CLINICAL REPORT
Sex-Discordant Monochorionic Twins with Blood and Tissue Chimerism David Rodriguez-Buritica,1,2* Kitiwan Rojnueangnit,3,2 Ludwine M. Messiaen,2 Fady M. Mikhail,2 and Nathaniel H. Robin2 1
Division of Genetics, Department of Pediatrics, School of Medicine University of Texas at Houston, Houston, Texas
2
Department of Genetics, University of Alabama at Birmingham, Birmingham, Alabama Department of Pediatrics, Faculty of Medicine, Thammasat University, Bangkok, Thailand
3
Manuscript Received: 12 October 2014; Manuscript Accepted: 2 February 2015
We report on a pair of normally conceived monochorionic/dizygotic (MC/DZ) sex discordant twins. The comparison of blood and skin genotypes revealed that the chimerism was also present in the skin. We conjecture about the developmental origins of this case.
How to Cite this Article: Rodriguez-Buritica D, Rojnueangnit K, Messiaen LM, Mikhail FM, Robin NH. 2015. Sex-discordant monochorionic twins with blood and tissue chimerism.
Ó 2015 Wiley Periodicals, Inc.
Key words: monochorionic/dizygotic twin pregnancy; chimer-
Am J Med Genet Part A 167A:872–877.
ism; twin–twin transfusion syndrome; spontaneously conceived MC/DZ twins
CLINICAL REPORT INTRODUCTION Monochorionic (MC) twins are expected to be genetically and phenotypically identical since they arise during the early cleavage of a single embryo. This notion was challenged by reports of sexdiscordant MC/DZ twins, demonstrating that dizygotic twins (DZ) can also be monochorionic [Quintero et al., 2003; Souter et al., 2003; Williams et al., 2004; Ginsberg et al., 2005; Aoki et al., 2006; Souter et al., 2007; Walker et al., 2007; Ekelund et al., 2008; Hackmon et al., 2009; Hawcutt et al., 2011; Chen et al., 2013; Kanda et al., 2013]. This finding provided an explanation for the observed discordant phenotype seen in some cases of MC twins [Bourthoumieu et al., 2006; Charles, 2006; Malan et al., 2006] Despite their separate origin, MC/DZ twins may demonstrate mixed blood genotypes, with the genotype from each twin represented in each twin’s circulation, and may be discordant for their phenotype. This is due to confluent placental circulation [Bourthoumieu et al., 2006]. This has been referred to as “confined-blood chimerism.” This is relatively common compared to solid tissue chimerism, which to our knowledge, has only been demonstrated in two reports [Ginsberg et al., 2005; Souter et al., 2007]. Most of the reported cases are associated with the use of assisted reproductive technology (ART), but this might represent ascertainment bias [Quintero et al., 2003; Souter et al., 2003; Williams et al., 2004; Ginsberg et al., 2005; Aoki et al., 2006; Souter et al., 2007; Walker et al., 2007; Ekelund et al., 2008; Hawcutt et al., 2011; Chen et al., 2013; Kanda et al., 2013]. We present a case of normally conceived sex-discordant MC/DZ twins, with identical blood karyotype but chimeric skin genotype in one of the twins, which suggest an atypical mechanism of twinning.
Ó 2015 Wiley Periodicals, Inc.
Twin A is a male who was evaluated at age 2 months for aortic stenosis and hypospadias. A blood karyotype showed two cell lines (46,XY/46,XX). This prompted us to evaluate twin B, a phenotypically normal girl who also had two blood cell lines (46,XX/46,XY). Both twins were evaluated using blood karyotype, array comparative genomic hybridization with single nucleotide polymorphisms (aCGHþSNP), interphase FISH X/Y, skin karyotype, and blood and buccal microsatellite analyses. Supplemental analysis included the male’s skin microsatellites, parental microsatellites and molecular testing for single gene sex-reversal and hormonal studies.
Prenatal History The patients were born to a 21-year-old mother G4P4A1 after natural conception. Prenatal course was uncomplicated with no prenatal exposures. The twins were born by cesarian at 39 weeks of gestation. Prenatal ultrasound study revealed the presence of a single placenta but no evidence of twin–twin transfusion. Birth weights were 2.3 kg for the boy and 2.1 kg for the girl. Macroscopic and microscopic placental pathology revealed a monochorionic/ diamniotic pregnancy.
Correspondence to: David Rodriguez-Buritica, M.D., 431 Fannin Street, MSB 3.144, Houston, Texas 77030. E-mail: [email protected] Article first published online in Wiley Online Library (wileyonlinelibrary.com): 23 February 2015 DOI 10.1002/ajmg.a.37022
872
RODRIGUEZ-BURITICA ET AL.
