrome likelihood ratios Modeling performance of Down syndrome screening Established multimarker Down syndrome policies Model performance of neural tube defect screening Prospective confirmation of the Down syndrome model Further multimarker Down syndrome strategies Ultrasound screening for OSB Other Down syndrome markers Clinical factors Edwards syndrome (trisomy 18) Other conditions associated with altered markers Planning a program Conclusion Acknowledgments References
14 7 Noninvasive Screening for Aneuploidy Using Cell‐Free Placental DNA Introduction Cell‐free DNA Performance of cell‐free DNA screening Sex chromosome aneuploidy Cell‐free DNA screening approaches Cell‐free DNA test failures False‐positive cell‐free DNA results and incidental findings False‐negative cell‐free DNA results Cell‐free DNA screening for microdeletion syndromes Genome‐wide cell‐free DNA screening Pretest counseling Post‐test screening Comparison of cell‐free DNA screening to traditional screening Use of prenatal ultrasound in the setting of cell‐free DNA Multiple gestations Cell‐based noninvasive prenatal testing Conclusion References
15 8 Noninvasive Prenatal Diagnosis and Screening for Monogenic Disorders Using Cell‐Free DNA Introduction Biology and characteristics of cell‐free DNA in maternal blood General approaches for testing of single‐gene disorders by fetal cell‐free DNA analysis Current status of noninvasive single‐gene testing by cell‐free DNA analysis Noninvasive prenatal diagnosis of monogenic disorders Noninvasive prenatal screening using panels of single‐gene disorders by cell‐free DNA analysis Clinical implementation: ethical and social issues Summary and future directions References
16 9 Amniocentesis, Chorionic Villus Sampling, and Fetal Blood Sampling Introduction Amniocentesis Chorionic villus sampling Fetal blood sampling Cardiocentesis References
17 10 Prenatal Diagnosis of Neural Tube Defects Biology of α‐fetoprotein Amniotic fluid α‐fetoprotein Amniotic fluid acetylcholinesterase Recommendations for prenatal diagnosis of NTDs using AFAFP and AChE assays Other techniques to detect neural tube defects Primary prevention of neural tube defects Complications and life expectancy References Additional references
18 11 Prenatal Diagnosis of Chromosomal Abnormalities through Chorionic Villus Sampling and Amniocentesis The incidence of chromosomal abnormalities detected by conventional cytogenetics Indications for prenatal cytogenetic diagnosis Interpretation issues: chromosome mosaicism and pseudomosaicism Interpretation issues: chromosome rearrangements Interpretation issues: chromosome polymorphisms, common inversions, and other structural variations Interpretation issues: maternal cell contamination Factors affecting diagnostic success rate and accuracy Technical standards for prenatal cytogenetics laboratories Error rates in prenatal cytogenetic diagnosis Discordance between karyotyping and molecular genetic testing Conclusion Acknowledgments References
19 12 Prenatal Diagnosis of Sex Chromosome Abnormalities Incidence Ascertainment bias Patterns of inheritance Prenatal diagnosis Turner syndrome Klinefelter syndrome Triple X and poly‐X syndromes 47,XYY males Polysomy Y karyotypes Structural abnormalities of the X chromosome Structural abnormalities of the Y chromosome Disorders of sex development Conclusion References
20 13 Prenatal Diagnosis of Chromosomal Abnormalities: From Karyotype to Microarray The study and impact of chromosome abnormalities in humans Traditional cytogenetic testing: analysis of the G‐banded metaphase Incidence and spectrum of chromosome abnormalities observed in prenatal diagnosis Rapid identification of the common aneuploidies Chromosome microarray analysis adds diagnostic yield over karyotyping and rapid aneuploidy techniques Types of microarrays Microarray design for clinical testing Interpreting and reporting of CMA results Factors affecting CMA diagnostic yield CMA in routine pregnancies CMA in pregnancies with ultrasound anomalies CMA versus karyotyping: additional points to consider CMA and genetic counseling Conclusion References
21 14 Molecular Genetics and Prenatal Diagnosis Diagnostic methods: use, limitations, and pitfalls Clinical caveats, cautions, limitations, and pitfalls Prenatal diagnosis of mitochondrial disorders Reporting incidental (secondary) results Ethical considerations in prenatal testing References
