Fetal Morph Functional Diagnosis

Preface
Contents
Part I: Ultrasound Examination
	Chapter 1: Ultrasonic Screening
		1.1 Introduction
		1.2 Late First-Trimester Anomaly Scan (at 11–13 Weeks)
			1.2.1 Aims of the First-Trimester Anomaly Scan
			1.2.2 Equipment Used
			1.2.3 Pre-examination Requirements
				1.2.3.1 Head
				1.2.3.2 Thorax
				1.2.3.3 Abdomen
				1.2.3.4 Extremities
				1.2.3.5 Abnormal Fluid Collection
		1.3 Mid-trimester Anomaly Scan (at 18–20 Weeks)
			1.3.1 Head
			1.3.2 Face
			1.3.3 Chest and Heart
			1.3.4 Abdomen
			1.3.5 Spine
			1.3.6 Extremities
			1.3.7 Amniotic Fluid
		1.4 Early Third-Trimester Anomaly Scan (28–30 Weeks)
			1.4.1 Head
			1.4.2 Face
			1.4.3 Chest and Heart
			1.4.4 Abdomen
			1.4.5 Spine
			1.4.6 Extremities
			1.4.7 Amniotic Fluid
		1.5 Summary
		References
	Chapter 2: Abnormal Findings in Ultrasound Examination
		2.1 Introduction
		2.2 Head and Neck
			2.2.1 Neural Tube Defects
				2.2.1.1 Anencephaly
			2.2.2 Myelomeningocele
			2.2.3 Holoprosencephaly
			2.2.4 Ventriculomegaly
			2.2.5 Cystic Hygroma and Lymphangioma
		2.3 Thorax
			2.3.1 CPAM and BPS
			2.3.2 Congenital Diaphragmatic Hernia
			2.3.3 Cardiovascular Disease
		2.4 Abdomen
			2.4.1 Abdominal Wall Defects
			2.4.2 Gastrointestinal Malformations
				2.4.2.1 Esophageal Atresia
				2.4.2.2 Duodenal Atresia
		2.5 Kidney and Urinary Tract
			2.5.1 Urinary Tract Dilatation
			2.5.2 Dysplastic Kidneys
		2.6 Skeleton
		2.7 Ultrasound Features of Chromosomal Abnormalities
			2.7.1 Trisomy 21
			2.7.2 Trisomy 18
			2.7.3 Trisomy 13
			2.7.4 Turner Syndrome
		References
	Chapter 3: Fetal MRI
		3.1 Introduction
			3.1.1 The Advantages of MRI
			3.1.2 The Disadvantages of MRI
		3.2 MRI Sequences
			3.2.1 T2-Weighted Sequences
			3.2.2 Thick-Slab Imaging
			3.2.3 Steady-State Free-Precession Sequences
			3.2.4 T1-Weighted Sequences
			3.2.5 Echoplanar Imaging
			3.2.6 Diffusion-Weighted Imaging
			3.2.7 Three-Dimensional Dataset for Reconstruction
		3.3 MRI Indications
			3.3.1 Approach to the Central Nervous System
			3.3.2 Approach to the Face and Neck
			3.3.3 Approach to the Chest
			3.3.4 Approach to the Heart
			3.3.5 Approach to the Abdominal Wall and Gastrointestinal Tract
			3.3.6 Approach to Genitourinary Tract
			3.3.7 Approach to the Extremities and Bone
			3.3.8 Approach to Complex Malformation
		References
Part II: Genetic Tests
	Chapter 4: Prenatal Screening for Fetal Aneuploidy
		4.1 Tests That Estimate the Incidence Rates of Fetal Chromosomal Diseases
		4.2 Fetal Chromosome Tests Using Maternal Plasma cfDNA
		4.3 Accuracy of Prenatal Screening Tests
		4.4 Ethical Aspects of Prenatal Screening Tests
		References
	Chapter 5: Diagnostic Tests (Invasive Procedures)
		5.1 Chorionic Villus Sampling (Fig. 5.1)
			5.1.1 Approaches for CVS
			5.1.2 Twin Pregnancies
			5.1.3 Chromosomal Mosaicism
			5.1.4 Maternal Cell Contamination
		5.2 Amniocentesis (Fig. 5.2)
