To give you the bottom line first: this book is a masterpiece written by numerous masters who are able to `speak different languages' and who bridge disciplines from developmental biology, normal and abnormal morphogenesis, and molecular biology, to clinical genetics and dysmorphology. Understanding developmental biology is a crucial requirement for those working in clinical genetics; and the two fields are now coming together through advances in the Human Genome Project and in elucidating the genetic basis of various genetic disorders. I myself feel privileged both to work with families who have a child with a severe birth defect and at the same time to direct a laboratory whose research focuses on identifying the underlying basis of normal and abnormal embryonic development in humans.
Our knowledge of developmental pathways is still in its infancy compared with what is known about biochemical pathways. The editors have accomplished a monumental task by putting together chapters on the large number of human multiple malformation syndromes that are known about and organizing them within developmental pathways. This is the first time human developmental disorders have been covered in this way in a textbook. As mentioned in the preface, the idea for Inborn Errors of Development was influenced by Garrod's concept of inborn errors of metabolism, which has been expanded on here to inborn errors of development. If the goal of this book is to integrate clinical genetic disorders with molecular findings to place these in the context of development, it is a goal that has been clearly accomplished. This does not come as a surprise, as all of three editors, and many of the contributing authors, are clinicians as well as bench scientists.
The book begins with an overview of some general concepts, with introductory chapters on approaches to understanding congenital malformations,general principles of differentiation and morphogenesis, and the role of model organisms in understanding development. The chapters that follow detail patterns of development of various organ systems. Most of the chapters of this book are devoted to over 100 clinical genetic disorders for which the underlying causes have been identified. These include disorders caused by anomalies in genes such as sonic hedgehog (SHH), WNT,transforming growth factor β, tumour necrosis factor, fibroblast growth factor receptor and Notch. Disorders that are caused by mutations in genes or gene families that have uncertain or unknown positions in a developmental pathway include members of the HOX, PAX, Forkhead and the T-box gene families. The book concludes with chapters on numerous genetic disorders that are caused by changes in genes that encode proteins involved in the regulation of chromatin structure and gene expression, and in transcription,post-translational control and ubiquination, and in those that encode guanine nucleotide-binding proteins, kinases and phosphatases. Many of the disorders resulting from mutations in the latter are tantalizing, as they affect multiple organ systems in common and rare dysmorphic syndromes. Only now that their underlying molecular basis is known, does the combination of clinical findings make sense.
An area close to my own research interest is cholesterol biosynthesis and SHH signaling, which is very well covered in this book. SHH signaling is a prime example of a well-defined pathway that is critically important during early embryogenesis and is specifically required in limb and brain development. As the book discusses, abnormal SHH signaling can lead to disorders that affect different organ systems, such as Smith-Lemli-Opitz syndrome, a birth defect that is caused by abnormal cholesterol biosynthesis. Loss of function of SHH can cause the most common forebrain anomaly in humans,holoprosencephaly. Loss of function of PATCHED1, the receptor for SHH, leads to basal cell nevuscarcinoma or Gorlin syndrome. And distinct disorders with anomaliesof the hands and feet, such as Pallister-Hall and Greig Cephalopolysyndactyly syndromes, are caused by mutations in GLI3,another gene in the SHH signaling pathway.
This book is written for health professional and basic scientists alike. I learned that it is already used as a textbook in developmental biology classes. As the director of medical genetics training at NIH, I will recommend this book to clinical and PhD fellows in my program. At the same time, I also recommend it to the connoisseurs of dysmorphology – my colleagues from the David W. Smith Workshop on Malformations and Morphogenesis. I have no doubts that this book will become one of the standard textbooks, comparable with (yet uniquely different from) other classics by Jones, Scriver et al. and Gilbert (Jones, 1997; Scriver et al., 2001; Gilbert, 2000).