Objective High-grade aneuploidies of X and Y sex chromosomes (HGAs) are exceedingly rare and complex conditions. We aimed to investigate the effect of supernumerary X chromosomes (extra-Xs) on the clinical, hormonal, metabolic, and echocardiographic features of patients with HGAs. Design and Methods In a cross-sectional study, we compared 23 subjects with HGAs and 46 age-matched subjects with 47,XXY Klinefelter syndrome (KS), according to the number of extra-Xs: two (47,XXY and 48,XXYY), three (48,XXXY and 49,XXXYY), or four supernumerary Xs (49,XXXXY). A second cohort consisting of 46 pubertal stage-matched KS subjects was employed for validation. Clinical, hormonal, metabolic and ultrasonographic parameters were collected and analyzed. Results The increase in the number of extra-Xs was associated with a progressive adverse effect on height, pubertal development, testicular volume and function, adrenal steroidogenesis, and thyroid function. A progressive linear increase in ACTH and a decrease in cortisol/ACTH ratios were found. Weight and body mass index, Sertoli cell function, lipid profile, and glucose tolerance post-oral glucose tolerance test were all worse in the HGA cohort compared to KS. Cardiac evaluation revealed a linear association with reduced left and right end-diastolic diameters and reduced ejection fraction. Conclusion The increase in the number of extra-Xs is associated with a “dose-dependent” progressive impairment in steroid producing glands, thyroid function, cardiac structure, and performance.

From Klinefelter Syndrome to High Grade Aneuploidies: Expanding the Gene-dosage Effect of Supernumerary X Chromosomes / Spaziani, Matteo; Carlomagno, Francesco; Tarantino, Chiara; Angelini, Francesco; Paparella, Roberto; Tarani, Luigi; Putotto, Carolina; Badagliacca, Roberto; Pozza, Carlotta; Isidori, Andrea; Gianfrilli, Daniele. - In: THE JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM. - ISSN 1945-7197. - (2024). [10.1210/clinem/dgad730]

From Klinefelter Syndrome to High Grade Aneuploidies: Expanding the Gene-dosage Effect of Supernumerary X Chromosomes

Matteo Spaziani;Francesco Carlomagno;Chiara Tarantino;Francesco Angelini;Roberto Paparella;Luigi Tarani;Carolina Putotto;Roberto Badagliacca;Carlotta Pozza;Andrea M Isidori;Daniele Gianfrilli
2024

Abstract

Objective High-grade aneuploidies of X and Y sex chromosomes (HGAs) are exceedingly rare and complex conditions. We aimed to investigate the effect of supernumerary X chromosomes (extra-Xs) on the clinical, hormonal, metabolic, and echocardiographic features of patients with HGAs. Design and Methods In a cross-sectional study, we compared 23 subjects with HGAs and 46 age-matched subjects with 47,XXY Klinefelter syndrome (KS), according to the number of extra-Xs: two (47,XXY and 48,XXYY), three (48,XXXY and 49,XXXYY), or four supernumerary Xs (49,XXXXY). A second cohort consisting of 46 pubertal stage-matched KS subjects was employed for validation. Clinical, hormonal, metabolic and ultrasonographic parameters were collected and analyzed. Results The increase in the number of extra-Xs was associated with a progressive adverse effect on height, pubertal development, testicular volume and function, adrenal steroidogenesis, and thyroid function. A progressive linear increase in ACTH and a decrease in cortisol/ACTH ratios were found. Weight and body mass index, Sertoli cell function, lipid profile, and glucose tolerance post-oral glucose tolerance test were all worse in the HGA cohort compared to KS. Cardiac evaluation revealed a linear association with reduced left and right end-diastolic diameters and reduced ejection fraction. Conclusion The increase in the number of extra-Xs is associated with a “dose-dependent” progressive impairment in steroid producing glands, thyroid function, cardiac structure, and performance.
2024
sex chromosomes, aneuploidy, HGA, Klinefelter syndrome, X chromosome, 47,XXY, 48,XXXY, 48,XXYY, 49,XXXXY, 49,XXXYY
01 Pubblicazione su rivista::01a Articolo in rivista
From Klinefelter Syndrome to High Grade Aneuploidies: Expanding the Gene-dosage Effect of Supernumerary X Chromosomes / Spaziani, Matteo; Carlomagno, Francesco; Tarantino, Chiara; Angelini, Francesco; Paparella, Roberto; Tarani, Luigi; Putotto, Carolina; Badagliacca, Roberto; Pozza, Carlotta; Isidori, Andrea; Gianfrilli, Daniele. - In: THE JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM. - ISSN 1945-7197. - (2024). [10.1210/clinem/dgad730]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1706833
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