Antenatal description of large 4q13.2q21.23 deletion and outcomes.

BACKGROUND: 4q21 microdeletion syndrome is an emergent non-recurrent genomic disorder characterized by facial dysmorphy, progressive growth retardation, severe intellectual deficit, and absent or severely delayed speech. Deletions occur in clusters along 4q interstitial or terminal regions. 4q chromosomal aberrations are variable in type, size, and breakpoint. Genotype-phenotype correlation is a challenging task. The recurrent antenatal feature associated a posteriori with this syndrome is intrauterine growth retardation. There are very few precise antenatal descriptions of this syndrome. METHODS: We report here the first antenatal history of one of the largest deletion of this region. RESULTS: Our case harbored a 16.9 Mb deletion encompassing 135 protein coding genes including 20 OMIM morbid genes involved in neurological and cognitive abilities. Those breakpoints overlap two clusters of described microdeletion syndromes of cytogenetic band 4q13 and 4q21. CONCLUSION: From the end of the second trimester, set of call signs associated with this syndrome can be completed by: excess of amniotic fluid, mild growth retardation, short long bones, bony anomalies of the extremities, and bulging cheeks. So, emphasis should be placed on the examination of the extremities, and the face during the routine targeted prenatal ultrasound.

Analysis of blood from Zika virus-infected fetuses: a prospective case series.

BACKGROUND: Zika virus has spread through the Americas and the Caribbean since early 2015 and was rapidly declared a Public Health Emergency of International Concern by WHO because of the potential association with fetal anomalies. We analysed fetal and maternal fluids and tissues in fetuses with confirmed Zika virus infection prospectively monitored in Martinique, a French Caribbean island. METHODS: Since the beginning of the Zika virus outbreak in Martinique, all pregnant women undergo monthly fetal ultrasound examination surveillance. In this study, we prospectively studied all patients with fetal anomalies and a positive amniotic fluid for Zika virus by RT-PCR. Maternal and fetal blood, urine, amniotic fluid, placenta, and fetal tissues were tested for Zika virus by RT-PCR. Fetal blood was analysed to identify haematological and biological anomalies. FINDINGS: Between Jan 1, 2016, and Nov 10, 2016, we recruited eight cases of Zika virus infection. All but two cases were symptomatic during the first trimester. Fetal anomalies were only detected after 20 weeks' gestation. After an initial positive result, amniocentesis became negative in two cases and fetal blood was transiently Zika virus-positive in six cases. Fetal blood analyses showed a cholestatic pattern, anaemia, and infectious response. INTERPRETATION: Normalisation of amniotic fluid and fetal blood for Zika virus, as well as maternal blood and urine, shows the limitations of the performance of these investigations, due to the possibility of false negative results. Abnormal fetal blood needs to be investigated further to establish prognostic factors of severe Zika virus infections. FUNDING: None.

Ultrasound imaging for identification of cerebral damage in congenital Zika virus syndrome: a case series.

BACKGROUND: Zika virus is a novel teratogenic agent associated with cerebral anomalies. Because of the challenges associated with assessment of antenatal diagnosis and prognosis in fetuses, screening for other congenital infections mostly relies on ultrasound. We aimed to assess whether a similar approach might be adequate for Zika virus congenital syndrome provided that early markers of infection and adequate timing for screening are established. METHODS: For this case series we reviewed all pregnant women who had a laboratory-confirmed Zika virus infection in their first trimester or early second trimester and abnormal fetal ultrasound findings who were managed at the Pluridisciplinary Center for Prenatal Diagnosis of Martinique during the Zika virus epidemic (Jan 1, 2016, to Nov 10, 2016) in Martinique, a French Caribbean island. Ultrasound imaging was done with GE Healthcare Voluson E10 and E8 machines with abdominal and vaginal probes. FINDINGS: We analysed 14 cases of pregnant women with confirmed Zika virus infection and fetal abnormalities of the brain, and 31 ultrasound imaging results. Between 16 and 20 weeks of gestation, four (33%) of 12 fetuses had an abnormal ultrasound examination. Anomalies were detected in nine (90%) of the ten fetuses from whom ultrasound images were obtained between 20 and 24 weeks of gestation. All five remaining fetuses at 24-28 weeks of gestation, and all four after 28 weeks, had severe anomalies. Major anomalies identified were ventriculomegaly (12 fetuses, 86%), cortical atrophy (11, 79%), calcifications (ten, 71%; particularly located at the corticosubcortical junction), and anomalies of the corpus callosum (ten, 71%). Prenatal assessment of head circumference measurement by imaging was not an effective screening tool for congenital Zika virus infection, with microcephaly only identified in nine (64%) fetuses. INTERPRETATION: Ultrasound monitoring appears to be a good screening strategy to monitor Zika virus-exposed pregnancies. Public health efforts should focus on scanning at 22-26 weeks of gestation. Identification of ventriculomegaly, cortical atrophy, calcifications, and anomalies of the corpus callosum should prompt laboratory screening for Zika virus. FUNDING: None.

Normal Range of Fetal Nasal Bone Length during the Second Trimester in an Afro-Caribbean Population and Likelihood Ratio for Trisomy 21 of Absent or Hypoplastic Nasal Bone.

OBJECTIVE: To establish the normal reference range of fetal nasal bone length (NBL) during the second trimester in an Afro-Caribbean population and the likelihood ratio (LR) for fetal trisomy 21. METHODS: Prenatal records of euploid, non-malformed singleton fetuses who underwent second-trimester ultrasonographic scans at 20-24 weeks of gestation were retrospectively analyzed for NBL and gestational age (GA). Only Afro-Caribbean couples were selected. The relationship between fetal NBL and GA was determined. The data of all fetuses with Down syndrome were provided by the French West Indies Register of Congenital Malformations (REMALAN). RESULTS: There was a significant linear association between fetal NBL and GA (R2 = 0. 354). The 50th percentile for NBL increased from 5.0 to 7.0 mm from week 20 to 24 of gestation. The nasal bone (NB) was absent or hypoplastic in 8.6% of the euploid fetuses and in 69.2% of the trisomy 21 fetuses. The LR for trisomy 21 of absent or hypoplastic NB in an Afro-Caribbean population was 8.02, but only 2.32 when this sign was isolated. CONCLUSION: The reference range for fetal NBL at 20-24 weeks of gestation in an Afro-Caribbean population and the LR for trisomy 21 of absent or hypoplastic NB differed from the other populations.