			5.2.1 Placental Puncture
			5.2.2 Twin Pregnancies
			5.2.3 Early Amniocentesis
		5.3 Cordocentesis
			5.3.1 Confirming That Blood Is of Fetal Origin
		5.4 Other Diagnostic Tests
			5.4.1 Maternal Infections
			5.4.2 Rh Isoimmunization
			5.4.3 Maternal Risk
		References
Part III: Genetic Disorders
	Chapter 6: Mendelian Disease
		6.1 Mendelian Law
			6.1.1 Discovering the Law of Dominance
			6.1.2 Discovering the Law of Segregation
			6.1.3 Discovering the Law of Independence
		6.2 Mendelian Disease
			6.2.1 Autosomal Dominant Disease
			6.2.2 Autosomal Recessive Disease
			6.2.3 X-Linked Recessive Disease
			6.2.4 X-Linked Dominant Diseases
		6.3 Cases Not Applicable to Mendelian Law of Segregation
			6.3.1 Decrease in Penetration
			6.3.2 Difference in Expression
			6.3.3 Gonad Mosaic
			6.3.4 Difference in Age of Onset
			6.3.5 Genetic Heterogeneity
		Further Reading
	Chapter 7: Neuroimaging and Genetics in Brain Maldevelopment
		7.1 Introduction
		7.2 Cranial Dysraphism (Neurulation Disorder)
		7.3 Holoprosencephaly (Prosencephalic Disorder)
		7.4 Agenesis of the Corpus Callosum
		7.5 Malformations of Cortical Development (Disorders of Proliferation, Migration, and Post-migration)
		7.6 Ventriculomegaly
		7.7 In Utero Brain Injury and Damage
		7.8 Future Perspective
		References
	Chapter 8: Muscular Dystrophy
		8.1 Introduction
		8.2 Genetic Causes of Muscular Dystrophy
		8.3 Diagnosis and Clinical Management of Muscular Dystrophies
		8.4 Recent Progress in Treatments for Muscular Dystrophy
		8.5 Ethical Standards for the Prenatal Diagnosis of Muscular Dystrophy
		8.6 Prenatal Genetic Testing
			8.6.1 Duchenne Muscular Dystrophy
				8.6.1.1 Molecular Genetic Testing
				8.6.1.2 Prenatal Diagnosis
				8.6.1.3 Preimplantation Diagnosis
			8.6.2 DM1
				8.6.2.1 Molecular Genetic Testing
				8.6.2.2 Prenatal Diagnosis
				8.6.2.3 Preimplantation Diagnosis
			8.6.3 FCMD
				8.6.3.1 Molecular Genetic Diagnosis
				8.6.3.2 Prenatal Diagnosis
				8.6.3.3 PGT
		8.7 Summary
		References
	Chapter 9: Skeletal Dysplasia
		9.1 Introduction
		9.2 Ultrasonic Characteristics
		9.3 Detection of Bone Abnormalities
			9.3.1 Observation and Measurement of Long Bones
			9.3.2 Observation of Other Bones
			9.3.3 Abnormal Findings of Long Bone
		9.4 Skeletal Dysplasias
			9.4.1 Thanatophoric Dysplasia
			9.4.2 Achondroplasia
			9.4.3 Achondrogenesis
			9.4.4 Osteogenesis Imperfecta Type II/III
			9.4.5 Osteogenesis Imperfecta Type I/IV
			9.4.6 Asphyxiating Thoracic Dysplasia
		9.5 Conclusions
		References
	Chapter 10: Genitourinary Tract Abnormalities
		10.1 Fetal Ultrasound Imaging of the Normal Genitourinary Tract
		10.2 Fetal Ultrasound Imaging of Genitourinary Tract Abnormalities
			10.2.1 Kidney
			10.2.2 Lower Urinary Tract
			10.2.3 Adrenal Gland
			10.2.4 Genitalia
		References
	Chapter 11: Genomic Imprinting Disorders (Including Mesenchymal Placental Dysplasia)
