FOREWORD TO THE FIRST EDITION

This is a book whose time has come. Genetic disorders and syndromes are usually thought of as being rare, and yet for affected individuals, their families, and their primary and specialty care physicians, it is essential to have reliable information about the natural history and management of the specific disorders.

The thirty conditions described in this book may seem rare (with incidences between 1 in 600 and 1 in 60,000). However, when you put together all the individuals cases or a particular condition in North America, in Europe, and in the world, a very large number of affected individual will benefit from the information in this book. In the past it has been difficult to bring together information of this type about specific disor-ders, and that is why this book fills a very important niche. It becomes a model for how to organize information that is needed for the families and primary care providers to manage the many, many other genetic disorders, congenital anomalies, and syndromes that are known to occur. The book is written in understandable language appropriate for families and for primary care and specialty physicians. It is major contribution.

Over the last two decades, remarkable progress has been made with regard to developing diagnostic tests and unravel-ing the human genome. Within the next few years all of the human genes will have been defined. The next major goal in genetics will be to understand how genes interact and func-tion, both in the course of development and over a lifetime. In addition to the remarkable progress in basic and clinical genetics, there has been increasing communication and access to information. Through the Internet, the public has access to research reports and data that were usually not readily available in the past. However, it is essential to put that information into a meaningful form and context. That is exactly what this book does. The communication explosion has allowed the networking of researchers and families. The development of parent/lay support groups has led to a cooperation between researchers and families that has helped to define the natural history and the variation that can be seen in a specific disorder.

What every family and physician wants is to provide the best care possible for the affected individual. Nobody wants to miss the opportunity for that individual to reach his or her full potential, to benefit from a useful therapy, or to avoid a complication. Parents need an understanding of what will happen over time so that they can plan. They don't want to waste money and effort going from expert to expert or doing test after test. They need a realistic approach to what they should expect both in childhood and adulthood. They also usually want to know whether there is some risk of recurrence of the condition in their other children, in other family members, and in the affected individual's offspring. They want to know whether prenatal diagnosis is available, and they want to know the spectrum of variation that can occur. The beauty of this new book is that it provides that kind of information for each specific disorder in a logical and understandable form. Most families and physicians will focus in on the chapter relevant to a specific individual. However, they can't help but glance at other chapters and see the remarkable spectrum of complications that are not present in the disorder of interest to them. They are likely to benefit from this broader perspective.

Most pediatricians will have heard of all thirty disorders; however, some primary care and specialty physicians may not have heard of a specific disorder until they have the affected individual in their practice. The book should help to alert health care professionals to consider these conditions and should lead to appropriate testing to make a correct diagnosis, reducing the time it takes to make a specific diagnosis. Two-thirds of the conditions in this book have a specific diagnostic test, but the other one-third require "pattern recognition" and an alert, trained health care professional to consider the diagnosis.

It can be expected that additional advances will be made over the next few decades leading to better understanding and better management. So this book is already dated! There is still a lot to be learned! In fact, every family and every affected individual will contribute to that increased knowledge by giving feedback to the authors. Disorder-specific parent/lay support groups will continue to play in important role in improving our understanding. The authors of each chapter have worked together with the support groups and are very aware that it is the process of working together with these groups and the members' willingness to provide information that has led to present-day understanding. We are all very grateful to each of the parents and affected individuals who have taken part in studies that have advanced our knowledge.

To write a book about management, it is necessary to know the natural history of the disorder. The authors of each of these chapters have a wealth of experience and knowledge that has been collected over the least couple of decades. Understanding the natural history not only tells us what to expect at various ages but also how to recognize various complications. It is important to understand the natural history of the condition to determine whether various therapies actually improve the outcome. It is important to understand the natural history to recognize subgroups representing the variability and heterogeneity within the disorder. It is important to understand the natural history to learn the mechanisms that lead to the disorder, e.g., what sort of gene is likely to be involved? Where is the mutation in the gene? How does that mutation relate to severity of complications? How big is the deletion? Does that size relate to severity of complications? How does this gene act against the background of other genes or pathways? Is it possible to recognize a cellular mechanism leading to this disorder? Are there parent-of-origin effects on the expression of the gene or the mutation rate? Are there hot spots that have markedly increased mutation rates? Does the place on the chromosome where the gene lies put it at increased risk for mutation? These are only a few of the questions we hope to answer over the next few decades.

No one is more motivated than the family or the affected individual to learn about these disorders. It is important for them to be as knowledgeable as possible. The families of an affected person usually know more about the condition than most of the physicians they visit. It is important for families to continue to ask questions and to gain as much knowledge as possible to ensure the best outcome for the affected individual. It is important for families and affected individuals to keep their own records about the affected individual, such as a notebook of their visits to health care facilities, copies of the reports, and the results of the tests that have been done. It is also important to keep a photographic record of changes over time.

Once a family or an affected individual becomes involved in collecting information about the disorder, they often develop quite creative ideas that challenge the standard way of thinking about the disorder. Part of the advantage of participating in a support group is that those ideas then can be shared with the medical advisors and researchers and may lead to new knowledge.

Much of our understanding of these disorders is based on the manifestations in childhood, on feeding, on growth and development, and on social skills. However, information on adults is also beginning to accumulate and has been included in this book. In some conditions there is a stable situation, in others there is improvement with aging, and in still others deterioration can be expected. For many of the conditions described in this book, behavioral patterns have been recognized.

How should a family and their primary care physician use the experts? It would be impossible for the authors of these chapters to see every individual with the condition, but it is usually helpful for a family and the affected individual to see a clinical geneticist, to visit a developmental center, or to use the multidisciplinary team that is available in their area. Over the years, specialty clinics to deal with specific conditions have been developed. At some time it is probably appropriate to visit such a clinic at least once to review the affected individual's progress and to consider any special complications or responses. On the other hand, it is very important to have a knowledgeable primary care physician who cares for day-to-day medical needs and is aware of the unique complications of the condition.

The parent/lay support groups form an international network keeping up with new information on the specific disorders, and new information is sure to come. Some new information will come through organized studies of natural history; other data will come through clinical trails of new therapies; and further information will come from basic work on cellular mechanisms and biochemical pathways. For many of these disorders animal models will be developed, such as mice with the specific disorder, so that various therapies can be considered before trails in human beings. We live in a very exciting age and can anticipate major advances over the next few decades for each of the disorders described in this book. The international network of families, affected individuals, and researchers should and will communicate about new ideas, innovative approaches, and better understanding...