Which of the following is true of Kleinefelter's syndrome-

Ans. is 'a' i.e., Chromosome pattern is 47 XXY; 'b' i.e., Mental retardation is present; `c' i.e., Hypogonadism occursKLINEFELTER SYNDROME Klinefelter syndrome is the most common chromosomal disorder associated with male hypogonadism and infeility.It is defined classically by a 47, XXY karyotype with variants demonstrating additional X and Y chromosomes. (Other variants can have 48 XXXY, rarely 49 XXXXY or mosaics can be there with some cells containing normal 46, XY and others 47, XXY).o Classically, it results from meiotic non-dysjunction of sex chromosomes (40% during spermatogenesis and 60% during oogenesis). Mostly, non-dysjunction occur during 1" meiotic division.Pathophysiology:o The addition of more than 1 extra X or Y chromosome to a male karyotype results in variable physical and cognitiveabnormalities.In general, the extent of phenotypic abnormalities, including mental retardation, is related directly to the number ofsupernumerary X chromosomes.o As the number of X chromosomes increases, somatic and cognitive development are more likely to be affected.o Gonadal development is paicularly susceptible to each additional X chromosome, resulting in seminiferous tubule dysgenesis and infeility as well as hypoplastic and malformed genitalia.Moreover, mental capacity diminishes with additional X chromosomes. The intelligence quotient (IQ) is reduced by approximately 15 points for each supernumerary X chromosome.o All major areas of development, including expressive and receptive language and coordination, are affected by extra X chromosome material.Sex :Because of an additional X chromosome on an XY background, this condition is seen in males only.Age :Most males born with Klinefelter syndrome go through life without being diagnosed. Diagnosis, when made,usually occurs in adulthood. The most common indications for karyotyping are hypogonadism and infeility. PhysicalGrowtho Infants and children have normal heights, weights, and head circumferences. About 25% have clinodactyly. Height velocity is increased by age 5 years, and adult height usually is taller than average. Affected individuals also have dispropoionately long arms and legs.Some individuals with Klinefelter variant 49, XXXXY have sho stature.Central nervous systemMost 47, XXY males have normal intelligence. Family background influences IQ. Subnormal intelligence or mental retardation may be associated with the presence of a higher number of X chromosomes.o About 70% of patients have minor developmental and learning disabilities. These may include academic difficulties, delayed speech and language acquisition, diminished sho-term memory, decreased data retrieval skills, reading difficulties, dyslexia, and attention deficit disorder.o Patients may exhibit behavioral problems and psychological distress. This may be due to poor self esteem and psychosocial development or a decreased ability to deal with stress.Psychiatric disorders involving anxiety, depression, neurosis, and psychosis are seen more commonly in this group than in the general population.Sexual characteristicso Patients may lack secondary sexual characteristics because of a decrease in androgen production. This results in sparse facial/body/sexual hair, a high-pitched voice. They have eunuchoid body habitus. o By late pubey, 30-50% of boys with Klinefelter syndrome manifest gynecomastia, which is secondary to elevatedestradiol levels and increased estradiol/testosterone ratio. The risk of developing breast carcinoma is at least 20 times higher than normal.Testicular dysgenesis (small firm testis, testis size <10 mL) may be present in postpubeal patients. o Infeility/azoospermia may result from atrophy of the seminiferous tubules. Infeility is seen in practically allindividuals with a 47, XXY karyotype. Patients with Klinefelter syndrome mosaicism (46, XY/47, XXY) can be feile.o Patients may have an increased frequency of extragonadal germ cell tumors such as embryonal carcinoma, teratoma, and primary mediastinal germ cell tumor.Cardiac and circulatory problemso Mitral valve prolapse occurs in 55% of patients. o Varicose veins occur in 20-40% of patients.o The prevalence of venous ulcers is 10-20 times higher than normal, and the risk of deep vein thrombosis and pulmonary embolism is increased.Note ?o Plasma FSH and LH levels are elevated.