Journal Article

Clinical but Not Histological Outcomes in Males With 45,X/46,XY Mosaicism Vary Depending on Reason for Diagnosis

Ahmed, S Faisal, Lichiardopol, Corina, Balsamo, Antonio, Maciel-Guerra, Andrea, Looijenga, Leendert H J, Cools, Martine, Guran, Tulay, Grinspon, Romina P, Ljubicic, Marie Lindhardt, Hiort, Olaf, Bertelloni, Silvano, Riedl, Stefan, Jørgensen, Anne, Cuccaro, Rieko Tadokoro, Juul, Anders, Flück, Christa E, Hannema, Sabine E, Acerini, Carlo, Holterhus, Paul Martin, Andrade, Juliana, Ortolano, Rita, Lucas-Herald, Angela K, Darendeliler, Feyza

2019

Overview

Abstract Context Larger studies on outcomes in males with 45,X/46,XY mosaicism are rare. Objective To compare health outcomes in males with 45,X/46,XY diagnosed as a result of either genital abnormalities at birth or nongenital reasons later in life. Design A retrospective, multicenter study. Setting Sixteen tertiary centers. Patients or Other Participants Sixty-three males older than 13 years with 45,X/46,XY mosaicism. Main Outcome Measures Health outcomes, such as genital phenotype, gonadal function, growth, comorbidities, fertility, and gonadal histology, including risk of neoplasia. Results Thirty-five patients were in the genital group and 28 in the nongenital. Eighty percent of all patients experienced spontaneous pubertal onset, significantly more in the nongenital group (P = 0.023). Patients were significantly shorter in the genital group with median adult heights of 156.7 cm and 164.5 cm, respectively (P = 0.016). Twenty-seven percent of patients received recombinant human GH. Forty-four patients had gonadal histology evaluated. Germ cells were detected in 42%. Neoplasia in situ was found in five patients. Twenty-five percent had focal spermatogenesis, and another 25.0% had arrested spermatogenesis. Fourteen out of 17 (82%) with semen analyses were azoospermic; three had motile sperm. Conclusion Patients diagnosed as a result of genital abnormalities have poorer health outcomes than those diagnosed as a result of nongenital reasons. Most patients, however, have relatively good endocrine gonadal function, but most are also short statured. Patients have a risk of gonadal neoplasia, and most are azoospermic, but almost one-half of patients has germ cells present histologically and up to one-quarter has focal spermatogenesis, providing hope for fertility treatment options. Clinical health outcomes in males with 45,X/46,XY mosaicism vary depending on reason for diagnosis. However, pre-neoplasia and ongoing spermatogenesis are both relatively common in all patients.

• Publisher: Endocrine Society,Copyright Oxford University Press,Oxford University Press
• Subject: Adolescent / Adult / Biopsy, Needle / Cohort Studies / Comorbidity / Fertility / Genitalia, Male - abnormalities / Germ cells / Gonadal Dysgenesis, 46,XY - epidemiology / Gonadal Dysgenesis, 46,XY - genetics / Gonads - pathology / Health aspects / Histology / Humans / Immunohistochemistry / Karyotyping / Male / Males / Mosaicism / Patients / Phenotype / Phenotypes / Quality of Life / Registries / Retrospective Studies / Semen Analysis - methods / Sex Characteristics / Sex Chromosome Aberrations / Spermatogenesis / Spermatogenesis - genetics / Turner Syndrome - epidemiology / Turner Syndrome - genetics / Young Adult