RT Book, Section A1 Surumpudi, Prasanth A1 Swerdloff, Ronald A2 Murray, Michael F. A2 Babyatsky, Mark W. A2 Giovanni, Monica A. A2 Alkuraya, Fowzan S. A2 Stewart, Douglas R. SR Print(0) ID 1102707004 T1 Klinefelter Syndrome and Related Sex Chromosome Aneuploidies T2 Clinical Genomics: Practical Applications in Adult Patient Care YR 2014 FD 2014 PB McGraw-Hill Education PP New York, NY SN 9780071622448 LK accessmedicine.mhmedical.com/content.aspx?aid=1102707004 RD 2024/03/29 AB Disease summary:Klinefelter syndrome is characterized by a sex chromosome aneuploidy in males. Affected males have an extra X chromosome. Males with other rare sex chromosome aneuploidy conditions have single or multiple extra X and/or Y chromosomes.Klinefelter syndrome is the most common sex chromosome abnormality with incidence of 1 in 500 live male births to 1 in 700 live male births. Often the diagnosis of Klinefelter syndrome is made after the onset of puberty.Classically, males with Klinefelter syndrome present with primary hypogonadism, small testes, azoospermia or severe oligospermia, gynecomastia, an increased arm-to-leg ratio, and learning (dyslexia) and executive skill difficulties. There is an increased risk of low bone density, cardiovascular disease, immunologic diseases, and psychiatric disorders.Signs and symptoms are influenced by several factors including how many cells have an additional X chromosome, the number of X chromosomes, X-chromosome gene inactivation on the extra X chromosome(s), and the number of CAG repeats in the androgen receptor gene.Hereditary basis:Klinefelter syndrome is a chromosomal disorder that occurs due to meiotic nondisjunction. There is a near-equal distribution of maternal and paternal meiotic nondisjunction events.Parental age may be related to an increased risk of Klinefelter syndrome.Mitotic nondisjunction can cause postfertilization and can result in individuals with mosaic forms of Klinefelter syndrome.Differential diagnosis:Klinefelter syndrome involves many systems (Table 164-1). The severity and pattern differ among patients. The differential diagnostic characteristics depend on the symptom complex of the individual patient.The differential diagnoses based on hypogonadism include other causes of primary hypogonadism, hypogonadotropic hypogonadism (eg, Kallmann syndrome), mutations in luteinizing hormone (LH) or follicle-stimulating hormone (FSH) receptor genes, microdeletions in specific regions of the Y chromosome, cryptorchidism, fragile X syndrome (see Chap. 159), defects in 3β-hydroxysteroid dehydrogenase, and 17α-hydroxylase enzymes.The differential diagnosis for learning disorders includes other causes of dyslexia. The impairment of behavioral or executive dysfunctions and behavioral disorders provide another category of diagnostic consideration (eg, ADD/ADHD).