Fragile X Syndrome: Diagnosis, Treatment, And Research

man cytogenetics isn't as significant as the discovery of flight\p=m-\oris it? Cytogenetics is a major part of the foundation for our understanding ofmany aspects of clinicalmedicine, molecular genetics, and the Human Genome Project. In the fall of 1997, the American Medical Association is planning amajor conference on genetic medicine because fewer than one in 10 physicians have confidence in their ability to provide genetic counseling. Fragile X syndrome (FXS) is just one of several X-linked mental retardation (XLMR) syndromes. The finding of a cytogenetic abnormality in an XLMR syndrome and thus the syndrome's name, occurred in 1969. My career in cytogenetics began in 1974. Thus, except for the first 5 years of its existence, I've observed the evolution of knowl¬ edge about FXS. The prevalence of XLMR is from one in 500 to one in 1800 males, and it is further estimated that one third of XLMR is from FXS. Given this prevalence and heritable nature of these disorders, it seems that clinicians should be knowledgeable onXLMR from clinical and liability standpoints. This second edition of Fragile X Syn¬ drome is most valuable to primary care physicians, family practitioners, pediatricians, and internists. The first chapter provides an excellent clinical spectrum of FXS with attention to physical and behavioral phenotypes. It also addresses these features in females with FXS. Few clinicians realize that FXS involves all the other body systems and is not just a mental retardation disorder. Internists and family practitioners need to under¬ stand the endocrine, neurologic, and car¬ diac manifestations of FXS for diagno¬ sis, genetic counseling, and clinical management. Pediatricians should be aware that many FXS children were pre¬ viously diagnosed with attention deficit hyperactivity disorder, autism, nonspe¬ cific mental retardation, pervasive de¬ velopment disorder, learning disability, or emotional impairment. Obstetricians and family practitioners should realize that women with the FXS premutation are at risk for premature ovarian failure. This is important for coun¬ seling, clinical management, and family planning. Pharmacotherapy ofthe 15% to 20% of FXS males with seizures is chal¬ lenging when one considers all the other clinical issues of FXS patients. Diagnosis of FXS is expensive. Cur¬ rent guidelines are that any child or adult who presents with autism, autistic fea¬ tures, or mental retardation without a specific cause should undergo DNA test¬ ing for FXS and cytogenetic testing for other chromosomal structural abnormali¬ ties. These tests cost about $1000. Inman¬ aged care, especiallywith capitated plans, physicians need to determine carefully which patients need testing. The second edition of Fragile X Syn¬ drome includes updated chapters on the ' cytogenetic and molecular biology of the FXS mutation and premutation. The first half addresses the diagnosis and research aspects and is well referenced. The latter half is dedicated to treatment and intervention. The chapter that em¬ phasizes an integrated approach to in¬ tervention could easily qualify for continuing medical education credit. Much of the book, especially these latter chap¬ ters, outlines a step-by-step, even hands-