GENETICS OF TURNER SYNDROME--COGNITIVE/PHYSICAL ASPECTS

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Turner syndrome is a human genetic disorder involving females who lack all or part of one X chromosome. The principle features are short stature, infertility, and anatomic abnormalities that include webbed neck, congenital heart disease, and renal and skeletal malformations. Selected neurocognitive deficits, including impaired visual-spatial abilities, are also characteristic of Turner syndrome, but global developmental delay is uncommon. As a relatively common genetic disorder with well-defined manifestations, Turner syndrome presents the opportunity to investigate genetic factors that influence female physical and cognitive development There is potentially informative genetic and phenotypic variation among Turner syndrome subjects with partial X deletions (partial monosomy X). Careful clinical and molecular characterization of these unusual subjects who represent "experiments of nature" could link individual Turner syndrome phenotypic features to specific X chromosome regions. Similar studies are in progress for Down syndrome and other chromosome disorders. Turner syndrome is an excellent model for such phenotype mapping studies because of its prevalence, the well-characterized phenotype, and the wealth of molecular resources available for the X chromosome. The disorder is also a model for studying genetic aspects of cognition because of the selective nature of neurocognitive deficits and the relative sparing of verbal abilities. This study will examine approximately 80 partial monosomy X subjects. Each subject will have a thorough clinical evaluation and extensive neurocognitive testing to determine the presence or absence of specific Turner syndrome phenotypic features. Cell lines will be established and used for molecular studies to precisely define the subjects' X deletions. The goal of this study is to define critical regions of the X chromosome for neurocognitive deficits and physical features associated with Turner syndrome. Phenotype mapping of X deletions will be helpful for genetic counseling and for predicting which girls with Turner syndrome are at high risk for learning difficulties; these children and their parents might benefit from extra social, psychological, and educational support. The collection of cell lines will also provide a valuable resource for future studies aimed at identifying specific Turner syndrome genes. Characterization of these genes would provide insight into the pathophysiology of Turner syndrome as well as processes of normal physical and cognitive development.