Prenatal diagnosis in a family with mitochondrial acetoacetyl-coenzyme a thiolase deficiency with the use of the polymerase chain reaction followed by the heteroduplex detection method

Mitochondrial acetoacetyl-coenzyme A (CoA) thiolase deficiency is an organic aciduria which affects isoleucine and ketone body catabolism. GK16 (the index patient) was affected with this disorder and previous studies had revealed that GK16 was a compound heterozygote with IVS8(+1) gt to tt and A301P mutations. In a subsequent pregnancy, prenatal diagnosis was performed and the fetus's amniocytes were analysed by the polymerase chain reaction (PCR) followed by the heteroduplex detection method on a Mutation Detection Enhancement gel. The fetus was identified as a carrier of the IVS8(+1) mutation. We confirmed the diagnosis by immunoblot analysis of extracted amniocytes and gene analysis with blood filter paper after delivery. This is the first report of prenatal diagnosis of this disorder at the gene level.     

Prenatal sonographic diagnosis of autosomal recessive polycystic kidney disease (arpkd) during the early second trimester

Autosomal recessive polycystic kidney disease (ARPKD) is a rare hereditary disease with a high neonatal mortality. Currently, prenatal diagnosis is possible only during the second half of pregnancy, when bilaterally enlarged, echogenic kidneys are visible by ultrasound. We describe a case in which a diagnosis of ARPKD was sought in the first half of pregnancy. High-resolution ultrasonography revealed echogenic, normal-sized kidneys at 15+4 weeks. Microsatellite DNA analysis of a chorionic villus sample, parental blood, and blood of an affected sibling showed that the fetus had the maternal haplotype and a recombination of the paternal haplotype. Thus, no distinction between homo- and heterozygosity for the ARPKD mutation in the fetus was possible. A further ultrasound examination at 19+4 weeks confirmed the previous results, indicating that the fetus was likely to be affected. After termination of the pregnancy, the diagnosis was confirmed on microscopic examination.     

Prediction of an abnormal karyotype in fetuses with omphalocele

The aim of this study was to assess the value of ultrasonographic evaluation in predicting abnormal karyotypes in fetuses with omphalocele. Forty fetuses with antenatally diagnosed omphalocele and available karyotype results were reviewed. Ultrasound evaluation included herniation contents and size, and the detection of other anomalies. Nine of 40 consecutive fetuses had abnormal karyotypes: trisomy 18 (n = 5), trisomy 13 (n = 3), 47,XXX (n = 1). Only 1/25 with an extracorporeal liver versus 8/15 with an intracorporeal liver had abnormal chromosomes [P = 0·0006, RR = 0·14 (0·02 < RR <0·9)]. Small defects (<3 cm) were associated with abnormal karyotypes [P = 0·01, RR = 4·7 (1·4<RR <15·6)]. Finding concurrent malformations was highly associated with chromosomal anomalies [P = 0·00004, RR = 4·4 (2·3 < RR < 8·5)]. The presence of associated malformations, an intracorporeal liver, and a small herniation size are highly suggestive of an associated abnormal karyotype.     

Isolated fetal hydronephrosis: Beware the effect of bladder filling

The aim was to assess the role that fetal bladder size has in the determination of fetal hydronephrosis. Forty-three fetuses were evaluated for fetal hydronephrosis in the second trimester of pregnancy. Anteroposterior measurements of the renal pelvis were obtained with a full bladder and again when the bladder emptied in each fetus. Statistical analysis was performed using the Spearman rank order correlation coefficient to assess the relationship between bladder status and renal dilation. The anteroposterior size of the fetal renal pelvis diminished from 6.8 ± 1.8 mm on a full bladder scan to 4.5 ± 1.6 mm when the bladder was emptied (P<0.001). Fifty-three per cent of the fetuses whose renal pelvic measurements were 5 mm or more on a full bladder scan had normal-appearing renal pelvises when their bladders emptied. The status of the fetal bladder should be considered when evaluating fetal hydronephrosis.     

Ultrasound screening for chromosomal anomalies in the first trimester of pregnancy

For the last 6 years, sonographic signs for excessive fluid accumulation in the backs of 10- to 12-week-old fetuses have been looked for prior to transabdominal chorionic biopsy. In 1400 pregnancies, subsequent karyotype analyses revealed 28 cases of Down syndrome. In 15 ( = 54 per cent), a large fluid cushion over most of the back had been documented at the time of biopsy. Only a few chromosomally normal fetuses with the same peculiarity were observed. The cushion was also present in fetuses with trisomies 18 and 13 , and in Turner syndrome. Systematic first-trimester screening for nuchal fluid accumulation seems to be a recommended method for the detection of Down syndrome and other chromosome anomalies in young pregnant women at low risk. It compares favourably with current methods of maternal serum screening performed at 16–18 weeks which require a higher number of invasive procedures.     

