Fetal Presentation of Walker-Warburg Syndrome with Compound Heterozygous POMT2 Missense Mutations.

Background: Walker-Warburg syndrome (WWS) (OMIM #236670) is an autosomal recessive disorder characterized by congenital muscular dystrophy, hydrocephalus, cobblestone lissencephaly, and retinal dysplasia. The main genes involved are: POMT1, POMT2, POMGNT1, FKTN, LARGE1, and FKRP. Case report: We present a fetus with WWS showing at ultrasound severe triventricular hydrocephalus. Pregnancy was legally terminated at 21 weeks +2 days of gestation. In vivo and postmortem magnetic resonance revealed corpus callosum agenesis and cerebellar hypoplasia. Cobblestone lissencephaly was observed at post-mortem. Next generation sequencing (NGS) of 193 genes, performed on fetal DNA extracted from amniocytes, detected two heterozygous mutations in the POMT2 gene. The c.1238G > C p.(Arg413Pro) mutation was paternally inherited and is known to be pathogenic. The c.553G > A p.(Gly185Arg) mutation was maternally inherited and has not been previously described. Conclusion: Compound heterozygous mutations in the POMT2 gene caused a severe cerebral fetal phenotype diagnosed prenatally at midgestation allowing therapeutic pregnancy termination.

Prenatal diagnosis versus first-trimester screening of trisomy 21 among pregnant women aged 35 or more.

OBJECTIVE: To compare the policy of prenatal diagnosis versus first trimester screening of trisomy 21 among pregnant women of advanced age. METHODS: A retrospective study was conducted on patients aged ≥35 divided in two groups: patients who requested first trimester combined test and only in case of screen-positive result underwent invasive testing (group A); patients undergoing chorionic villous sampling or amniocentesis as first investigation (group B). The following outcome variables were compared: antenatal detection of trisomy 21, occurrence of trisomy 21 at birth, miscarriage rate, hospitals' costs. RESULTS: 4527 women were included. Of these, 534 (11.80%) underwent T21 screening whereas 3993 (88.20%) requested primary invasive testing. In group A, 64 combined test were positive (11.99%) and 8 trisomy 21 cases were diagnosed (1.50%); the loss of euploid fetuses after invasive procedure was 4.55% (2/44). No false-negative case was observed. In group B 57 cases of trisomy 21 were diagnosed (1.43%), and pregnancy loss rate of chromosomally normal fetuses was 0.45% (17/3806). The estimated cost was, respectively, 67.720€ for the primary screening versus 1.996.500€ for direct prenatal diagnosis. CONCLUSION: First trimester screening of trisomy 21 is highly accurate and cost saving among women ≥35.

Screening for pre-eclampsia by using changes in uterine artery Doppler indices with advancing gestation.

OBJECTIVE: The aim of the study was to assess the relationship of changes in uterine artery (UtA) Doppler pulsatility indices (PI) between first and second trimesters and the subsequent development of pre-eclampsia. METHODS: A retrospective study of singleton pregnancies undergoing both first and second trimesters UtA Doppler screening between 2002 and 2009 was conducted. Multiples of median of UtA Doppler PI were used for developing indices describing UtA changes between the two trimesters. Receiver-operating characteristics curves (ROC) were calculated for multiple comparisons. RESULTS: Three thousand five hundred sixty women had UtA Doppler screening in the first and second trimesters. Eleven women were excluded because of termination of pregnancy before 24 weeks. Out of the 3549 women recruited, 126 developed Pre-eclampsia (PE; 22 early PE delivered <34 weeks and 41 preterm PE delivered <37 weeks). The best index for predicting pre-eclampsia was the difference between the mean second trimester and mean first trimester UtA PI (areas under the ROC for early PE and preterm PE of 0.851 and 0.786, respectively). CONCLUSION: Changes of UtA resistance between the first and second trimesters can be calculated as the difference between UtA PI at these gestations. The data of this study demonstrate that the difference in mean PI is the best index in predicting early PE and preterm PE.