Clinical, biological and socio-professional characteristics of patients harboring the 46,XX/47,XXY mosaic sex chromosome aneuploidy: the MOSAI-XX multicenter study

Nadia Zaegel; Ingrid Plotton; Claire Morel Bouvattier; Fanny Chasseloup; Jean-Christophe Maiza; Olivier Vanakker; Peter Kamenicky; Sylvie Salenave; Tosca Lucie; Nathalie Veyt; Jacques Young; Luigi Maione

doi:10.1530/endoabs.99.P356

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Endocrine Abstracts (2024) 99 P356 | DOI: 10.1530/endoabs.99.P356

ECE2024 Poster Presentations Reproductive and Developmental Endocrinology (45 abstracts)

Clinical, biological and socio-professional characteristics of patients harboring the 46,XX/47,XXY mosaic sex chromosome aneuploidy: the MOSAI-XX multicenter study

Nadia Zaegel ^1,2 , Ingrid Plotton ³ , Morel Bouvattier Claire ^1,4 , Fanny Chasseloup ^1,4 , Jean-Christophe Maiza ⁵ , Olivier Vanakker ⁶ , Peter Kamenicky ^1,2 , Sylvie Salenave ^1,2 , Tosca Lucie ⁷ , Nathalie Veyt ⁸ , Jacques Young ^1,2 & Luigi Maione ^1,2

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Author affiliations

¹Université Paris-Saclay, Inserm UMR-S 1185, Physiologie et Physiopathologie Endocriniennes, Assistance Publique-Hôpitaux de Paris, Le Kremlin Bicetre, France; ²Service d’Endocrinologie et des Maladies de la Reproduction, Assistance Publique-Hôpitaux de Paris, Hôpital Bicêtre, Le Kremlin Bicetre, France; ³Service de médecine et de la reproduction, Hospices Civils de Lyon, Université Claude Bernard Lyon1, U1208, Lyon, France; ⁴Service d’Endocrinologie Pédiatrique, Assistance Publique-Hôpitaux de Paris, Hôpital Bicêtre, Le Kremlin Bicetre, France; ⁵Service d’Endocrinologie-Maladies Métaboliques, Chu Saint Pierre, La Reunion, France; ⁶Center for Medical Genetics Ghent University Hospital, GHENT, Belgium; ⁷Assistance Publique-Hôpitaux de Paris, Hôpital Antoine Béclère, Service d’Histologie-Embryologie-Cytogénétique, Université Paris-Saclay, Clamart, France; ⁸ASO Klinische Genetica Centrum Menselijke Erfelijkheid Leuven, Leuven, Belgium

Background: Sex chromosome mosaic aneuploidy 46,XX/47,XXy (mKS-XX) is a very rare syndrome, with only twenty-one cases previously reported. No patients’ series with mKS-XX and no comparative studies between mKS-XX and the common homogeneous Klinefelter syndrome (KS) have so far been described.

Aims: To describe the clinical, biological and socio-professional characteristics of the first series of previously unpublished patients with mKS-XX. To find predictors discriminating patients with mKS-XX from those with KS.

Patients and Methods: MOSAI-XX is a retrospective study providing descriptive analyses of consecutive patients having mKS-XX diagnosed across different European tertiary referral centers. The clinical presentation, the prevalence of disorders of sex development/ovotesticular disorder (DSD/OT), anthropometric measures, hormone levels, gonadal characteristics and socio-professional statuses (schooling, precariousness scores and job positions) of mKS-XX have been compared to those from a cohort of 121 KS patients.

Results: Fifteen patients (fourteen adults) with mKS-XX have been identified and confirmed from 1986 to 2022 from four European tertiary referral centers. The mean (±SD) percentage of XX lineage in peripheral karyotypes was 57±27% (range 7-82%). The prevalence of DSD/OT was higher in mKS-XX than in KS patients (26.7% vs 1.1%, P=0.0067). 3/30 gonads from mKS-XX and 0/242 from KS patients had an ovarian component (P=0.0012). However, the number of gonads harboring ovarian tissue was lower in our series than in pooled previous case reports (17/36, P=0.01). The final height and the statural gain over midparental height were both lower in mKS-XX than in KS patients (173.6±14.3 vs 181.3±7.9 cm, P=0.016, and -3.8±6.8 vs +7.9±7.4 cm, P=0.0003, respectively). Testicular volumes did not differ between mKS-XX and KS (2.4±0.7 vs 3.0±1.8 mL), nor did concentrations of LH, FSH, total testosterone, estradiol and testicular peptides (P=ns for all comparisons). Individuals with mKS-XX performed better in schooling achievements and more frequently occupied high intellectual professions than KS (P=0.017 and P=0.015, respectively). Precariousness scores were lower in mKS-XX than in KS patients (P=0.017).

Conclusion: We describe the first European series of patients carrying a 46,XX/47,XXy mosaic KS. We found a lower DSD/OT and a higher KS-like phenotype prevalence than those previously known from case reports. Beyond DSD/OT, we found that anthropometric measures and socio-professional statuses were also able to discriminate mKS-XX from KS. Our results improve the current knowledge about the mKS-XX syndrome. In addition, our results may have an impact on the genetic counseling for pregnant women and couples confronted with offspring carrying this rare chromosomal formula.