		11.1 Genomic Imprinting
			11.1.1 Imprinted Genes and Differentially Methylated Regions (DMRs)
			11.1.2 Regulation of Imprinted Gene Expression
			11.1.3 Imprinted Gene Network (IGN)
		11.2 Imprinting Disorders (IDs)
			11.2.1 Clinical Characteristics of IDs
			11.2.2 Molecular Mechanisms of IDs
			11.2.3 Multi-locus Imprinting Disturbance (MLID)
			11.2.4 Assisted Reproductive Technology (ART) and IDs
		11.3 Hydatidiform Mole
		11.4 Placental Mesenchymal Dysplasia (PMD)
			11.4.1 Definition of PMD
			11.4.2 Fetomaternal Complications of PMD
			11.4.3 Imaging and Serum Markers for PMD
			11.4.4 Gross, Histopathological, and Immunohistochemical Findings of PMD
			11.4.5 Molecular Pathogenesis of PMD
		References
	Chapter 12: Genetics in Multiple Gestation
		12.1 Introduction
		12.2 Zygosity and Chorionicity
			12.2.1 Dizygotic Monochorionic (DZ-MC) Twin Pregnancy
			12.2.2 DZ Twin After a Single Embryo Transfer
			12.2.3 DCDA Twins After a Single Blastocyst Embryo Transfer
		12.3 Prenatal Ultrasound Diagnosis of Chorionicity and Amnionicity
			12.3.1 Diagnosis of Chorionicity
			12.3.2 Diagnosis of Amnionicity
		12.4 Pitfalls of Chorionicity, Amnionicity, and Zygosity
			12.4.1 Lambda Sign Does Not Necessarily Guarantee DCDA Twin
			12.4.2 Discordant Fetal Sex Does Not Always Indicate DCDA Twin
			12.4.3 MCDA Twin with Separate Placenta Does Exist
			12.4.4 Two Yolk Sacs Do Not Determine MCMA Twin Any More
		12.5 Role of Vascular Anastomoses in Monochorionic Placenta
		References
	Chapter 13: Fetal Therapy
		13.1 IUTx
		13.2 IUGT
		13.3 Advantages of Fetal Stem Cell Transplantation and Gene Therapy
		13.4 Disadvantages of Fetal Stem Cell Transplantation and Gene Therapy
		13.5 Academic Movement on IUTx and IUGT
		13.6 Summary
		References
Part IV: Chromosomal Diseases
	Chapter 14: General Remarks About Autosomal Diseases
		14.1 Chromosomal Abnormalities
		14.2 Autosomal Dominant Diseases
		14.3 Autosomal Recessive Diseases
		14.4 Imprinting Diseases
		References
	Chapter 15: Sex Chromosome-Linked Diseases
		15.1 X Chromosome Copy-Number Variation
			15.1.1 X Chromosomal Microdeletion Syndrome
				15.1.1.1 Xp22.3 Deletion Syndrome
					Leri–Weill Syndrome
					Chondrodysplasia Punctate 1
					X-Linked Ichthyosis
					Kallmann Syndrome 1
				15.1.1.2 Xp11.3 Deletion
					Xp11.3 Deletion Includes MAOA and MAOB
					Xp11.3 Deletion Includes RP2
				15.1.1.3 Xq21 Deletion Includes CHM and POU3F4
				15.1.1.4 Xq28 Deletion Includes RAB39B
			15.1.2 X Chromosomal Duplication Syndrome
				15.1.2.1 Xp11.22p11.23 Recurrent Duplication Includes SHROOM4
				15.1.2.2 Xp11.22 Duplication Includes HUWE1
				15.1.2.3 Xq26.3 Duplication Includes GPR101
				15.1.2.4 Xq27.3q28 Duplication Includes FMR1
				15.1.2.5 Xq28 Duplication
					Xq28 Duplication Includes GDI1
					Xq28 Duplication Includes RAB39B
					Xq28 Duplication Includes MECP2
		15.2 X-Linked Monogenic Disorders
			15.2.1 X-Linked Adrenoleukodystrophy Caused by Mutations of ABCD1
			15.2.2 Menkes Syndrome Caused by Mutations of ATP7A
