Dedication -- Title page -- Copyright -- Preface -- Acknowledgements -- List of Contributors -- 1 Genetic Counseling: Preconception, Prenatal, and Perinatal -- Incidence, prevalence and burden of genetic disorders and congenital malformations -- The goal and purpose of prenatal diagnosis -- Prerequisites for genetic counseling -- Guiding principles for genetic counseling -- Preconception genetic counseling -- Genetic disorders that threaten maternal health -- Maternal genetic disorders that may threaten fetal health and survival -- Genetic disorders that pregnancy may aggravate -- A history of infertility -- Parental carrier of a genetic disorder -- A family history of a genetic disorder -- Consanguinity -- Environmental exposures that threaten fetal health -- Identification of preconception options -- Genetic counseling as a prelude to prenatal diagnosis -- Genetic counseling when the fetus is affected -- Perinatal genetic counseling -- References -- 2 Amniocentesis, Chorionic Villus Sampling, and Fetal Blood Sampling -- Introduction -- Amniocentesis -- Chorionic villus sampling -- Fetal blood sampling -- References -- 3 Amniotic Fluid Constituents, Cell Culture, and Neural Tube Defects -- Introduction -- Amniotic fluid -- Amniotic fluid cell culture -- Prenatal diagnosis of neural tube defects (NTDs) -- References -- Additional References -- 4 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 -- Conclusion -- Acknowledgments -- References -- 5 Prenatal Diagnosis of Sex Chromosome Abnormalities -- Incidence -- Patterns of inheritance -- Prenatal diagnosis -- Turner syndrome -- Klinefelter syndrome -- Triple X and poly-X syndromes -- 47,XYY males -- Structural abnormalities of the X chromosome -- Structural abnormalities of the Y chromosome -- Disorders of sex development -- Ovotesticular disorders of sex development -- Conclusion -- References -- 6 Molecular Cytogenetics and Prenatal Diagnosis -- Microdeletions -- Subtle/cryptic rearrangements -- Identification of marker chromosomes -- Structural rearrangements: duplications -- Prenatal diagnosis: interphase analysis -- Chorionic villus samples -- Interphase studies: fetal cells in maternal blood -- Interphase analysis: transcervical and uterine cavity samples -- Interphase analysis: preimplantation genetic diagnosis -- Conclusion -- References -- 7 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 -- Neurobiologic advances and targeted treatment in the full mutation -- Genetic counseling -- Acknowledgements -- References -- 8 Prenatal Diagnosis by Microarray Analysis -- History of the prenatal karyotype -- Chromosomal microarrays -- Array comparative genomic hybridization for the diagnosis of intellectual deficiency and/or multiple congenital anomalies (ID/MCA) -- Copy number variation/polymorphisms -- The blurred boundary between benign and pathogenic copy number variants.

Prenatal diagnosis by array comparative genomic hybridization -- Chromosomal rearrangements missed by array CGH -- Challenges of array CGH in a prenatal setting -- Diagnosis of miscarriages by array comparative genomic hybridization -- Preimplantation genetic diagnosis by array comparative genomic hybridization -- Conclusion -- References -- 9 Molecular Genetics and Prenatal Diagnosis -- Diagnostic methods: use, limitations and pitfalls -- Carrier detection -- Presymptomatic/predictive DNA tests -- Clinical caveats, cautions, limitations and pitfalls -- Prenatal diagnosis of mitochondrial disorders -- Reporting incidental (secondary) results -- References -- 10 Preimplantation Genetic Diagnosis -- Approaches for preimplantation genetic diagnosis -- Preimplantation genetic analysis -- Preimplantation HLA typing for transplantation treatment of genetic and acquired disorders -- Conclusion -- References -- 11 Noninvasive Prenatal Screening and Diagnosis Using Cell-free Fetal DNA -- Introduction -- Cell-free fetal DNA -- Fetal sex determination -- Fetal RHD genotyping -- Single gene disorders -- Aneuploidies -- Technical approaches to NIPT for aneuploidies -- Fetal specific targets -- Sequencing based approaches -- Discordant and inconclusive results -- Ethical and counseling issues -- Summary -- References -- 12 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 DS, NTD, and unaffected pregnancies -- Risk screening for Down syndrome -- Age-specific DS risk at term -- DS risk at the time of the test -- DS likelihood ratios -- Modeling performance of DS screening -- Established multi-marker DS policies -- Model performance of NTD screening.

Prospective confirmation of DS model -- Further multimarker DS strategies -- Genetic sonogram -- Repeat measures and highly correlated markers -- Ultrasound screening for open spina bifida -- Other DS markers -- Clinical factors -- Edwards syndrome (trisomy 18) -- Other conditions associated with altered markers -- Planning a program -- Conclusion -- Acknowledgements -- Note -- References -- 13 Prenatal Diagnosis of Fetal Malformations by Ultrasound -- Common defects amenable to prenatal diagnosis in the second trimester of pregnancy -- Detection of abnormalities in the first trimester of pregnancy -- Ultrasonographically detectable markers of fetal chromosomal defects in the first trimester -- Three- and four-dimensional ultrasound -- Phenotypic expression of fetal aneuploidies in the second trimester -- Incidence of abnormalities in common chromosomal defects -- Fetal abnormalities with chromosomal defects -- Multiple pregnancies -- References -- 14 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 -- Abdominal wall defects -- Urinary tract anomalies -- Central nervous system malformations -- References -- 15 Prenatal Diagnosis by Fetal Magnetic Resonance Imaging -- Introduction -- MRI of the fetal CNS -- MRI of non-CNS fetal systems -- Conclusion -- References -- 16 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) -- Prenatal diagnosis -- 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 -- 17 Prenatal Diagnosis of Cystic Fibrosis -- Genetics and epidemiology -- Clinical features -- Diagnosis -- Treatment -- Discovery of the CF gene -- The CFTR gene and its protein product -- CFTR mutations and variants -- 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 -- Acknowledgments -- References -- 18 Prenatal Diagnosis of the Hemoglobinopathies -- Introduction -- Clinical types -- The globin genes -- α-Thalassemia -- β-Thalassemia -- Hb E disorders -- Sickle cell disorders -- Carrier screening -- Approaches to prenatal diagnosis -- DNA diagnosis of the hemoglobinopathies -- Abnormal hemoglobins -- Diagnostic pitfalls and best practice for fetal diagnosis -- Fetal DNA diagnosis: guidelines for best practice -- References -- 19 Prenatal Diagnosis of Primary Immunodeficiency Diseases -- Family history -- Specific immune defects -- Lymphocyte deficiencies -- Antibody deficiencies -- Phagocyte deficiencies -- Complement deficiencies -- Unclassified deficiencies -- References -- 20 Prenatal Diagnosis of Disorders of Lipid Metabolism -- Introduction.

Lipoprotein-associated disorders.