Behavior and Genetics
Between approximately 1980 and 1990, major insights into the relationships between the sex chromosomes and behavior were established by interactions in the Children's Hospital IDDRC between investigators in the Genetics Program and in the Clinical/Translational Neuroscience Program. Three major groups of patients were studied, i.e., XXY and XYY males, fragile X males, XO females. The behavioral profile in XXY and XYY males was established by studies of Dr. Stanley Walzer (Department of Psychiatry) and Dr. Gerald Parks (Division of Genetics, Department of Medicine) in this IDDRC in the late 1980's (Birth Defects Original Article Series, 1990). The 47 XXY boys evidenced a continuum of language learning disability over many years. Deficits in language production and processing in the pre-school years were associated with severe and chronic reading and writing disabilities during the school years. The pattern of language deficits was relatively distinct for these boys. The temperamental style of XXY boys, also distinctive, was characterized by low activity levels, low energy content of responsiveness, high pliancy and withdrawal from novel situations and experiences. Interestingly, the boys with 47 XYY chromosomal abnormality evidenced a greater clinical diversity of communication deficits than those noted in the 47 XXY boys. Moreover, in contrast to the 47 XXY boys, the temperamental style of the 47 XYY boys was characterized by high activity level, high energy content of responsiveness, non-pliancy and distractibility. Dr. Peter Wolff and his colleagues found that mentally retarded males with the fragile site on the X chromosome exhibited a highly idiosyncratic but well coordinated stereotypic form of gaze avoidance during greeting ceremonies that involved the whole upper body (Am. J. Ment. Retard., 1989). A comparison group of persons with other etiologically defined syndromes of mental retardation did not exhibit this abnormality. Results suggested that the aberrant greeting behavior was uniquely associated with this defined genetic variety of retardation. Dr. Deborah Waber (Dev. Med. Child Neurol., 1979) studied in depth 11 patients with Turner syndrome (XO) and showed that affected patients performed less well than controls on word fluency, perception of left and right, visual-motor coordination, visual memory and motor learning.
These chromosomal-phenotypic correlations have been of particular importance in subsequent research focused on the molecular genetics of these disorders. Dr. Christopher Walsh has defined the importance of gene defects on the X-chromosome in the genesis of neuronal migration disorders (e.g., periventricular nodular heterotopia, X-linked lissencephaly/double cortex disorder).