			15.2.3 X-Linked Alport Syndrome Caused by Mutations of COL4A5
			15.2.4 Duchenne/Becker Muscular Dystrophy (DMD/BMD) Caused by Mutations of DMD
			15.2.5 Fragile X Syndrome Caused by Premutation of FMR1
			15.2.6 Hemophilia A Caused by Mutations of HEMA
			15.2.7 Lesch–Nyhan Syndrome Caused by Mutations of HPRT1
			15.2.8 X-Linked Severe Combined Immunodeficiency Caused by Mutations of IL2RG
			15.2.9 Oral-Facial-Digital Syndrome Type 1 Caused by Mutations of OFD1
			15.2.10 X-Linked Hypophosphatemia Caused by Mutations of PHEX
			15.2.11 Immunodeficiency with Hyper-IgM Caused by Mutations of TNFSF5
		15.3 Y-Linked Disorders and Genetic Mechanisms
			15.3.1 Male Infertility and AZF Loci Microdeletions
				15.3.1.1 Genes and Deletions in AZFa
				15.3.1.2 Genes and Deletions in AZFb
					Single-Copy Genes
					Gene Families
				15.3.1.3 Genes and Deletions in AZFc
			15.3.2 DSD and Mutation/Translocation of SRY
		References
Part V: Genetic Counseling
	Chapter 16: Fetal Anomaly and Genetic Counseling
		16.1 Introduction
		16.2 Ultrasonography for Chromosomal Abnormalities and Copy Number Variation
		16.3 Ultrasonography for Monogenic Diseases
		16.4 Ultrasonography for Multifactorial Diseases
		16.5 Pretest Genetic Counseling
		16.6 Post-Test Counseling
		16.7 Conclusion
		References
	Chapter 17: Soft Marker Test (NT, Nasal Bone, Etc.) and Genetic Counseling
		17.1 Introduction
		17.2 Soft Markers
		17.3 Soft Markers and the Future
		17.4 Application of Soft Markers in Twin Pregnancies
		17.5 Genetic Counseling
		References
	Chapter 18: Noninvasive Prenatal Testing and Genetic Counseling
		18.1 Introduction
		18.2 NIPT for Aneuploidy Screening
			18.2.1 NIPT and Guidelines
			18.2.2 Where Does cffDNA Come from?
			18.2.3 Accuracy
			18.2.4 Present and Future of NIPT
		18.3 NIPT and Genetic Counseling
			18.3.1 Genetic Counseling for Perinatal Care
			18.3.2 The Goal of Genetic Counseling for NIPT
			18.3.3 Genetic Counseling for Positive Result
		18.4 Conclusion
		References
	Chapter 19: Trisomy and Genetic Counseling
		19.1 Advanced Maternal Age and Fetal Trisomy
		19.2 Prenatal Diagnostic Testing for Fetal Trisomy
		19.3 Genetic Counseling Following a Prenatal Diagnosis of Trisomy
			19.3.1 Trisomy 21 (Down Syndrome)
			19.3.2 Trisomy 18 (Edwards’ Syndrome) and Trisomy 13 (Patau Syndrome)
			19.3.3 Trisomy X (47,XXX)
			19.3.4 Klinefelter Syndrome (47,XXY)
			19.3.5 XYY
		19.4 Decision-Making Following a Prenatal Diagnosis of Trisomy
		References
	Chapter 20: Sex Chromosome Abnormalities and Genetic Counseling
		20.1 Introduction
		20.2 Characteristics of Sex Chromosomes
		20.3 Turner Syndrome and Variants
		20.4 Klinefelter Syndrome
		20.5 XXX Female
		20.6 XYY Male
		20.7 Genetic Counseling for Sex Chromosome Abnormalities
		References
	Chapter 21: Genetic Counseling: Chromosomal Structural Rearrangements
		21.1 What Are the Chromosomal Structural Rearrangements Identified During the Fetal Period?
		21.2 Balanced Structural Rearrangements
