This set of guidelines is designed to assist pediatricians in caring for children with fragile X syndrome confirmed by DNA analysis (Table). Occasionally pediatricians are called on to advise a pregnant woman who has been informed of a prenatal diagnosis of fragile X syndrome. Therefore, guidelines are also offered for this situation.
Fragile X syndrome is usually diagnosed during childhood and is characterized by developmental delay or mental retardation, characteristic physical features, and abnormal behavioral patterns.1,2 The distinctive fragile site on the X chromosome was first described in 1969 as a discontinuous site on the long arm of the X chromosome present after cell culture under folate-deficient conditions. In 1977 the relationship of this site to X-linked mental retardation was noted, and fragile X syndrome began to be defined. Since that time, the cytogenetic, molecular, and clinical features of the condition have been more clearly defined,3 and it is now recognized as the most common hereditary cause of mental retardation. Its frequency has been estimated to be approximately per 2500 to 1 per 1250 males and 1 per 5000 to 1 per 1600 females.
The phenotype of fragile X syndrome in males often has a number of distinctive, recognizable features, including developmental delay or mental retardation, a prominent forehead, a long, thin face and a prominent jaw that appear late in childhood or early adolescence, large protuberant and slightly dysmorphic ears, and the presence of or ultimate development of macro-orchidism. This phenotype can be very subtle, is not always apparent, and becomes more identifiable with age.2
The human genes for hemophilia A and hemophilia B flank the X chromosome fragile site at Xq27.3.