OBJECTIVE: We present mosaic trisomy 16 at amniocentesis in a pregnancy associated with positive non-invasive prenatal testing (NIPT) for trisomy 16, placental trisomy 16, intrauterine growth restriction (IUGR), intrauterine fetal death (IUFD), cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes and uncultured amniocytes, and prenatal progressive decrease of the aneuploid cell line.
METHODS: A 26-year-old, primigravid woman underwent amniocentesis at 17 weeks of gestation because of positive NIPT for trisomy 16 at 12 weeks of gestation. Amniocentesis revealed a karyotype of 47,XX,+16 [10]/46,XX[17], and simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed the result of arr (16) × 3 [0.43] consistent with 43% mosaicism for trisomy 16. She was referred for genetic counseling at 19 weeks of gestation, and a fetus with IUGR was noted to have a size equivalent to 16 weeks of gestation. At 23 weeks of gestation, the fetus manifested oligohydramnios, fetal cardiomegaly and severe IUGR (fetal size equivalent to 20 weeks of gestation). Repeat amniocentesis revealed a karyotype of 46,XX (20/20 colonies) in cultured amniocytes and mosaic trisomy 16 by aCGH in uncultured amniocytes. aCGH analysis on uncultured amniocytes revealed the result of arr 16p13.3q24.3 × 2.3, consistent with 30% (log2 ratio = 0.2) mosaicism for trisomy 16. Quantitative fluorescence polymerase chain reaction (QF-PCR) assays on the DNA extracted from parental bloods and uncultured amniocytes excluded uniparental disomy (UPD) 16. The parental karyotypes were normal. IUFD was noted at amniocentesis. The pregnancy was subsequently terminated, and a 288-g female fetus was delivered with no phenotypic abnormalities. The umbilical cord had a karyotype of 46,XX (40/40 cells), and the placenta had a karyotype of 47,XX,+16 (40/40 cells). QF-PCR assays of the placenta confirmed a maternal origin of trisomy 16.
CONCLUSIONS: Mosaic trisomy 16 at amniocentesis can be associated with positive NIPT for trisomy 16, placental trisomy 16, IUGR, IUFD, cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes, and prenatal progressive decrease of the aneuploid cell line.

Trisomy 16 is the most common autosomal trisomy found in spontaneous abortions with mosaic versions seen in survivors. However, surviving children have multiple congenital defects and are at risk of growth and developmental delay. We report an additional case of mosaic trisomy 16 diagnosed by amniocentesis and confirmed after birth. Our patient is the first documented case of living mosaic trisomy 16 with the malformation constellation of lung agenesis, left pulmonary artery agenesis, congenital heart defects, and ipsilateral radial ray and limb abnormalities, expanding the phenotype of this rare condition. Additionally, this individual\'s unique combination of lung and cardiac defects caused morbidities that were challenging to manage and complicated family counseling as well.

OBJECTIVE: We present prenatal diagnosis of mosaic trisomy 16 by amniocentesis in a pregnancy associated with an abnormal first-trimester screening result, intrauterine growth restriction (IUGR) and a favorable outcome.
METHODS: A 27-year-old woman underwent amniocentesis at 18 weeks of gestation because of an abnormal first-trimester screening result with maternal serum free β-hCG of 1.474 multiples of the median (MoM), pregnancy associated plasma protein-A (PAPP-A) of 0.122 MoM and placental growth factor (PlGF) of 0.101 MoM, and a Down syndrome risk of 1/45. Amniocentesis revealed a karyotype of 47,XY,+16 [9]/46,XY [16] and an abnormal array comparative genomic hybridization (aCGH) result of arr (16) × 3 [0.54] compatible with 54% mosaicism for trisomy 16 in uncultured amniocytes. At 24 weeks of gestation, repeat amniocentesis revealed a karyotype of 47,XY,+16 [4]/46,XY [16] and an aCGH result of arr 16p13.3q24.3 (96,766-90,567,357) × 2.25 with a log2 ratio = 0.2 compatible with 20-30% mosaicism for trisomy 16 in uncultured amniocytes. Quantitative fluorescent polymerase chain reaction (QF-PCR) excluded uniparental disomy (UPD) 16. Interphase fluorescence in situ hybridization (FISH) analysis on uncultured amniocytes revealed 19.4% (12/62 cells) mosaic trisomy 16. Prenatal ultrasound revealed IUGR. At 36 weeks of gestation, a phenotypically normal baby was delivered with a body weight of 1900 g. The cord blood had a karyotype of 46,XY. QF-PCR analysis confirmed biparentally inherited disomy 16 in the cord blood and maternal-origin of trisomy 16 in the placenta. When follow-up at age two months, FISH analysis on 101 buccal mucosal cells and 32 urinary cells revealed no signal of trisomy 16.
CONCLUSIONS: Mosaic trisomy 16 at amniocentesis can be associated with IUGR and an abnormal first-trimester screening result with low PAPP-A and low PlGF. Mosaic trisomy 16 without UPD 16 at amniocentesis can have a favorable outcome, and the abnormal triosmy 16 cell line may disappear after birth.

OBJECTIVE: We present prenatal diagnosis of maternal uniparental disomy (UPD) 16 associated with mosaic trisomy 16 at amniocentesis, and pericardial effusion and intrauterine growth restriction (IUGR) in the fetus.
METHODS: A 38-year-old woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age, and the result was 47,XX,+16[2]/46,XX[54]. Simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed 14% mosaicism for trisomy 16 and a paternally inherited 319-kb microdeletion of 15q11.2 encompassing the genes of TUBGCP5, CYFIP1, NIPA2 and NIPA1. Prenatal ultrasound revealed persistent left superior vena cava, pericardial effusion and severe IUGR. Cordocentesis at 23 weeks of gestation revealed a karyotype of 46,XX, but polymorphic DNA marker analysis revealed maternal UPD 16. Repeat amniocentesis was performed at 27 weeks of gestation and revealed a karyotype of 46, XX in 21/21 colonies. Molecular cytogenetic analysis on uncultured amniocytes revealed 22.4% mosaicism (26/116 cells) for trisomy 16 on interphase fluorescence in situ hybridization (FISH) analysis, and 20% mosaicism for trisomy 16 on aCGH. Polymorphic DNA marker analysis on the DNAs extracted from uncultured amniocytes and parental bloods revealed maternal UPD 16. The pregnancy was subsequently terminated, and a fetus was delivered with facial dysmorphism and severe IUGR. The umbilical cord had a karyotype of 47,XX,+16[28]/46,XX[16]. Polymorphic DNA marker analysis on placenta confirmed a maternal origin of trisomy 16.
CONCLUSIONS: Cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes may present in mosaic trisomy 16 at amniocentesis. Prenatal diagnosis of mosaic trisomy 16 should alert the association of maternal UPD 16 which may be associated with congenital heart defects and severe IUGR on prenatal ultrasound.