Almost a generation has gone by since Management of Genetic Syndromes was conceived and the first edition published. That volume provided up‐to‐date, expert‐authored, practical information on clinical features, natural history, medical concerns, and management of 30 conditions, each with an incidence between 1/600 and 1/60,000. Thus, most were considered rare conditions, and unlikely to be on the radar of primary care practitioners or non‐genetics specialists unless/until that physician had an affected individual in their practice. Most, if not all, chapter authors had worked closely for many years with a family support group, accumulating a wealth of knowledge on the myriad associated medical consequences and natural history. While diagnostic testing was available for about two‐thirds, the remaining conditions could only be diagnosed by recognition of a pattern that might include congenital anomalies, differences in stature, appearance and/or development, and specific health problems.

Over the course of the last 20 years, enormous changes have occurred in the technologies available for testing and interpretation of results, the way we approach pattern recognition as it applies to differences in appearance, the options for management and, occasionally, treatment of associated health concerns, and, perhaps most importantly, the way the medical profession and society view rare diseases. In short, nothing is the same!

Technology has moved away from analysis of chromosomes and individual genes to testing of the genome using microarrays and whole exome and whole genome sequencing. When a diagnosis is suspected, focused testing remains the gold standard. However, ordering a test that evaluates multiple genes that cause conditions with overlapping features, or screening the patient’s entire genome if a testable diagnosis is not suspected, is now not only possible but increasingly cost effective. Clinical diagnosis relies on painstaking assessment and recognition of specific physical differences, the phenotype. It is just as important to describe that phenotype in an accurate and consistent manner. The development of a human phenotype ontology with more than 10,000 terms, each of which describes a phenotypic variation seen in human disease, is of great importance for the classification and comparison of affected individuals. Recognition of differences in facial appearance, some quite subtle, has moved from an “art” to a “science”. Initially grounded in the experience and observation skills of the clinician, pattern recognition was enhanced by simple linear measurements and then revolutionized by 3D photography, computer modeling, machine learning, and artificial intelligence. Syndrome recognition aided by the use of images taken by a point‐and‐shoot camera or even a mobile phone now has an established place in clinical practice.

Over the last 20 years, there has been increasing recognition that rare diseases, in aggregate, are common, and estimated to affect 200 million people worldwide. A substantive proportion of the approximately 7000 known rare diseases are due to the altered function of single genes. For an individual with a rare genetic disease, timely provision of a molecularly confirmed diagnosis is critical for many reasons. It shortens the diagnostic odyssey, improves disease management by identifying specific health risks and preventing unnecessary or harmful diagnostic interventions and treatments, and it enables recurrence risk counseling and reproductive choice. This is the cornerstone of precision medicine. Understanding how genes function and interact and concomitant insight into biological mechanisms will not only enhance diagnosis and medical care for individuals with rare diseases, but will transform our understanding of health and disease. Documentation of pathogenic variations in the same gene in at least two unrelated individuals with the same rare disease is necessary to confirm the identity of a novel disease gene. As we study diseases of increasing rarity, a single academic centre or program is unlikely to achieve this standard. Thus diagnosis (and treatment) of individually rare disorders is best addressed by broad international collaboration. To this end, the International Rare Diseases Research Consortium (IRDiRC) was established in 2011, just a year after publication of the third edition of Management of Genetic Syndromes. It now brings together nearly 50 organizations in 18 countries invested in rare disease research. In addition to enabling the formation of scientific groups focused on diagnostics and therapies, close association with private‐sector pharmaceutical and biotechnology companies has increased funding, data discovery and data sharing. International databases for genotype‐driven and phenotype‐driven matching of individuals with unsolved rare diseases have been developed, with an overarching platform that connects the data silos. Critically, partnership with national and continental patient advocacy organizations from Africa, Asia, Australia, Europe, and North America ensures the gene discovery research remains grounded in patient/family experience and relevance.

This fourth edition of Management of Genetic Syndromes includes five new conditions, bringing the total to 63 and more than doubling the original cohort of disorders. The thoughtful and consistent layout is unchanged, as it has proved to be a popular, effective, easy to use format. Since individuals with syndromes will be found in all medical practices and will benefit most when their provider is comfortable with the issues that need to be addressed to assure the best medical and quality of life outcomes, the information herein is no longer the purview of the genetics specialist, but is relevant to many other specialists and primary care providers. We know that barriers to the integration of genomic services into these practices include lack of time, knowledge, and confidence in the skills required. Easy access to current, reliable, practical, evidence‐based information facilitates the effective transition of genomic medicine into primary care and non‐genetics specialty practice. Increasingly, families play a role in the management of what is commonly a lifelong chronic condition and, in many cases, they become more knowledgeable than their doctor. Although Management of Genetic Syndromes is not written for the public, its clear and practical presentation style, with management sections that have a system by system, checklist‐like format, allows families and providers to follow together the issues to be addressed, in the right way and at the right time. Links to consumer health information are also provided for each condition. Hopefully, as Management of Genetic Syndromes evolves to include an alternative electronic format, individual chapters will be available to families and patient advocacy groups.

Management of Genetic Syndromes remains a model for how to organize information in a meaningful format and context for physicians and families. The hype about gene discovery and effective treatment of genetic disorders persists, albeit moving closer to reality in a few circumstances. In the meantime, Management of Genetic Syndromes delivers the goods on what is really known about management and treatment of these 63 disorders. I have had the good fortune and honour to be involved in the previous three editions as both an editor and an author. The new editorial team has delivered another great edition of this must‐have book.