			21.2.1 Reciprocal Translocation
			21.2.2 Whole Arm Translocation
			21.2.3 Robertsonian Translocation/Isochromosomes
			21.2.4 Inversion
			21.2.5 Balanced Insertion
		21.3 Unbalanced Structural Rearrangements
			21.3.1 Small Supernumerary Marker Chromosomes (sSMCs)
			21.3.2 Additional Chromosomes and Unbalanced Translocations
			21.3.3 Unbalanced Robertsonian Translocations
			21.3.4 Deletion, Duplication, Insertion, Inverted Insertion
			21.3.5 Ring Chromosomes
			21.3.6 Uniparental Disomy
		21.4 Mosaicism
			21.4.1 Complex Chromosomal Rearrangements (CCRs)
		21.5 Others
			21.5.1 X-Autosomal Translocation
			21.5.2 Y-Autosomal Translocation
			21.5.3 X-Y Translocations
				21.5.3.1 Xp-Yq Translocation: t(X;Y)(p22.3;q11)
				21.5.3.2 Xp-Yp Translocation: t(X;Y)(p22.3;p11)
				21.5.3.3 Xq-Yq Translocation: t(X;Y)(q28;q11.21)
		21.6 Chromosomal Variants
		21.7 Chromosome Abnormalities and Selection
		21.8 Key Points in Genetic Counseling for Chromosomal Structural Rearrangements in Fetus
		References
	Chapter 22: Gene Disorders and Genetic Counseling
		22.1 Introduction
		22.2 Human Genome, Genes, Alleles, and Polymorphism
		22.3 Mendelian Disorders
			22.3.1 Autosomal Dominant Inheritance
			22.3.2 Autosomal Recessive Inheritance
			22.3.3 X-Linked Inheritance
		22.4 Nonmendelian Disorders
			22.4.1 Triplet Repeat Diseases
			22.4.2 Imprinting Diseases
			22.4.3 Mitochondrial Inheritance
			22.4.4 Germline Mosaicism and Chimerism
		22.5 Conclusion
		References
Part VI: Technical
	Chapter 23: G-Banding: Fetal Chromosome Analysis by Using Chromosome Banding Techniques
		23.1 The Procedure of the Chromosome Analysis by G-banding
		23.2 Chromosome Banding
		23.3 Precise Investigation of Mosaicism and Points of That Interpretation
		23.4 Points to Care in the Interpretation of Chromosomal Aberrations
		23.5 Normal Chromosome Variants
		23.6 Conclusion
		References
	Chapter 24: FISH
		24.1 Rapid Prenatal Diagnosis of Aneuploidies by FISH
		24.2 Aneuploidy in Human Spermatozoa: FISH Analysis in Men with Constitutional Chromosomal Abnormalities
		24.3 Multicolored Spectral Karyotyping for Complex Chromosomal Rearrangements
		References
	Chapter 25: Polymerase Chain Reaction (PCR)
		25.1 The Technical Advantages of Polymerase Chain Reaction in Prenatal Diagnosis
		25.2 The PCR Procedure (Fig. 25.1)
		25.3 Clinical Use of PCR in Prenatal Diagnosis
			25.3.1 PCR in Invasive Prenatal Genetic Testing
			25.3.2 PCR in Noninvasive Prenatal Genetic Testing
		References
	Chapter 26: Microarray and Next Generation Sequencing
		26.1 Introduction
		26.2 Microarray
		26.3 Next Generation Sequencing
		26.4 Future Perspectives
		References
	Chapter 27: How to Obtain Certifications and Licenses for Prenatal Diagnosis
		27.1 How to Qualify for Prenatal Diagnosis in Japan
			27.1.1 Qualifications
			27.1.2 History and Present Status
		27.2 Qualification for Prenatal Diagnosis in Other Countries
			27.2.1 Prenatal Testing
			27.2.2 Genetic Counseling
		27.3 Summary and Future Considerations
		References