Klinefelter Syndrome XXY/XYY

Chromosomal disorder characterized by supernumerary X chromosome(s) in male subjects associated with infertility and hypogonadism.

47-XXY Syndrome; Hypogonadotropic Hypogonadism; Klinefelter-Reifenstein Syndrome; Klinefelter-Reifenstein-Albright Syndrome; Seminiferous Tubule Dysgenesis; Xq Klinefelter Syndrome.

First described in 1942 by the American physicians H.F. Klinefelter, Jr., E.C. Reifenstein, Jr., and F. Albright.

Chromosomal disorder affecting only males. Estimated prevalence of 1:600-700 in the male population. No racial predilection. This disorder is the most common chromosomal cause of male hypogonadism and infertility.

Nondisjunction of sex chromosomes during maternal meiosis (53%) or paternal meiosis (47%) results in 47,XXY genotype classically, although variants such as XXYY, XXXY, and XXXXY, and mosaic patterns, such as XXX/XY, also exist.

Additional X chromosome(s) result in cognitive abnormalities and affect the development of secondary sexual characteristics (proportionally to the extra number of X chromosomes). Extra sex chromosomes usually result from an error of nondisjunction during parental gametogenesis. The primary testicular failure causes elevation of gonadotropin levels because of a lack of feedback inhibition on the pituitary gland. In addition to androgen deficiency, which causes eunuchoid body proportions with gynecomastia, there is an increased incidence of autoimmune disorders (e.g., systemic lupus erythematosus, rheumatoid arthritis).

Clinical characteristics and genotyping.

Phenotypically male. Physical manifestations of this syndrome develop at puberty. Typically small, soft testes with underdeveloped secondary sex characteristics, such as sparse facial and body hair. Affected men are infertile as a consequence of azoospermia caused by sclerosed seminiferous tubules. Patients may be tall with long limbs. Osteoporosis may lead to vertebral collapse and even scoliosis. Unless treated with exogenous testosterone starting at puberty, patients can become obese and develop diabetes mellitus. A recent study from Britain showed that these patients have a reduced life expectancy. The main reasons were peripheral vascular disease, pulmonary embolism, diabetes mellitus (secondary to insulin resistance), respiratory disease (restrictive pneumopathy), and nervous system disease (e.g., subarachnoid hemorrhage, epilepsy). Mortality from ischemic heart disease, however, was reduced.

Evaluate and optimize control of diabetes mellitus if necessary. Assess for long-term complications of diabetes (atherosclerosis, renal disease). Vertebral body fractures can result in decreased mobility of spine and/or compression of nerves or spinal cord. Any neurologic abnormalities should be documented preoperatively. Cervical spine mobility should be evaluated. Patient cooperation may be limited if mental retardation is present and sedative/anxiolytic premedication and/or the presence of the primary caregiver for induction of anesthesia may be helpful.

Perioperative control of blood glucose levels to prevent hypoglycemia or severe hyperglycemia. Difficult intubation if cervical spine mobility is limited. Consider awake intubation or avoid airway manipulation altogether if there is risk of neurologic injury with movement of the cervical spine. Central neuraxial anesthesia techniques are controversial if spinal problems are present and if in doubt should best be avoided. Scoliosis makes proper positioning more difficult.

No specific implications.

Fragile X Syndrome: Mental retardation, joint hyperlaxity, attention deficit, unstable mood, autistic-like behavior, epilepsy in 25% of patients. Boys are more severely affected than girls. Caused by a mutation on the FMR1 gene, which is located on the long arm of the X chromosome.

Hypogonadism in Males: Features of eunuchoidism (sparse body hair, underdevelopment of skeletal muscles, delayed epiphyseal closure resulting in long arms and legs) caused by interruption of the hypothalamic-pituitary-gonadal axis, which can be genetic (Kallmann syndrome, congenital adrenal hypoplasia, several gene mutations) or secondary to other disorders (particularly brain tumors).