[First trimester screening for Down syndrome at Prima facie. A 6-year survey]. / Dépistage de la trisomie 21 au premier trimestre. Bilan de 6 années à Prima facie.

OBJECTIVE: To evaluate the results of screening for trisomy 21 by the combined risk of first trimester (as defined by the decree of June 23, 2009) in the Prima facie structure. METHODS: Single center study involving all patients that were seen for first trimester screening at Prima facie with singleton living pregnancy, not obtained by embryo donation, between 1 January 2009 and 31 December 2014. RESULTS: Eighteen thousand two hundred and fifty-one patients were included, of which underwent screening for trisomy 21 by the combined risk. One thousand and forty-six (6.1%) had a calculated risk higher than 1/250. Seventy-five were affected by trisomy 21, of whom 65 in the high risk group. The sensitivity and specificity of screening are 86.7% and 94.4%. The median nuchal translucency was 0.98 MoM. CONCLUSIONS: Screening for trisomy 21 by calculating the combined risk of first trimester enabled to detect 86.7% of trisomy 21 with a false positive rate of 5.6%.

A French collaborative survey of 272 fetuses with 22q11.2 deletion: ultrasound findings, fetal autopsies and pregnancy outcomes.

OBJECTIVE: The 22q11.2 deletion (del22q11.2) is one of the most common microdeletions. We performed a collaborative, retrospective analysis in France of prenatal diagnoses and outcomes of fetuses carrying the del22q11.2. METHODS: A total of 272 fetuses were included. Data on prenatal diagnosis, ultrasound findings, pathological features, outcomes and inheritance were analyzed. RESULTS: The mean time of prenatal diagnosis was 25.6 ± 6 weeks of gestation. Most of the diagnoses (86.8%) were prompted by abnormal ultrasound findings [heart defects (HDs), in 83.8% of cases]. On fetal autopsy, HDs were again the most common disease feature, but thymus, kidney abnormalities and facial dysmorphism were also described. The deletion was inherited in 27% of cases. Termination of pregnancy (TOP) occurred in 68.9% of cases and did not appear to depend on the inheritance status. However, early diagnosis was associated with a higher TOP rate. CONCLUSION: This is the largest cohort of prenatal del22q11.2 diagnoses. As in postnatally diagnosed cases, HDs were the most frequently observed abnormalities. However, thymus and kidney abnormalities and polyhydramnios should also be screened for in the prenatal diagnosis of del22q11.2. Only the time of diagnosis appeared to be strongly associated with the pregnancy outcome: the earlier the diagnosis, the higher the TOP rate.

Monozygotic twins discordant for 18q21.2qter deletion detected by array CGH in amniotic fluid.

Discordant chromosomal anomalies in monozygotic twins may be caused by various timing issues of erroneous mitosis and twinning events. Here, we report a prenatal diagnosis of heterokaryotypic monozygotic twins discordant for phenotype. In a 28-year-old woman, ultrasound examination performed at 26 weeks of gestation, detected intrauterine growth restriction and unilateral cleft lip and palate in twin B, whereas twin A had normal fluid, growth and anatomy. Molecular karyotyping in twin B identified a 18q21.2qter deletion, further confirmed by FISH analysis on amniocytes. Interestingly, in twin A, cytogenetic studies (FISH analysis and karyotype) on amniocytes were normal. Genotyping with microsatellite markers confirmed the monozygosity of the twins. At 32 weeks of gestation, selective termination of twin B was performed by umbilical cord coagulation and fetal blood samples were taken from the umbilical cord in both twins. FISH analyses detected mosaicism in both twins with 75% of cells being normal and 25% harboring the 18qter deletion. After genetic counseling, the parents elected to terminate the second twin at 36 weeks of gestation. In postmortem studies, FISH analyses revealed mosaicism on several tissues in both twins. Taking into account this observation, we discuss the difficulties of genetic counseling and management concerning heterokaryotypic monozygotic twins.

[Abnormal placental caryotype in severe intrauterine growth retardations (IUGR). Case report]. / Place du caryotype placentaire dans l'enquête étiologique des retards de croissance intra-utérins sévères précoces. A propos d'un cas.

Except for cases due to maternal hypertension, severe and early intrauterine growth retardations are most usually due to fetal abnormalities. We report a case of confined placental homogenous tetraploidy associated with major fetal growth retardation leading to the premature delivery of a life born baby with a normal caryotype. We discuss the interest of chorionic villus sampling in cases of unexplained severe fetal growth retardation.

Prenatal detection of a de novo terminal inverted duplication 4p in a fetus with the Wolf-Hirschhorn syndrome phenotype.

OBJECTIVES: To present the prenatal diagnosis of a de novo terminal inversion duplication of the short arm of chromosome 4 and a review of the literature. CASE: An amniocentesis for chromosome analysis was performed at 33 weeks' gestation because ultrasound examination showed a female fetus with multiple abnormalities consisting of severe intrauterine growth retardation, microcephaly, a cleft lip and renal hypoplasia. RESULTS: Cytogenetic analysis and FISH studies of the cultured amniocytes revealed a de novo terminal inversion duplication of the short arm of chromosome 4 characterized by a duplication of 4p14-p16.1 chromosome region concomitant with a terminal deletion 4p16.1-pter. The karyotype was thus: 46,XX, inv dup del (4)(:p14-->p16.1::p16.1-->qter). The parents opted to terminate the pregnancy. Fetopathological examination showed dysmorphic features and abnormalities consistent with a Wolf-Hirschhorn syndrome (WHS) diagnosis, clinical manifestations of partial 4p trisomy being mild. CONCLUSION: Although relatively rare, inverted duplications have been reported repeatedly in an increasing number of chromosomes. Only two previous cases with de novo inv dup del (4p) and one with tandem dup 4p have been reported, all of them associated with a 4pter deletion. We report the first case diagnosed prenatally. Breakpoints are variable, resulting in different abnormal phenotype. In our case, clinical manifestations resulted in a WHS phenotype.

Prenatal diagnosis of tetraploidy.

A pregnancy was terminated at 24 weeks of amenorrhea when tetraploidy (92 XXXX) was diagnosed in fetal blood subsequent to ultrasonographic detection of a polymalformation syndrome. The severity of the neurological deficit in tetraploid infants and their death before 2 years of age require that prenatal diagnosis by cordocentesis be performed for analysis of fetal blood in cases of equivocal and nonspecific polymalformation syndrome and justify that medically-induced termination of pregnancy is suggested in the event of intrauterine tetraploidy diagnosis.