Neurogenetic aspects in infertile men with Klinefelter syndrome

Abstract

Introduction. - Klinefelter's syndrome (SK) is characterized by the additional presence of one or more X chromosome in a male person. - Most genes from the extra X undergo inactivation, but some escape (10% of PAR1 and PAR2 ) and play a role in klinefelter pathogenesis, and could be responsible for cognitive disorders of KS patients. - The severity of the clinical features being directly proportional to the number of additional X chromosomes. (47,XXY, 48,XXXY, 49,XXXXY) !!! Purpose. - To study the neurological and cytogenetic peculiarities of KS in infertile men in order to initiate measures to improve their quality of life. Material and methods. - The study was performed on 110 men with infertility, selected during medical genetic counseling, having as selection criteria, lack of sperm in the ejaculate, elevated values of FSH and LH, the following phenotypic aspects: developmental anomalies of the external genitalia - peno-scrotal hypospadias, small testes, cryptorchidism, cranio-facial dysmorphism, waist high and disproportionate, hypogonadism, gynecomastia, mental retardation, psychosocial problems. - Karyotyping was performed on peripheral blood lymphocytes according to standard methods G-banding of metaphase chromosomes. For reporting the results, the 2016 International System of Cytogenetic Nomenclature was used. Results. - The most common chromosomal abnormality diagnosed in the 33 patients with SK was homogeneous free trisomy 47,XXY (30 cases - 90.9%), followed by the forms: mosaic (47,XXY/46,XY: 1 case), polysomy X-Y (variant 48,XXYY: 1 case - and 49,XXXXY: 1 case). 47,XXY–the classical and 47,XXY/4,XY- mosaic form - a mild to moderate mental retardation, language disorders with cognitiveverbal retardation, slow motor development, coordination disorders, immature behavior, waist high, gynecomastia, hypogonadism, azoospermia. 48,XXXY and 49,XXXXY–moderate to severe mental retardation, severe cognitive-verbal retardation, behavioral problems and lifethreatening problems were found, waist high and disproportionate, gynecomastia, developmental anomalies of the external genitalia - hypospadias, small testes, azoospermia. Conclusions. The diagnosis of the cytogenetic variant in patients with KS is of neurological importance, as the severity of the neurodevelopmental phenotype in subjects with KS is directly proportional to the number of the supernumerary X chromosome.