**Meet the editors**

Dr Richard K. W. Choy obtained his BSc degree in Biomedical Sciences from the University of Bradford and M(Med)Sc in Immunology at University of Birmingham, UK. He received postgraduate training in research and was awarded Doctor of Philosophy by The Chinese University of Hong Kong in 1999. Dr Choy's main research interests include the development of novel molecular

diagnostic strategies and innovative applications of molecular analysis tools in prenatal diagnosis. His current research focuses on the development of the microarray based Comparative Genomic Hybridization (array CGH) and massive parallel sequencing for prenatal diagnosis. In terms of professional service, Dr Choy is an Honorary Scientific Officer (medical) at the New Territories East Cluster of Hospitals, Hong Kong, where he is involved in the delivery of the laboratory diagnostic service. He is also the board member of the Hong Kong Society of Medical Genetics since 2009.

Tak Yeung Leung is Professor in the Maternal Fetal Medicine unit in the Department of Obstetrics and Gynaecology of The Chinese University of Hong Kong. His special interest is in perinatal medicine, prenatal screening and diagnosis of fetal abnormalities, with advanced genetic and ultrasound technology, including the non-invasive prenatal diagnosis using maternal

cell-free fetal DNA and array comparative genomic hybirdisation. He has published more than 150 papers in international peer reviewed journals. He is also invited into the editorial board of international journals suchas American Journal of Perinatology and Pediatric Research (Fetus & Pregnancy Section). Besides, Professor Leung has strong international and Asian-Pacific connection with appointments in several international professional bodies including: Chairman of the Prenatal Maternal Screening Special Interest Group of International Society for Prenatal Diagnosis, Foundation Broad member of Global Obstetric Network (GONet), Foundation Secretary of The Chinese Fetal Medicine Foundation. He is also the Vice-president of Obstetrical and Gynaecolgical Society of Hong Kong, and co-opt council member of Hong Kong College of Obstetricians and Gynaecologists. Professor Leung is enthusiastic in teaching and training and is the organizer as well as trainer in many traning courses such as first trimester ultrasound, ALSO and PROMPT.

Contents

**Preface IX** 

Chapter 1 **Invasive Prenatal Diagnosis 1** 

**Hypophosphatasia 27**  Atsushi Watanabe, Hideo Orimo,

Chapter 3 **Skeletal Dysplasias of the Human Fetus: Postmortem Diagnosis 33**  Anastasia Konstantinidou

**Isolated Macrodactyly 59** 

Chapter 6 **Normal and Abnormal Fetal Face 85**  Israel Goldstein and Zeev Wiener

**Short Femurs 71** 

Chapter 9 **Real-Time Quantitative PCR for** 

Sonja Pop-Trajković, Vladimir Antić and Vesna Kopitović

Chapter 2 **Prenatal Diagnosis of Severe Perinatal (Lethal)** 

Toshiyuki Takeshita and Takashi Shimada

Chapter 4 **Prenatal Sonographic Diagnosis and Evaluation of** 

Chapter 5 **Prenatal Evaluation of Fetuses Presenting with** 

Chapter 7 **Current Issues Regarding Prenatal Diagnosis of** 

Maria Luís Cardoso, Mafalda Barbosa, Ana Maria Fortuna and Franklim Marques

Chapter 8 **Understanding Prenatal Iodine Deficiency 137** 

**Detection Cell Free Fetal DNA 163**  Tuba Gunel, Hayri Ermis and Kilic Aydinli

Hande Yağmur, Atıl Yüksel and Hülya Kayserili

Funda Gungor Ugurlucan, Hülya Kayserili and Atil Yuksel

**Inborn Errors of Cholesterol Biosynthesis 111** 

Inés Velasco, Federico Soriguer and P. Pere Berbel

## Contents

#### **Preface XI**


## Preface

As new technological innovations arise, clinical medicine must also adapt and assimilate these advances into clinical practice. Prenatal diagnosis is no exception. When amniocentesis was introduced into practice, study of the unbanded chromosomes was the standard. With the introduction of G-banded analysis, duplications, deletions, and gross chromosomal translocations were detectable. By comparing the phenotypic to the genotypic findings, most of the detected chromosomal aberrations were quickly found to be clinically relevant. Integrating this new information into patient care and counseling required years of data gathering and analysis. As clinical and molecular technologies continued to evolve, similar questions concerning the appropriate clinical use of these technologies in prenatal diagnosis have also arisen.

*Prenatal Diagnosis: Morphology Scan and Invasive Methods* brings together distinguished contributors with extensive experience in the fetal ultrasound and prenatal diagnosis fields. Emphasis has been paid to the inclusion of molecular and sonographic techniques used in fetal medicine that are relevant to obstetricians and scientists performing prenatal diagnosis. These include how to diagnose iodine deficiency, skeletal dysplasisa; methods for molecular diagnosis of fetal diseases and treatment by fetal therapy. We hope that this book will be an invaluable reference for obstetricians and scientists in the process of prenatal diagnosis.

#### **Richard Kwong Wai Choy and Tak Yeung Leung**

The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China

**1** 

*Serbia* 

**Invasive Prenatal Diagnosis** 

*1Clinic for Gynecology and Obstetrics, Clinical center of Niš* 

Sonja Pop-Trajković1, Vladimir Antić1 and Vesna Kopitović<sup>2</sup>

Prenatal diagnosis, traditionally used as a synonymous for invasive fetal testing and evaluation of chromosomal constellation, presently encompasses many other issues like pedigree analyses, fetal risk assessment, population screening, genetic counseling and fetal diagnostic testing as well. Ultrasound guided chorionic villus samling (CVS), amniocentesis and, to a lesser extent, fetal blood sampling are used routinely in fetal medicine units. Other fetal tissue biopsies such as skin, liver and muscle biopsy are used only rarely. In this chapter we discuss the invasive diagnostic procedures in maternal fetal medicine with specific interest of showing the list of indications basic principles used for choosing the particular invasive technique, linkage of non invasive with invasive diagnostic procedures, precise description of techniques, list of complications and their prevention and management, all of these based on the recent scientific results and clinical experiences

The ability to sample and analyse villus tissue was demonstrated in China, in 1975 (Department of Obstetrics and Gynecology THoAIaSCA, 1975). Trying to develop a technique for fetal sex determination, Chinese inserted a thin catheter into the uterus guided only by the tactile sensation and small pieces of villi were aspirated. By today's standards of ultrasonically guided invasive procedures this approach seems crude, but their diagnostic accuracy and low miscarriage rate demonstrated the feasibility of first-trimester sampling. Major advancements have occurred since that time in instrumentation, techniques for direct kariotyping, faster culturing of cells and in the molecular and biochemical assay of chorionic villi. Today in experienced centers, chorionic villus sampling (CVS) as a method of obtaining chorionic villi using transcervical or transabdominal approach, can be utilized as a primary prenatal diagnostic tool. Although CVS has the advantage of being carried out very early in pregnancy to the widespread amniocentesis, due to, more likely, the more technically demanding aspects

CVS is usually performed between 10 and 12 weeks of pregnancy. The risk and severity of limb deficiency appear to be associated with the timing of CVS: the risk before the end of 10

of sampling, CVS has still not replaced amniocentesis in many centers.

**1. Introduction** 

publicized in the available literature.

**2. Chorionic villus sampling** 

**2.1 Timing and technique** 

*2Clinic for Gynecology and Obstetrics, Clinical Center of Vojvodina* 
