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Hum Reprod. 2014 Dec;29(12):2814-20. doi: 10.1093/humrep/deu275. Epub 2014 Oct 21.

Discordant sex in monozygotic XXY/XX twins: a case report.

Author information

1
Département de Génétique Médicale, CHRU Montpellier, Faculté de Médecine Université Montpellier 1, Montpellier, France Laboratoire de Génétique Chromosomique, Hôpital Arnaud de Villeneuve, CHRU Montpellier, Montpellier, France.
2
Laboratoire de Génétique Chromosomique, Hôpital Arnaud de Villeneuve, CHRU Montpellier, Montpellier, France.
3
Département de Génétique Médicale, CHRU Montpellier, Faculté de Médecine Université Montpellier 1, Montpellier, France.
4
Endocrinologie Pédiatrique, Hôpital Lapeyronie, CHRU Montpellier, Montpellier, France.
5
Service de Gynécologie Obstétrique, Hôpital Arnaud de Villeneuve, CHRU Montpellier, Montpellier, France.
6
Service de Radiopédiatrie, Hôpital Arnaud de Villeneuve, CHRU Montpellier, Montpellier, France.
7
Service de Neuropédiatrie, Hôpital Gui-de-Chauliac, CHRU Montpellier, INSERM U1046, Université Montpellier 1-2, Montpellier, France.
8
Unité Médicale des Maladies Auto-inflammatoire, Hôpital Arnaud de Villeneuve, CHRU Montpellier, Montpellier, France.
9
Département de Génétique Médicale, CHRU Montpellier, Faculté de Médecine Université Montpellier 1, Montpellier, France d-genevieve@chu-montpellier.fr.

Abstract

We report a case of discordant phenotypic sex in monozygotic twins mosaic 47,XXY/46,XX: monozygotic heterokaryotypic twins. The twins presented with cognitive and comprehension delay, behavioural and language disorders, all symptoms frequently reported in Klinefelter syndrome. Molecular zygosity analysis with several markers confirmed that the twins are in effect monozygotic (MZ). Array comparative genomic hybridization found no evidence for the implication of copy number variation in the phenotypes. Ultrasound scans of the reproductive organs revealed no abnormalities. Endocrine tests showed a low testosterone level in Twin 1 (male phenotype) and a low gonadotrophin level in Twin 2 (female phenotype) which, combined with the results from ultrasound examination, provided useful information for potentially predicting the future fertility potential of the twins. Blood karyotypes revealed the presence of a normal 46,XX cell line and an aneuploïd 47,XXY cell line in both patients. Examination of the chromosome constitutions of various tissues such as blood, buccal smear and urinary sediment not surprisingly showed different proportions for the 46,XX and 47,XXY cell lines, which most likely explains the discordant phenotypic sex and mild Klinefelter features. The most plausible underlying biological mechanism is a post-zygotic loss of the Y chromosome in an initially 47,XXY zygote. This would result in an embryo with both 46,XX and 47,XXY cells lines which could subsequently divide into two monozygotic embryos through a twinning process. The two cell lines would then be distributed differently between tissues which could result in phenotypic discordances in the twins. These observations emphasize the importance of regular paediatric evaluations to determine the optimal timing for fertility preservation measures and to detect new Klinefelter features which could appear throughout childhood in the two subjects.

KEYWORDS:

Klinefelter; monozygotic; mosaicism; sex discordance; twin

PMID:
25336706
DOI:
10.1093/humrep/deu275
[Indexed for MEDLINE]

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