Growth and Development in Children and Adolescents with Klinefelter Syndrome (47,XXY)

Abstract

Klinefelter syndrome (KS) is the most common chromosomal aberration in men. The prevalence of KS in male reproductive practices is 3–4%; however, most children and adolescents are either never diagnosed or are diagnosed late because of infertility in adulthood. KS has an effect on normal development, growth, social interactions, bone structure, and sexual and reproductive function. The aim of this chapter is to review critical aspects of growth and development in children and adolescents with KS (47,XXY) based on available literature and personal experience of authors practicing in specialized academic practice. Newborns with KS may have decreased muscle tone but in general children with KS reach developmental milestones at normal or just slightly delayed age. During early childhood boys with KS present with deficits in language and auditory processing. The depressed verbal IQ relative to overall performance of IQ is very common and should lead to karyotype prior to puberty. During puberty immaturity, insecurity, poor judgment, inappropriate assertive activities are typical. Phenotypically children with KS are indistinguishable from non-KS peers; however, during puberty simple physical exam and identification of small testes of disproportionate size to developmental stage should trigger cytogenetic evaluation. Historically young men with KS were at higher risk of autoimmune diseases, diabetes mellitus, leg ulcers, osteopenia and osteoporosis, tumors (breast and germ cells), and increased mortality in case of severe obesity, although it is now believed that morbidity associated with KS is a result of hypogonadism and hyperestrogenism in addition to abnormal function of X chromosome-linked genes. Early androgen replacement therapy, weight control, speech therapy, physical therapy, occupational therapy, and educational services have resulted in significant decrease in rate of obesity and improved both academic and socioeconomic status of young patients with KS. Early detection and appropriate management may have significant potential to improve general health, academic progress, and social integration of many boys and adolescents born with additional X chromosome. Because of high prevalence of KS and beneficial effects of early interventions, pediatricians, psychiatrists, psychologists, and neurologists should have low threshold to perform cytogenetic analysis to establish diagnosis of Klinefelter syndrome.