22 15 Prenatal Diagnosis of Cystic Fibrosis Genetics and epidemiology Clinical features Diagnosis Treatment Discovery of the cystic fibrosis gene Genotype–phenotype correlation Congenital bilateral absence of the vas deferens Modifier genes Ethnic variation in mutation frequencies Development and implementation of public policy for CF population carrier screening and the core mutation panel Laboratory methods Expanded panels Outcomes of the CF carrier screening program Special prenatal diagnosis situations Future directions References
23 16 Prenatal Diagnosis and the Spectrum of Involvement from Fragile X Mutations Introduction Epidemiology Clinical involvement in those with the full mutation Clinical phenotype in the premutation Pathogenesis of the premutation‐associated disorder FXTAS Molecular prenatal diagnosis methodology Preimplantation genetic testing and polar body analysis Neurobiologic advances and targeted treatment in the full mutation Genetic counseling Acknowledgments References
24 17 Prenatal Diagnosis of Fetal Malformations by Ultrasound Introduction Craniospinal defects Fetal face Pulmonary and thoracic abnormalities Cardiovascular defects Abdominal wall defects Gastrointestinal anomalies Kidneys and urinary tract anomalies Skeletal anomalies Nuchal translucency Phenotypic expression in chromosome anomalies References
25 18 Prenatal Diagnosis and Management of Abnormal Fetal Development in the Third Trimester of Pregnancy Cardiac anomalies Echogenic lung lesions Anomalies of gastrointestinal tract and abdominal wall Urinary tract anomalies Central nervous system malformations References
26 19 Prenatal Diagnosis by Fetal Magnetic Resonance Imaging Introduction MRI of the fetal central nervous system MRI of non‐CNS fetal systems Conclusion References
27 20 Prenatal Diagnosis of Skeletal Dysplasias and Connective Tissue Disorders Prenatal sonographic diagnosis of skeletal dysplasias Abnormal fetal morphology as an unexpected finding Molecular testing during pregnancy Estimating the probability of recurrence Achondroplasia, thanatophoric dysplasia, and hypochondroplasia (FGFR3 disorders) Osteogenesis imperfecta Disorders due to defects in type II collagen (achondrogenesis type 2, hypochondrogenesis, and spondyloepiphyseal dysplasia congenita) Disorders due to defects in the diastrophic dysplasia sulfate transporter gene (achondrogenesis 1B, atelosteogenesis type 2, and diastrophic dysplasia) Joint dislocations: Larsen syndrome and connective tissue disorders Marfan syndrome and Marfan overlap disorders Acknowledgments References
28 21 Prenatal Diagnosis of Disorders of Carbohydrate Metabolism Introduction Glycogen storage diseases Disorders of galactose metabolism Disorders of fructose metabolism Disorders of gluconeogenesis Pentosuria Acknowledgments References
29 22 Disorders of Metabolism of Amino Acids and Related Compounds Introduction Inborn errors of metabolism Amino acid disorders Intoxication disorders Disorders of energy production Very rare amino acid disorders Disorders of proline metabolism Disorders of renal amino acid transport In conclusion References
30 23 The Mucopolysaccharidoses: Prenatal Diagnosis, Neonatal Screening and Emerging Therapies Introduction Disease and biochemical characteristics Prenatal diagnosis Clinical characteristics and disease pathogenesis Postnatal MPS therapeutics Newborn screening Fetal considerations Future directions References
31 24 Prenatal Diagnosis of the Peroxisomal and Mitochondrial Fatty Acid Oxidation Deficiencies Introduction Mitochondrial versus peroxisomal fatty acid beta‐oxidation Mitochondrial fatty acid beta‐oxidation disorders Secondary disorders of mitochondrial fatty acid oxidation Peroxisomal fatty acid beta‐oxidation disorders Primary peroxisomal fatty acid oxidation disorders Secondary disorders of peroxisomal fatty acid oxidation References
32 25 Prenatal Diagnosis of Disorders of Lipid Metabolism Introduction Lipoprotein‐associated disorders Defects in the metabolism of glycosphingolipids GM1‐gangliosidosis/mucopolysaccharidosis IVB (Morquio B) GM2‐gangliosidoses Fabry disease Gaucher disease Metachromatic leukodystrophy Multiple sulfatase deficiency Krabbe disease (globoid cell leukodystrophy) Niemann–Pick disease Farber disease Lysosomal acid lipase deficiency: Wolman disease and cholesteryl ester storage disease The neuronal ceroid lipofuscinoses Acknowledgments References
33 26 Prenatal Diagnosis of Primary Immunodeficiency Diseases Family history Specific immune defects Lymphocyte deficiencies Antibody deficiencies Phagocyte deficiencies Defects with autoimmunity or immune dysregulation Complement deficiencies Additional syndromic immune defects References
