Book Review

Genetic Disorders of Human Sexual Development

N Engl J Med 2000; 342:362-363February 3, 2000

Article

Genetic Disorders of Human Sexual Development
By Leonard Pinsky, Robert P. Erickson, and R. Neil Schimke. 410 pp., illustrated. New York, Oxford University Press, 1999. $85. ISBN: 0-29-510907-4

An understanding of the genetic problems underlying aberrant sexual development has been one of the notable advances in developmental medicine. The authors of Genetic Disorders of Human Sexual Development recognized the need for an update on the achievements in this area and have provided a very good synopsis. The three authors are a perfect team, since they are recognized experts in pediatrics and genetics.

The book has 5 parts, encompassing 21 chapters. There is a good index and an extremely useful appendix of differential diagnoses for the most common features of various genital–sexual disorders. The first part of the book describes normal gonadal development and sexual differentiation, with an emphasis on the key genes involved in sex determination. This introduction is an excellent orientation to recent developments in the field. There is also a concise review of the functional (biochemical and endocrinologic) aspects of gonadal development and sexual differentiation. The authors underline the plasticity and vulnerability of sex determination (especially in males), which can be influenced by various genetic and environmental factors.

The second part, entitled “Clinical Approach,” the shortest in the book, consists of only one chapter. This chapter is very important, however, because it covers ethical issues and problems concerning early diagnosis, assignment of sex, management options, and counseling.

The main parts of the book, on gonadal maldevelopment and sexual maldevelopment, constitute a detailed catalogue of disorders. The catalogue is logically organized; all the disorders are listed either according to the mapping of an aberration to a sex chromosome or an autosome or according to a distinct functional feature, such as sex hormone sensitivity or excess gonadotropin. For most of the common disorders, separate sections cover clinical, imaging, and laboratory features, genotyping and gene expression, and management, with a section of discussion and speculation. We enjoyed reading the discussion-and-speculation sections, which are well written and contain the authors' thoughts and experiences.

The book also provides a long list of rare syndromes and nonsyndromal disorders that involve genital and sexual abnormalities. The list is user-friendly, with the relevant references listed directly underneath each disorder. The authors provide good, up-to-date references that contain full titles, and they cite original articles rather than textbooks. The only flaw in the general organization of the book is the relative scarcity of illustrations. For a clinician attempting to diagnose a case with special features — facial anomalies, for example — a photograph would have been more helpful than a description.

The last part of the book covers genetic forms of gamete failure, including obstructive azoospermia in cystic fibrosis and meiotic abnormalities. The accompanying table of murine genes known to be involved in male sterility provides a good list of candidate genes to investigate in men with infertility. Very little is known about the genetic aspects of impaired spermatogenesis in humans.

In general, this book is well written, up to date, thorough, and logically organized. It could become the definitive textbook on genetic disorders of human sexual development. However, there is one important omission. There is no section on germ-cell tumors or their preinvasive precursors, carcinoma in situ and gonadoblastoma — diseases associated with a number of disorders of gonadal and sexual development. These tumors are not even listed in the index. Gonadal malignancy of germ cells is only marginally mentioned, in the chapter on clinical approaches, as a potential problem in the management of gonadal dysgenesis and cryptorchidism, although testicular tumors derived from Leydig or Sertoli cells, which are much less common than germ-cell tumors, are mentioned as being associated with the Peutz–Jeghers syndrome and the Carney complex. Despite this omission, this book is a valuable reference that should interest every pediatrician, endocrinologist, urologist, andrologist, gynecologist, and geneticist who deals with disorders of the reproductive system.

Ewa Rajpert-De Meyts, M.D., Ph.D.
Niels E. Skakkebaek, M.D., D.M.Sc.
Copenhagen University Hospital, DK-2100 Copenhagen, Denmark