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
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
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
No specific implications.