The diversity of Klinefelter syndrome manifestations: etiological and pathogenetic basis

Klinefelter syndrome (KS) is a genetic disorder caused by the presence of one or more extra sex X chromosomes in males. The disease has several forms, ranging from the classic 47,XXY karyotype to rarer and more severe variants such as 49,XXXXY. The most common form is the mosaic form (46,XY/47,XXY), which may be asymptomatic, and the individual is often unaware of the disorder. KS is characterized by a range of clinical manifestations, including tall stature, gynecomastia, eunuchoid body habitus, and sparse hair growth. Mental retardation is also a characteristic manifestation, and its severity correlates with the number of extra X chromosomes in the karyotype. The disease reduces quality of life and life expectancy, increasing overall morbidity and mortality rates in patients by 40%, which is due to the high risk of metabolic disorders (obesity, dyslipidemia, insulin resistance). Furthermore, patients with KS are predisposed to certain types of cancer (e.g., breast cancer), autoimmune diseases, osteoporosis, and fractures. The chromosomal abnormality itself does not affect the patient’s life expectancy. Diagnosis of the syndrome is based on cytogenetic testing. Typically, the diagnosis is established during puberty, but in severe forms, symptoms may be noticeable at earlier stages of ontogenesis. This article provides a comprehensive review of the problem, covering the epidemiology, clinical presentation, pathophysiology, laboratory diagnostic methods, drug therapy for KS, and the potential use of assisted reproductive technologies. The consequences of the disease in childhood and adulthood are analyzed in detail, with a special focus on the socio-educational aspects.