Monozygotic twins discordant for trisomy 21 and maternal 21q inheritance: a complex series of events.
We report on a monochorionic/diamniotic twin pregnancy discordant for trisomy 21. Amniocentesis (at 13(5/7) weeks) was performed following ultrasound signs of hydrops and cystic hygroma in twin 1 (T1). Prenatal karyotype showed non-mosaic trisomy 21 in T1 (47,XX,+21[7]), and low-grade mosaic trisomy 21 in twin 2 (T2) (47,XX,+21[2]/46,XX[19]). Post mortem examination of fetal skin, kidneys and lungs confirmed trisomy 21 in T1 (47,XX,+21[548]) and the placenta (47,XX,+21[200]). T2 had a normal karyotype (46,XX[648]). Analysis of microsatellite polymorphisms in multiple samples from the placenta, hand, lungs, kidneys and the umbilical cords of both twins confirmed monozygosity for all loci tested, and trisomy 21 in T1. Unexpectedly, T1 and T2 inherited different maternal alleles for markers of the most distal 4 Mbp of 21q. At least four successive events are needed to explain the genetic status of both twins and include maternal MI premature chromatids separation or maternal II meiotic nondisjunction and post-zygotic events such as, chromosome rescue, nondisjunction, an/or recombination.
Dahoun
Sophie
S
Genetic Medicine, University Hospitals of Geneva, Geneva, Switzerland. sophie.dahoun@hcuge.ch
Gagos
Sarantis
S
Gagnebin
Maryline
M
Gehrig
Corinne
C
Burgi
Carole
C
Simon
Fabienne
F
Vieux
Chantal
C
Extermann
Philippe
P
Lyle
Robert
R
Morris
Michael A
MA
Antonarakis
Stylianos E
SE
Béna
Frédérique
F
Blouin
Jean-Louis
JL
D000649:Amniocentesis; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics*; D004200:Diseases in Twins; D004314:Down Syndrome / Q000235:genetics*; D005260:Female; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D007621:Karyotyping; D018895:Microsatellite Repeats; D009630:Nondisjunction, Genetic; D011110:Polymorphism, Genetic; D011247:Pregnancy; D011296:Prenatal Diagnosis; D014430:Twins, Monozygotic
D005819:Genetic Markers