Incidentally Identified Twin Chimerism: A Case Series
Clinical Genetics and Therapeutics
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Primary Categories:
- Clinical- Pediatric
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Secondary Categories:
- Clinical- Pediatric
Introduction:
Chimerism is a rare phenomenon whereby an individual has cells containing DNA from different zygotes. Twin chimeras arise when two zygotes do not undergo fusion but exchange cells and genetic material during development. This has been documented in both monochorionic diamniotic twins and dichorionic diamniotic twins, where chimerism is thought to occur through placental anastomoses and subsequent vascular exchange. Data regarding health complications in chimeras, if any, are lacking. Here we present a series of incidentally identified chimeras identified at our institution.
Methods:
Methods: Subjects were referred for clinical genetic evaluations at Kaiser Permanente. Cytogenetic analyses were performed within Kaiser Permanente
Results:
Case Reports:
Family 1:
A phenotypically normal 37 year old G3P2 woman was referred for sex discrepancy on her recent cell free fetal DNA screen obtained in early pregnancy achieved via IVF with an embryo that was known to be XX from the PGT-A screen. Family history revealed that her twin sister had a similar scenario during her last pregnancy with her cell free DNA screening positive for male fetus, but the subsequent amniocentesis revealing a normal female microarray. During that evaluation her twin sister also had a peripheral karyotype which showed 46,XY[16]/46,XX[4]. We obtained a peripheral karyotype on our proband which revealed 46,XY[14]/46,XX[6]. A SNP array was significant for an admixture of cells, arr(XX)[37%],(XY)[63%]. The SNP array data revealed that the XX and XY cell lines contained a different maternal X chromosome, leading to suspicion of chimerism as a result of multiple gestation with a vanishing male triplet.
Family 2:
Otherwise healthy nonidentical 11 year old twins were evaluated for proportionate short stature. They were conceived via in vitro fertilization which resulted in a dichorionic-diamniotic pregnancy. Prenatal ultrasound was consistent with posterior placental fusion. On exam no dysmorphic features were evident. The external genitalia were unremarkable. Height in the male was 1% and 3% in the female. Chromosome analysis was first performed on a blood specimen in the female to rule out Turner syndrome and revealed a chimeric karyotype described as chi 46,XY[13]/46,XX[7]. A subsequent karyotype on the male revealed chi 46,XY[15]/46,XX[7]. Whole-genome microarray analysis was then complete in both twins which confirmed the presence of XX/XY chimerism, designated as arr(XX)[~32%],(XY)[~68%] in the female and arr(XX)[40%],(XY)[60%],(1-22)x2 in the male.
Family 3:
A 25 year old G1P0 pregnant woman was evaluated for a spontaneous di-di twin pregnancy with IUGR of Twin A. No other malformations were identified on prenatal US. At birth, Twin B had normal female phenotype and Twin A was normal male phenotype. Chromosome analysis revealed 46,XX[16]/46,XY[4] in Twin B and 46,XX[10]/46,XY[10] in Twin A. Repat chromosome analysis 1 year later yielded similar results. Both twins went onto have normal growth and development.
Conclusion:
Conclusion:
Twin chimerism is a rare phenomenon. Here we present healthy and nonsyndromic twin pairs who were incidentally identified to be chimeras. No serious health issues arose in our subjects. Fertility was not impacted in the first pair. Chimerism occurs when an individual's cells come from two or more zygotes. This differs from mosaicism in which an individual's cells come from a single zygote but have different genotypes. Chimerism appears to be uncommon in twins, but the true frequency is not known. Twin chimerism may be important to identify as chimeras may have higher risks of autoimmune disorders, transfusion reactions or receiving inaccurate genetic testing results.
Chimerism is a rare phenomenon whereby an individual has cells containing DNA from different zygotes. Twin chimeras arise when two zygotes do not undergo fusion but exchange cells and genetic material during development. This has been documented in both monochorionic diamniotic twins and dichorionic diamniotic twins, where chimerism is thought to occur through placental anastomoses and subsequent vascular exchange. Data regarding health complications in chimeras, if any, are lacking. Here we present a series of incidentally identified chimeras identified at our institution.
Methods:
Methods: Subjects were referred for clinical genetic evaluations at Kaiser Permanente. Cytogenetic analyses were performed within Kaiser Permanente
Results:
Case Reports:
Family 1:
A phenotypically normal 37 year old G3P2 woman was referred for sex discrepancy on her recent cell free fetal DNA screen obtained in early pregnancy achieved via IVF with an embryo that was known to be XX from the PGT-A screen. Family history revealed that her twin sister had a similar scenario during her last pregnancy with her cell free DNA screening positive for male fetus, but the subsequent amniocentesis revealing a normal female microarray. During that evaluation her twin sister also had a peripheral karyotype which showed 46,XY[16]/46,XX[4]. We obtained a peripheral karyotype on our proband which revealed 46,XY[14]/46,XX[6]. A SNP array was significant for an admixture of cells, arr(XX)[37%],(XY)[63%]. The SNP array data revealed that the XX and XY cell lines contained a different maternal X chromosome, leading to suspicion of chimerism as a result of multiple gestation with a vanishing male triplet.
Family 2:
Otherwise healthy nonidentical 11 year old twins were evaluated for proportionate short stature. They were conceived via in vitro fertilization which resulted in a dichorionic-diamniotic pregnancy. Prenatal ultrasound was consistent with posterior placental fusion. On exam no dysmorphic features were evident. The external genitalia were unremarkable. Height in the male was 1% and 3% in the female. Chromosome analysis was first performed on a blood specimen in the female to rule out Turner syndrome and revealed a chimeric karyotype described as chi 46,XY[13]/46,XX[7]. A subsequent karyotype on the male revealed chi 46,XY[15]/46,XX[7]. Whole-genome microarray analysis was then complete in both twins which confirmed the presence of XX/XY chimerism, designated as arr(XX)[~32%],(XY)[~68%] in the female and arr(XX)[40%],(XY)[60%],(1-22)x2 in the male.
Family 3:
A 25 year old G1P0 pregnant woman was evaluated for a spontaneous di-di twin pregnancy with IUGR of Twin A. No other malformations were identified on prenatal US. At birth, Twin B had normal female phenotype and Twin A was normal male phenotype. Chromosome analysis revealed 46,XX[16]/46,XY[4] in Twin B and 46,XX[10]/46,XY[10] in Twin A. Repat chromosome analysis 1 year later yielded similar results. Both twins went onto have normal growth and development.
Conclusion:
Conclusion:
Twin chimerism is a rare phenomenon. Here we present healthy and nonsyndromic twin pairs who were incidentally identified to be chimeras. No serious health issues arose in our subjects. Fertility was not impacted in the first pair. Chimerism occurs when an individual's cells come from two or more zygotes. This differs from mosaicism in which an individual's cells come from a single zygote but have different genotypes. Chimerism appears to be uncommon in twins, but the true frequency is not known. Twin chimerism may be important to identify as chimeras may have higher risks of autoimmune disorders, transfusion reactions or receiving inaccurate genetic testing results.