873
TABLE I. Results of Cytogenetic and Endocrine Studies of the Twins TEST Blood karyotype Skin karyotype Blood interphase FISH X/Y analysis Blood aCGHþSNP array
SRY DHH DAX1 LH (mIU/ml) FSH (mIU/ml) Testosterone (ng/dl) Estradiol (pg/ml) AMH (ng/dl)
Male twin(A) at 2 months 46,XY [14]/46,XX [16]
Male twin(A) at 11 months 46,XY [18]/46,XX [12]
XY in 86/200 cells (43%) XX in 114/200 cells (57%)
Female twin (B) at 3 months 46,XX [9]/46,XY [21] 46, XX [32] XX in 89/200 cells (44.5%) XY in 111/200 cells (55.5%)
Female twin (B) at 10 months XX in 79/200 cells (39.5%) XY in 121/200 cells (60.5%)
Sex-Discordant Monochorionic Twins with Blood and Tissue Chimerism David Rodriguez-Buritica,1,2* Kitiwan Rojnueangnit,3,2 Ludwine M. Messiaen,2 Fady M. Mikhail,2 and Nathaniel H. Robin2 1
Division of Genetics, Department of Pediatrics, School of Medicine University of Texas at Houston, Houston, Texas
2
Department of Genetics, University of Alabama at Birmingham, Birmingham, Alabama Department of Pediatrics, Faculty of Medicine, Thammasat University, Bangkok, Thailand
3
Manuscript Received: 12 October 2014; Manuscript Accepted: 2 February 2015
We report on a pair of normally conceived monochorionic/dizygotic (MC/DZ) sex discordant twins. The comparison of blood and skin genotypes revealed that the chimerism was also present in the skin. We conjecture about the developmental origins of this case.
How to Cite this Article: Rodriguez-Buritica D, Rojnueangnit K, Messiaen LM, Mikhail FM, Robin NH. 2015. Sex-discordant monochorionic twins with blood and tissue chimerism.
Ó 2015 Wiley Periodicals, Inc.
Key words: monochorionic/dizygotic twin pregnancy; chimer-
Am J Med Genet Part A 167A:872–877.
ism; twin–twin transfusion syndrome; spontaneously conceived MC/DZ twins
CLINICAL REPORT INTRODUCTION Monochorionic (MC) twins are expected to be genetically and phenotypically identical since they arise during the early cleavage of a single embryo. This notion was challenged by reports of sexdiscordant MC/DZ twins, demonstrating that dizygotic twins (DZ) can also be monochorionic [Quintero et al., 2003; Souter et al., 2003; Williams et al., 2004; Ginsberg et al., 2005; Aoki et al., 2006; Souter et al., 2007; Walker et al., 2007; Ekelund et al., 2008; Hackmon et al., 2009; Hawcutt et al., 2011; Chen et al., 2013; Kanda et al., 2013]. This finding provided an explanation for the observed discordant phenotype seen in some cases of MC twins [Bourthoumieu et al., 2006; Charles, 2006; Malan et al., 2006] Despite their separate origin, MC/DZ twins may demonstrate mixed blood genotypes, with the genotype from each twin represented in each twin’s circulation, and may be discordant for their phenotype. This is due to confluent placental circulation [Bourthoumieu et al., 2006]. This has been referred to as “confined-blood chimerism.” This is relatively common compared to solid tissue chimerism, which to our knowledge, has only been demonstrated in two reports [Ginsberg et al., 2005; Souter et al., 2007]. Most of the reported cases are associated with the use of assisted reproductive technology (ART), but this might represent ascertainment bias [Quintero et al., 2003; Souter et al., 2003; Williams et al., 2004; Ginsberg et al., 2005; Aoki et al., 2006; Souter et al., 2007; Walker et al., 2007; Ekelund et al., 2008; Hawcutt et al., 2011; Chen et al., 2013; Kanda et al., 2013]. We present a case of normally conceived sex-discordant MC/DZ twins, with identical blood karyotype but chimeric skin genotype in one of the twins, which suggest an atypical mechanism of twinning.
Ó 2015 Wiley Periodicals, Inc.
Twin A is a male who was evaluated at age 2 months for aortic stenosis and hypospadias. A blood karyotype showed two cell lines (46,XY/46,XX). This prompted us to evaluate twin B, a phenotypically normal girl who also had two blood cell lines (46,XX/46,XY). Both twins were evaluated using blood karyotype, array comparative genomic hybridization with single nucleotide polymorphisms (aCGHþSNP), interphase FISH X/Y, skin karyotype, and blood and buccal microsatellite analyses. Supplemental analysis included the male’s skin microsatellites, parental microsatellites and molecular testing for single gene sex-reversal and hormonal studies.
Prenatal History The patients were born to a 21-year-old mother G4P4A1 after natural conception. Prenatal course was uncomplicated with no prenatal exposures. The twins were born by cesarian at 39 weeks of gestation. Prenatal ultrasound study revealed the presence of a single placenta but no evidence of twin–twin transfusion. Birth weights were 2.3 kg for the boy and 2.1 kg for the girl. Macroscopic and microscopic placental pathology revealed a monochorionic/ diamniotic pregnancy.
Correspondence to: David Rodriguez-Buritica, M.D., 431 Fannin Street, MSB 3.144, Houston, Texas 77030. E-mail: [email protected] Article first published online in Wiley Online Library (wileyonlinelibrary.com): 23 February 2015 DOI 10.1002/ajmg.a.37022
872
RODRIGUEZ-BURITICA ET AL.
873
TABLE I. Results of Cytogenetic and Endocrine Studies of the Twins TEST Blood karyotype Skin karyotype Blood interphase FISH X/Y analysis Blood aCGHþSNP array
SRY DHH DAX1 LH (mIU/ml) FSH (mIU/ml) Testosterone (ng/dl) Estradiol (pg/ml) AMH (ng/dl)
Male twin(A) at 2 months 46,XY [14]/46,XX [16]
Male twin(A) at 11 months 46,XY [18]/46,XX [12]
XY in 86/200 cells (43%) XX in 114/200 cells (57%)
Female twin (B) at 3 months 46,XX [9]/46,XY [21] 46, XX [32] XX in 89/200 cells (44.5%) XY in 111/200 cells (55.5%)
Female twin (B) at 10 months XX in 79/200 cells (39.5%) XY in 121/200 cells (60.5%)
