prenatal diagnosis of a double trisomy 48, xxy, +13: klinefelter and patau syndromes

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  • American Journal of Medical Genetics 132A:342 (2005)

    CorrespondencePrenatal Diagnosis of a Double Trisomy 48, XXY, 13:Klinefelter and Patau Syndromes

    To the Editor:

    As a reply to research letter: Double trisomy, by Shiboet al. [2004], we report on the prenatal diagnosis of a doubleaneuploidy involving chromosome X and chromosome 13, in awomen who was referred for CVS. To our knowledge, this isthe first report describing a prenatal diagnosis of Klinefelterand Patau syndromes. Prenatal diagnosis of simultaneousoccurrence of double trisomy is extremely rare.

    Cytogenetic data on products of conception from sponta-neous abortions studied over a 10-year period have beenreviewed for double trisomy by Reddy [1997]. A total of 3,034spontaneous abortions were karyotyped between 1986 and1997. Twenty-two cases with double trisomy were found.

    Here, we describe the first prenatally detected case of adouble trisomy involving chromosome 13 and the sex chromo-somes (48, XXY,13) (Klinefelter/Patau syndrome) in a 39-year-old female who was referred for CVS at 11 weeks ofgestation. Ultrasonorographic examination showed nuchaltranslucency. Chromosome analysis of both direct (cytotro-phoblast) and long-term (extra embryonic) cultures, showedan abnormal 48, XXY, 13 in all examined metaphases(10 metaphases from direct and 10 from long-term culture).Both parents had a normal karyotype. The patient electedto terminate the pregnancy at 14 weeks of gestation. Post-termination tissue sample investigations and skin biopsyof the aborted fetus confirmed the karyotype. Unfortunately,the parents were not seen after the abortion, so, it was notpossible to determine the possible origin of the two abnormal-ities by molecular comparison of the fetal and parentalgenotypes.

    Although non-disjunction is the most common cause ofchromosome abnormalities, the presence of two numericalabnormalities in a single conceptus is rarely observed. Froma careful review of the literature, only a few cases of doubletrisomy have been reported so far. Recently, a prenataldiagnosis of double trisomy 48, XXX, 18 has been describedby Chen et al. [2000] in one case of Klinefelter/Edwardssyndrome. Another patient of 48, XXY,18 has been presentedas a poster during the Third European Cytogenetics Con-ference by Tunca et al. [2001]. A prenatally detected case of 48,XXX, 21 has been reported by Park et al. [1995]. Shibo et al.[2004] indicated that no report of 48, XXX, 13 and 48,XXY,13 is known. Here, we report on the first prenatally detectedcase of Klinefelter and Patau syndromes (48, XXY, 13).

    The mechanisms by which double aneuploidies arise havenot been well studied. Robinson et al. [2001] report cytogeneticand molecular findings from 122 spontaneous abortions anddemonstrate that the only double trisomy found was theconsequence of both a maternal and a paternal meiotic error.We think that various mechanisms may be considered bywhich they might arise. All require a minimum of two errorsin cell division. Random non-disjunction in both gametescould lead to the formation of a doubly aneuploid zygote.Alternatively, a single global defect might cause multiple non-disjunctions in the formation of a single gamete. Study ofadditional examples of multiple aneuploidy are needed todetermine the nature of the errors in such cases.


    Chen CP, Chern SR, Yeh LF, Chen WL, Chen LF, Wang W. 2000. Prenataldiagnosis and genetic analysis of double trisomy 48, XXX, 18. PrenatDiagn 20:750753.

    Park VM, Bravo RR, Shulman LP. 1995. Double non-disjunction in maternalmeiosis II giving rise to a fetus with 48, XXX,21. J Med Genet 32:650653.

    Reddy KS. 1997. Double trisomy in spontaneous abortions. Hum Genet101:339345.

    Robinson WP, Mc Fadden DE, Stephenson MD. 2001. The origin ofabnormalities in recurrent aneuploidy/polyploidy. Am J Hum Genet69:12451254.

    Shibo L, Hassed S, Mulvihill J, Nair A, Hopcus D. 2004. Double trisomy. AmJ Med Genet 124A:9698.

    Tunca Y, Ergun A, Soysal Y, Sefali M, Imirzalioglu N. 2001. The roleof prenatally diagnosed bilateral choroids plexus cysts in doubletrisomy (Klinefelter/Edwards syndrome). Annales de Genetique,Third European Cytogenetics Conference, Paris, July 710, Poster no.3, 515 s 140.

    Rossano RossinoDepartimento di ScienzeBiomediche e BiotechnologieUniversita di CagliariCagliari, Italy

    Anna Lisa Nucaro*Istituto di Neurogenetica e

    NeurofarmacologiaCNR, Cagliari, Italy

    *Correspondence to: Anna Lisa Nucaro, Istituto di Neurogen-etica e Neurofarmacologia del CNR, Via Boccaccio 8, 09047Selargius, Cagliari, Italy. E-mail:

    Received 24 March 2004; Accepted 20 September 2004

    DOI 10.1002/ajmg.a.30477

    2004 Wiley-Liss, Inc.