Difficulties in the prenatal diagnosis of microcephaly.

Our objective was to determine whether the diagnosis of microcephaly present at birth is apparent using standard biometry in the second trimester. Fetuses with prenatally suspected microcephaly (biparietal diameter > or = 3 standard deviations below mean) who had a first sonogram prior to 22 weeks' gestation and a confirmation of microcephaly after birth were included in the study. We excluded all fetuses who had neural tube defects or other major associated abnormality that would lead to a suspicion of microcephaly. We therefore included fetuses who either had normal-appearing brains sonographically or intracranial calcifications as the only sonographic abnormality seen prior to 22 weeks' gestation. Seven fetuses met these criteria. One fetus was diagnosed as having microcephaly prior to 22 weeks' gestation. The other six fetuses had a normal head size prior to 22 weeks' gestation and were diagnosed as having microcephaly at 27 weeks' gestation and later. Only one of the seven fetuses had a karyotypic abnormality. We conclude that the prenatal diagnosis of microcephaly is not excluded by normal biometry on second trimester sonography.     

Early prenatal diagnosis by celocentesis.

BACKGROUND: Celocentesis is the ultrasound-guided aspiration of fluid from the extra-amniotic cavity at 7-8 weeks of gestation. This paper reports on the clinical application of celocentesis for early prenatal diagnosis. METHODS: Celocentesis was successfully performed in nine pregnancies and 1-2 mL of fluid were obtained after one needle insertion. The indications were prenatal diagnosis of beta-thalassemia or sickle cell disease (n = 6), Marfan syndrome (n = 1) and paternity testing (n = 2). Molecular biological techniques were used to analyze the celomic fluid and this was successfully carried out in all cases. RESULTS: In two cases pregnancy termination was performed at the request of the mother because in one case the fetus was found to have sickle cell anemia and in the second case paternity testing demonstrated that the father was not the woman's husband. In both cases the results were confirmed using the placental samples collected after pregnancy termination. In six of the seven pregnancies with desirable results, amniocentesis was performed at 16 weeks and the results were concordant with those obtained from celocentesis. All pregnancies were uneventful and resulted in the delivery of healthy and appropriately grown babies. CONCLUSION: Celocentesis may be a viable alternative to the currently used tests of chorionic villus sampling and amniocentesis.     

Microsatellite markers within --SEA breakpoints for prenatal diagnosis of HbBarts hydrops fetalis

BACKGROUND: We sought to develop a rapid prenatal diagnostic test for simultaneous detection of HbBarts hydrops fetalis and exclusion of maternal contamination. METHODS: We developed a multiplex quantitative fluorescent PCR (QF-PCR) test that detects the presence/ absence of 2 microsatellite markers (16PTEL05/16PTEL06) located within breakpoints of the Southeast Asia ((-SEA)) deletion. HbBarts hydrops fetalis ((-SEA/-SEA)) is diagnosed by absence of both markers, and maternal contamination of fetal DNA is excluded by absence of noninherited maternal alleles. Fetal and parental DNA samples from 50 families were analyzed in a blinded clinical validation study, and QF-PCR results were compared with their respective molecular genotypes. RESULTS: The multiplex QF-PCR results included correct diagnoses of HbBarts hydrops fetalis in 11 of the fetuses tested, correct verification as unaffected in 20 fetuses, and correct identification as either carriers (alphaalpha/(-SEA)) or unaffected homozygotes in 18. Misidentification as unaffected occurred for 1 carrier. Sensitivity for diagnosis of HbBarts hydrops fetalis was 100% [lower 95% confidence interval, 76.2%], and specificity was 100% (lower 95% confidence interval, 92.6%). None of the samples tested showed any traces of noninherited maternal alleles; thus false-positives because of maternal contamination were eliminated. CONCLUSIONS: In this QF-PCR method, detection of maternally and paternally inherited fetal alleles allowed diagnosis of the double-deletion syndrome, and the ability to differentiate between these alleles allowed simultaneous exclusion of maternal contamination of the fetal genetic material. This novel strategy using cell-free fetal DNA in maternal plasma could form the basis for noninvasive testing for HbBarts hydrops fetalis.     

Meckel-Gruber syndrome. Importance of prenatal diagnosis

Prenatal sonographic findings are reported in six fetuses with the Meckel-Gruber syndrome to illustrate the variety of sonographic findings associated with this disorder and to emphasize the importance of prenatal sonography in helping to establish the correct diagnosis. All six fetuses demonstrated evidence of renal cystic dysplasia. In five cases the kidneys were large and echogenic, demonstrating small discrete cysts in the range of 2 to 5 mm. The remaining fetus demonstrated unilateral renal cystic dysplasia and contralateral renal agenesis. Oligohydramnios was noted in all cases and was evident as early as 14 weeks. An occipital cephalocele was demonstrated on sonography in each case although the size and contents of the cephalocele varied significantly. Two fetuses, both in the same family, also demonstrated a cystic mass in the posterior fossa and partial absence of the cerebellum consistent with a Dandy-Walker variant or cerebellar hypoplasia. The concurrence of marked oligohydramnios and bilateral severe renal anomalies should initiate a search for anomalies of the central nervous system indicative of the Meckel-Gruber syndrome. Recurrence of Meckel-Gruber syndrome may be evaluated as soon as 14 weeks, but it may not be reliably excluded until 20 weeks.     

Early sonographic prenatal diagnosis of seizures.

Fetal seizures are an unusual phenomenon. When diagnosed by ultrasonography, they are frequently associated with malformations and carry a poor prognosis. We describe first trimester seizures in two siblings with arthrogryposis multiplex congenita. In both cases, convulsions appeared before other sonographic signs of the disease. Review of the literature revealed 11 other cases of fetal seizures diagnosed by ultrasound, all later in gestation. Fetal seizures may be the first manifestation of defective neural and motor development. Therefore, in pregnancies at high risk for neuromuscular disease, early sonographic evaluation of fetal motility, in addition to the anatomical survey, is advised.     

Johanson-Blizzard syndrome: a prenatal ultrasonographic diagnosis.

Johanson-Blizzard syndrome is a rare autosomal recessive disorder characterized by aplasia of alae nasi, pancreatic insufficiency, aplasia cutis, anorectal anomalies and postnatal growth restriction. In this case report, we describe the prenatal sonographic findings of Johanson-Blizzard syndrome in a 21-week pregnancy of a consanguineous couple. Sonographic findings of aplastic alae nasi (beak-like nose) and dilated sigmoid colon led to the prenatal diagnosis. This is the first report of the prenatal sonographic diagnosis of Johanson-Blizzard syndrome.     

Early prenatal diagnosis of axillary cystic hygroma.

Fetal axillary cystic hygroma has been reported rarely and only as a sonographic finding late in gestation. A retrospective study of 19,200 early second trimester screening ultrasonograms for anomalies revealed five cases of axillary cystic hygroma. All of the axillary hygromas were small, transient, nonloculated cysts. Three cysts were associated with chromosomal abnormalities: trisomy 21 in two cases and a single case of trisomy 18 in which structural abnormalities also were detected. Early fetal axillary cystic hygroma appears to be different from postnatal axillary cysts on the basis of differences in prevalence, structure, and appearance. It also may be a normal variant in the development of the fetal lymphatic system.