34 27 Prenatal Diagnosis of the Hemoglobinopathies Introduction Clinical types α‐Thalassemia β‐Thalassemia Hb E disorders Sickle cell disorders Carrier screening Strategy for fetal diagnosis Approaches to prenatal diagnosis DNA diagnosis of the hemoglobinopathies Abnormal hemoglobins Diagnostic pitfalls and best practice for fetal diagnosis Summary References
35 28 Prenatal Diagnosis of Inherited Disorders of Folate and Cobalamin Metabolism Inborn errors of folate metabolism Inborn errors of cobalamin metabolism Prenatal diagnosis and fetal therapy References
36 29 Fetal Surgery Introduction Brief history of fetal surgery Ethical considerations Imaging principles for fetal intervention and surgical procedures Control of fetal pain Closed fetal therapies Conditions treated using fetoscopic procedures Congenital diaphragmatic hernia Tracheal occlusion in human fetuses Urinary tract obstruction Fetal pleural effusion Congenital cystic adenomatoid malformation Other conditions treated with fetoscopic procedures Selective termination in monochorionic gestation Open fetal surgery technique and complications Conditions treated with open fetal surgery Other potentially beneficial fetal interventions Recent advances in fetal surgery References
37 30 In Utero Stem Cell Transplantation, Enzyme Replacement, and Gene Therapy Introduction to in utero therapy In utero hematopoietic stem cell transplantation In utero enzyme replacement therapy In utero gene therapy Conclusions References
38 31 Maternal Genetic Disorders That Affect Fetal Health Introduction to inherited metabolic disorders A genetic disorder with a teratogenic effect on the fetus: phenylketonuria Genetic disorders precipitated by catabolic states including the late third trimester, intrapartum, and the puerperium: disabled protein breakdown Disorders of energy metabolism aggravated by maternal–fetal anabolic states Disorders of metal metabolism Connective tissue disorders Maternal skeletal dyplasias (chondrodystrophies) Neuromuscular disorders Hematologic disorders References
39 32 Pregnancy Termination for Genetic Disorders: Indications and Complications Introduction First‐trimester pregnancy termination techniques Second‐trimester techniques Selective abortion/fetal reduction in multiple gestations Conclusions Acknowledgments References
40 33 Providing Supportive Psychosocial Care to Parents after Perinatal Loss Introduction Perinatal Loss Complex grief after perinatal loss Highly intense grief and associated health issues Termination of pregnancy for severe or lethal fetal anomaly Needs of healthcare providers Hutti Theoretical Framework of Perinatal Grief Intensity Use of the Hutti Theoretical Framework in clinical practice Perinatal Grief Intensity Scale Communicating bad news to parents Interventions for high‐quality perinatal bereavement care Conclusion References
41 34 Prenatal Diagnosis of Fetal Infection Prenatal diagnosis of fetal toxoplasmosis Prenatal diagnosis of fetal cytomegalovirus infection Prenatal diagnosis of congenital rubella Prenatal diagnosis of fetal varicella infection Prenatal diagnosis of human parvovirus B19 infection Prenatal diagnosis of Zika virus Prenatal counseling in the midst of the SARS‐CoV‐2 pandemic Acknowledgments References
42 35 Medicolegal Aspects of Prenatal Diagnosis General concepts of medical malpractice The constitutional right of privacy in reproductive decisions The role of informed consent in medical treatment Suits for wrongful birth and wrongful life The impact of concerns about abortion on wrongful birth and wrongful life claims Future trends Summary of alleged negligent acts and outcomes in wrongful birth and wrongful life suits Statutes addressing claims for wrongful birth and wrongful life as well as abortion in the case of fetal anomaly References
43 36 Prenatal and Preimplantation Diagnosis: International Policy Perspectives Introduction Prenatal diagnosis Legal approaches Professional guidelines Preimplantation genetic diagnosis Sex selection in prenatal diagnosis and preimplantation genetic diagnosis Emerging technologies, new issues? References
44 37 Ethical Issues in the Diagnosis and Management of Genetic Disorders in the Fetus Professional ethics in obstetrics Clinical applications of professional ethics in obstetrics Ethical issues in clinical innovation and research Conclusion References
45 Index