Antenatal diagnosis of a congenital nasolacrimal duct cyst by ultrasonography: A case report

With proximal and distal obstruction to the lacrimal drainage system, mucus accumulates forming a cyst. In order to diagnose a nasolacrimal duct cyst antenatally, the sonographer must image the region adjacent to the orbits.     

Prenatal diagnosis and investigation of a fetus with chondrodysplasia punctata,ichthyosis, and Kallmann syndrome due to an Xp deletion

We report the prenatal diagnosis of a male fetus with X-linked recessive chondrodysplasia punctata (CDPX), steroid sulphatase (STS) deficiency, X-linked Kallmann syndrome (KAL), and a chromosome deletion at Xp22.31. Biochemical analysis of bone from this case indicates that CDPX is not a defect of vitamin K metabolism. Immunocytochemical study of the brain suggests that KAL is a defect in neuronal migration.     

Prenatal diagnosis of familial congenital pyloric atresia

Familial congenital pyloric atresia is a rare malformation of the fetal gastrointestinal tract. It usually manifests as maternal polyhydramnios and enlarged fetal stomach on ultrasound scan. Sonographic prenatal diagnosis and management of a pregnancy complicated by familial congenital pyloric atresia are presented.     

Prenatal diagnosis of gall bladder anomalies—report of 17 cases

We describe here 17 cases of fetal gall bladder anomalies, detected as early as the 14th week of gestation, out of 10 016 fetal systemic examinations performed by us in the last 6 years (015 per cent). In seven cases, agenesis of the fetal gall bladder was detected. The diagnosis was confirmed by post-abortal examination in five cases and in two post-partum. In six other cases, a left-sided gall bladder and in one case, a ‘floating’ gall bladder were detected at 15 weeks' gestation. In two cases, a septated or bilobed gall bladder was visualized. None of these 15 cases was dyskaryotic, but in five cases, two with agenesis and three left-sided gall bladders were associated with other fetal malformations. In two other cases, the gall bladder appeared dysmorphic on sonographic examination and in both of them intrauterine growth retardation and other anomalies were detected. Trisomy 18 was diagnosed by amniocentesis in one of them. According to our experience, failure to visualize the fetal gall bladder by the 15th gestational week is diagnostic of its absence and should raise the differential diagnosis between gall bladder atresia, which has a good prognosis, and external biliary atresia, which has a poor prognosis. Further experience is needed to characterize the various gall bladder malformations and their prognosis.     

Maternal urinary β-core fragment of hCG/creatinine ratios and fetal chromosomal abnormalities in the second trimester of pregnancy

Our aim was to evaluate the potential value of the ratio of the maternal urinary beta-core fragment of human chorionic gonadotropin (βC-hCG) to creatinine (Cr) in discriminating between normal pregnancies and pregnancies associated with fetal chromosomal abnormalities. We hypothesized that pregnancies with fetal chromosomal abnormalities had abnormal quantities of βC-hCG in the urine. The aims of the present study were to investigate retrospectively whether maternal urinary ratios of βC-hCG/Cr are abnormal in women carrying fetuses with chromosome aberrations and to determine normative median values and a reference range for βC-hCG/Cr between 14 and 19 weeks' gestation. Maternal urinary βC-hCG and Cr concentrations were measured in 150 healthy women from 14 to 19 weeks and compared with ten cases of fetal chromosomal abnormalities matched for gestational age. The preliminary cut-off points corresponded to 0·29 multiple of the normal median (MOM) and 2·83 MOM, which were equivalent to the tenth and 90th centiles of the normal range. Of ten cases of fetal chromosomal abnormalities, one out of one (100 per cent) case with trisomy 18 and three of four (75 per cent) cases of variant 9 chromosome had low βC-hCG/Cr (≤0·29 MOM). One of five (20 per cent) cases with Down syndrome had elevated βC-hCG/Cr (≤2·83 MOM). Urinary βC-hCG/Cr ratios obtained in the second trimester may be useful for improved detection efficiency of Down syndrome, trisomy 18, and inversion of chromosome 9. Second-trimester maternal urinary βC-hCG/Cr should be investigated further as a potential marker for fetal chromosome anomalies.