Genetic Disorders and the Fetus

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