title: Discordant sex in monozygotic XXY/XX twins: a case report.
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.
authors.affiliation: 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.
authors.forename: G
authors.initials: G
authors.lastname: Tachon
authors.affiliation: Laboratoire de Génétique Chromosomique, Hôpital Arnaud de Villeneuve, CHRU Montpellier, Montpellier, France.
authors.forename: G
authors.initials: G
authors.lastname: Lefort
authors.affiliation: Département de Génétique Médicale, CHRU Montpellier, Faculté de Médecine Université Montpellier 1, Montpellier, France.
authors.forename: J
authors.initials: J
authors.lastname: Puechberty
authors.affiliation: Laboratoire de Génétique Chromosomique, Hôpital Arnaud de Villeneuve, CHRU Montpellier, Montpellier, France.
authors.forename: A
authors.initials: A
authors.lastname: Schneider
authors.affiliation: Endocrinologie Pédiatrique, Hôpital Lapeyronie, CHRU Montpellier, Montpellier, France.
authors.forename: C
authors.initials: C
authors.lastname: Jeandel
authors.affiliation: Service de Gynécologie Obstétrique, Hôpital Arnaud de Villeneuve, CHRU Montpellier, Montpellier, France.
authors.forename: P
authors.initials: P
authors.lastname: Boulot
authors.affiliation: Service de Radiopédiatrie, Hôpital Arnaud de Villeneuve, CHRU Montpellier, Montpellier, France.
authors.forename: O
authors.initials: O
authors.lastname: Prodhomme
authors.affiliation: Service de Neuropédiatrie, Hôpital Gui-de-Chauliac, CHRU Montpellier, INSERM U1046, Université Montpellier 1-2, Montpellier, France.
authors.forename: P
authors.initials: P
authors.lastname: Meyer
authors.affiliation: Laboratoire de Génétique Chromosomique, Hôpital Arnaud de Villeneuve, CHRU Montpellier, Montpellier, France.
authors.forename: S
authors.initials: S
authors.lastname: Taviaux
authors.affiliation: Unité Médicale des Maladies Auto-inflammatoire, Hôpital Arnaud de Villeneuve, CHRU Montpellier, Montpellier, France.
authors.forename: I
authors.initials: I
authors.lastname: Touitou
authors.affiliation: Laboratoire de Génétique Chromosomique, Hôpital Arnaud de Villeneuve, CHRU Montpellier, Montpellier, France.
authors.forename: F
authors.initials: F
authors.lastname: Pellestor
authors.affiliation: Département de Génétique Médicale, CHRU Montpellier, Faculté de Médecine Université Montpellier 1, Montpellier, France d-genevieve@chu-montpellier.fr.
authors.forename: D
authors.initials: D
authors.lastname: Geneviève
authors.affiliation: Laboratoire de Génétique Chromosomique, Hôpital Arnaud de Villeneuve, CHRU Montpellier, Montpellier, France.
authors.forename: V
authors.initials: V
authors.lastname: Gatinois
mesh_terms: D002675:Child, Preschool; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations; D005260:Female; D006062:Gonadotropins / Q000097:blood; D006801:Humans; D059785:Karyotype; D007713:Klinefelter Syndrome / Q000235:genetics*; D008297:Male; D009030:Mosaicism / Q000196:embryology*; D010641:Phenotype; D013739:Testosterone / Q000097:blood; D038522:Twinning, Monozygotic / Q000235:genetics*; D014427:Twins / Q000235:genetics
chemical_list: D006062:Gonadotropins; D013739:Testosterone
keywords: Klinefelter; monozygotic; mosaicism; sex discordance; twin