Prenatal diagnosis of a trisomy 7/trisomy 13 mosaicism
© Amsterdam et al; licensee BioMed Central Ltd. 2012
Received: 7 December 2011
Accepted: 27 January 2012
Published: 27 January 2012
Double aneuploidy mosaicism of two different aneuploidy cell lines is rare. We describe for the first time a double trisomy mosaicism, involving chromosomes 7 and 13 in a fetus presenting with multiple congenital anomalies. No evidence for chimerism was found by DNA genotyping. The origin of both trisomies are consistent with isodisomy of maternal origin. Therefore, it is most likely that the double trisomy mosaicism arose from two independent events very early in embryonic development. The trisomy 7 and 13 cells were shown to be of maternal origin.
Keywordsdouble autosomal aneuploidy mosaicism trisomy 7 trisomy 13
Double aneuploidy mosaicism of two different aneuploidy cell lines is a rare event . The most frequently described combinations are a monosomy X cell line with a cell line containing a trisomy of an autosome. In literature, mosaicism of a monosomy X cell line with either a trisomy 7, 8, 10, 13, 18 or 21 have been reported [2–7]. Double autosomal trisomies are even more sporadic, and to date combinations of trisomies of the chromosomes 8 and 14, chromosomes 8 and 21, chromosomes 13 and 18, chromosomes 13 and 21, and chromosomes 18 and 21 have been reported [1, 8–12].
Here, we present the first report of a double trisomy mosaicism involving chromosomes 7 and 13 in both amniotic fluid and subsequent FISH analysis of fibroblasts in a fetus presenting with multiple congenital anomalies.
A 17-year-old healthy woman of a non-consanguineous couple, gravida 1, para 0, was referred at 21+0 weeks' gestation because of multiple structural anomalies. There was no history of familial congenital anomalies or drug use. The pregnancy was unplanned but welcome. A dating scan had been performed at 8 weeks' gestation. A 12 weeks' scan was not performed since the parents did not wish screening for Down syndrome. The fetus showed growth restriction with a large bilateral cleft lip and palate with severe micrognathia. The caput showed mild brachycephaly, with an enlarged cisterna magna (> p95). The left little finger was bowed and there were mild clubfeet. Following genetic counselling the patient elected to have an amniocentesis for karyotyping. Moreover, the parents requested a termination of pregnancy.
Labour was induced at 22+2 weeks and a female baby was born, who died shortly after birth. Her birth weight was 370 g. Autopsy confirmed the bilateral cleft lip and palate as well as the retrognathia, and revealed an internal malrotation of the digestive tract with the ileocecal valve situated in the upper abdomen on the left side and bicornate uterus. All body and organ measures were within normal range for the given gestational age. X-ray showed no developmental anomalies of the skeletal system. Brain autopsy found no cerebral developmental anomalies, except for microglial upregulation, most likely as a result of hypoxic damage. Finally, the placenta showed no abnormalities, with the exception of a slight degeneration.
Fetal chromosome analysis of in situ cultured amniocytes revealed a double trisomy mosaicism: mos 47, XX, +7/47, XX, +13. A trisomy 13 was seen in 75% of the amniocytes (18/24 metaphases) and in three different cultures. The remaining 25% of the cells (6/24 metaphases) showed a trisomy 7, also in two different cultures. There was no cell line with a normal karyotype, nor did we detect cells with a trisomy for both chromosome 13 and 7.
DNA genotyping using 16 STR markers (Powerplex 16 kit Promega) showed the presence of a single maternal and a single paternal allele in the DNA extracted from amniotic fluid cells for all informative markers, without evidence for chimerism (paternal allele, 14 markers informative; maternal allele 9 markers informative), suggesting that the trisomy 7 and the trisomy 13 cell lines were not a result of two different zygotes.
To establish the origin of the chromosomes 7 and 13, DNA analyses was performed. Seven markers for chromosome 13 (D13S217, D13S171, D13S263, D13S159, D13S158, D13S173, D13S285) were informative and showed an increased contribution of the maternally inherited allele (confirmed by QF-PCR, Tepnel). Also, four informative chromosome 7 markers (D7S664, D7S2427, D7S2476, D7S483) showed an increased contribution of the maternally inherited allele. The results are consistent with an isodisomy 7 and an isodisomy 13 of maternal origin. Since no heterodisomic markers were seen, a postfertilization error very early in embryonic development seems most plausible. In literature, no evidence was found for higher risks for chromosomal trisomies in women under the age of 20 .
Contribution of trisomy 7 and trisomy 13 cells to the abnormalities seen at autopsy.
assumed to be attributed by trisomy of chromosome
bilateral cleft lip and palate
enlarged cisterna magna
left little finger bowed
malrotation of the digestive tract
We describe a double aneuploid foetus with two different trisomic cell lines: one with a trisomy 7 (approximately 26%) and one with a trisomy 13 (approximately 70%). No evidence for chimerism was found by DNA genotyping. The origin of both trisomies are consistent with isodisomy of maternal origin. Therefore, it is most likely that the double aneuploidy seen arose from two independent events very early in embryonic development.
Written consent was obtained from the parents of the patient for publication of this case report and accompanying images.
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