Expansion of the phenotypic profile of the young child with XXY.

XXY is a common chromosomal abnormality which remains under diagnosed and not well understood, although it was first described more than 50 years ago. In the last ten years, with advancement in neuroimaging technology and the greater understanding of behavioral neurogenetics, there has been a resurgence of interest in children and adults with XXY. This homogenous population provides insight into the interaction between learning dysfunction, brain development and behavioral performance that may be investigated from birth onward. The unique attributes of the child from birth to 6 years of age with XXY is discussed in this paper. This paper postulates a novel reconceptualization of the phenotypic presentation of the boys with XXY. The neurodevelopmental profile of XXY is actually quite consistent over time with the common thread of speech and language deficits, motor dysfunction and frontal lobe deficits including attention, planning and organization. The early motor and speech disturbances are not random developmental delays, but rather the early presentation of the central nervous system dysfunction associated with XXY. Muscle tonus abnormalities are present in trunk, upper extremities and oral facial musculature in more than 80% of the infants with XXY.Androgen deficiency may be an integral part of the delays observed in boys with XXY, since androgen is influential in brain organization, neurobehavioral development, temperament and mood in humans. It is plausible that the earliest biomarker for androgen deficiency in XXY may be the decreased muscle tonus. Androgen deficiency may not be the only causative factor in the neurodevelopmental disturbance in individuals with XXY, but may promote a restorative function if timing and dosage is appropriate. The study of children with XXY offers an opportunity to observe the impact of the genetic and chromosomal influence on learning and behavior in a population with great homogeneity. XXY is a multifaceted spectrum disorder which demonstrates the complexity of the relationship between brain, behavior, genes and the environment.