Women at 40 years have a four times higher risk for a child with Klinefelter syndrome than women aged 24 years.The extra chromosome is retained because of a nondisjunction event during paternal meiosis I, maternal meiosis I, or maternal meiosis II (gametogenesis). The relevant nondisjunction in meiosis I occurs when homologous chromosomes, in this case the X and Y or two X sex chromosomes, fail to separate, producing a sperm with an X and a Y chromosome or an egg with two X chromosomes. Fertilizing a normal (X) egg with this sperm produces an XXY offspring (Klinefelter). Fertilizing a double X egg with a normal sperm also produces an XXY offspring (Klinefelter).Another mechanism for retaining the extra chromosome is through a nondisjunction event during meiosis II in the egg. Nondisjunction occurs when sister chromatids on the sex chromosome, in this case an X and an X, fail to separate. An XX egg is produced, which when fertilized with a Y sperm, yields an XXY offspring. This XXY chromosome arrangement is one of the most common genetic variations from the XY karyotype, occurring in about one in 500 live male births. See also Triple X syndrome. In mammals with more than one X chromosome, the genes on all but one X chromosome are not expressed; this is known as X inactivation. This happens in XXY males, as well as normal XX females.
In 2018, the American College of Chest Physician stated that it is presents if there is an inadequate response to high-dose vasopressor therapy defined as ≥ 0.5 mg/kg/min norepinephrine-equivalent dose. Management
Reversing the underlying causes of vasodilatory shock, stabilizing hemodynamic, preventing renal, myocardial, and other organs from injuries due to hypoperfusion and hypoxia, and taking necessary measures to safeguard against complications including venous thromboembolism are served as the top priorities during the treatment.The initial treatment aiming at restoring effective blood pressure in patients that have refractory shock typically starts with introducing norepinephrine and dopamine. Vasopressin comes as the second-line agent.However, high-dose therapy is linked to excessive coronary, splanchnic vasoconstriction, and hypercoagulation. Excessive vasoconstriction can cause cardiac output reduction or even fatal heart complication particularly in those with weak myocardial function.In those whose vasodilatory shock is caused by hypocalcemic cardiomyopathy in the context of dilated cardiomyopathy with documented both reduced heart ejection fraction and contractile performance, the uses of calcium and active vitamin D or recombinant human parathyroid hormone treatment are viable since there were many successful cases reported while given the physiological role of calcium on muscle contraction.A successful treatment requires leveraging the respective unique contributions of a multi-disciplinary team not only critical care doctors and often, infectious disease specialists but also respiratory therapy, nursing, pharmacy and others in collaboration. Epidemiology
Observational studies suggest that, about 6% to 7% of critically ill people may end up developing refractory shock. Prognosis
Early recognition and rapid treatment initiation are crucial to saving life.