Screening for trisomy 21 in twin pregnancies in the first trimester: does chorionicity impact on maternal serum free β-hCG or PAPP-A levels?

In a study of 180 twin pregnancies I have examined the distribution of maternal serum free β-human chorionic gonadotrophin (β-hCG) and pregnancy-associated plasma protein-A (PAPP-A), in addition to fetal nuchal translucency thickness (NT), in twins classified as monochorionic or dichorionic, based on ultrasound appearance at 10–14 weeks of gestation. In 45 monochorionic and 135 dichorionic twin pregnancies the median MoM free β-hCG was not significantly different (1.00 vs 1.01), whilst that for PAPP-A was lower (0.89 vs 1.01) but again with no statistical significance. Previous reports of an increased fetal NT in monochorionic twins pregnancies could not be confirmed (1.03 vs 1.00). It is concluded that the existing pseudo risk twin correction algorithm is appropriate for both monochorionic and dichorionic twins in providing accurate first trimester risks for trisomy 21. Copyright © 2001 John Wiley & Sons, Ltd.     

Mesomelic campomelia,polydactyly and Dandy–Walker cyst in siblings

The present report describes two fetuses, one female and one male, with thus far undescribed skeletal malformations. The mother was a gravida 2, para 0. Both pregnancies were terminated in the second trimester because of multiple congenital anomalies diagnosed ultrasonographically resembling a short rib-polydactyly syndrome. Both fetuses were found to have postaxial hexadactyly of the hands and feet, marked bilateral campomelia of the forearm and shank bones, and a Dandy–Walker cyst. In addition, the fourth ventricle was dilated in the first sibling and the second sibling had an inverse intestinal malrotation. A literature search failed to reveal similar observations. Copyright © 2001 John Wiley & Sons, Ltd.     

Maternal serum levels of total activin-A in first-trimester trisomy 21 pregnancies

Maternal serum total activin-A concentration was measured in 45 pregnancies affected by trisomy 21 and 493 control unaffected pregnancies at 10–14 weeks of gestation. In the trisomy 21 pregnancies total activin-A concentration was significantly higher (1.36 MoM of the unaffected pregnancies) and in 16% of cases the level was above the 95th centile of normal. The log₁₀ SD for the control group and the trisomy 21 group were 0.17 and 0.22, respectively. The median pregnancy associated plasma protein-A (PAPP-A) in this trisomy 21 series was 0.49 and for free β-hCG was 2.05. In the trisomy group there were significant positive associations between total activin-A and PAPP-A (0.6071) and free β-hCG (0.4255). The low median difference and the high overlap in values between trisomic and unaffected pregnancies make total activin-A of little practical use in first-trimester screening for trisomy 21. Copyright © 2001 John Wiley & Sons, Ltd.     

Split notochord syndrome — prenatal ultrasonographic diagnosis

Split notochord syndrome is a rare condition that is characterized by a persistent connection of the gut and dorsal skin of the back, an enteric cyst and vertebral anomalies. We present two cases in which prenatal ultrasound showed polyhydramnios. In one case it was associated with vertebral abnormalities and a right-sided mediastinal cyst found to be the stomach. Postnatal evaluation confirmed the diagnosis of split notochord syndrome. The association of sonographic findings of hydramnios, thoracic cysts and vertebral anomalies suggests prenatal diagnosis of split notochord syndrome. Copyright © 2001 John Wiley & Sons, Ltd.     

Klippel–Trenaunay–Weber (KTW) syndrome: the use of in utero magnetic resonance imaging (MRI) in a prospective diagnosis

The diagnosis of the Klippel–Trenaunay–Weber (KTW) syndrome is rarely made antenatally. We report the use of both ultrasound and in utero magnetic resonance imaging (MRI) in the prenatal diagnosis of this syndrome. This is the first report of the use of prenatal MRI in the diagnosis of this condition. There was concordance in the findings of both modalities, with limb hypertrophy, and multiple haemangiomata – both subcutaneous and internally – demonstrated with ultrasound and MRI. The patient elected to terminate the pregnancy because of associated oligohydramnios and a small fetal chest noted at 20 weeks. The postmortem examination confirmed the antenatal diagnosis. Copyright © 2001 John Wiley & Sons, Ltd.     

Prenatal diagnosis: does it alter outcome?

The prenatal detection of urinary tract anomalies is changing paediatric practice but in many areas the impact on clinical outcome remains difficult to quantify. However it is already apparent that termination of pregnancy has reduced the numbers of infants with lethal pulmonary hypoplasia and renal dsyplasia who would previously have been liveborn but destined to succumb as neonates. Similarly, referrals of major non lethal abnormalities such as bladder exstrophy are declining as parents increasingly opt for termination. Fetuses at greatest risk of early onset postnatal renal failure can now be identified with considerable accuracy on prenatal ultrasound. Termination, prompted by quality of life considerations, could result in reduced numbers of infants and young children requiring end stage renal failure treatment in the first few years of life. Pre natal detection of anomalies such as PUJ obstruction and reflux undoubtedly provides an opportunity to avert functional deterioration and minimise urinary infection. But the proportion of children who genuinely benefit has proved difficult to assess. The prenatal detection of mild dilatation is of doubtful benefit in all but a minority of cases. Clinically significant underlying pathology is rare yet this common prenatal finding often generates disproportionate parental anxiety. Copyright © 2001 John Wiley & Sons, Ltd.     

Prenatal diagnosis in Coffin-Lowry syndrome demonstrates germinal mosaicism confirmed by mutation analysis

Coffin-Lowry syndrome is a rare X-linked, semi-dominant mental retardation syndrome resulting from mutations of the ribosomal S6 kinase 2 (RSK2) gene. In the present report, a male patient affected with Coffin-Lowry syndrome is shown to have a nonsense mutation of the RSK2 gene. His unaffected mother does not have this mutation in her lymphocytes. In her third pregnancy prenatal diagnosis by mutation analysis has detected gonadal mosaicism. As this is the second report of germinal mosaicism in Coffin-Lowry syndrome, the finding has important implication for genetic counselling. Copyright © 2001 John Wiley & Sons, Ltd.     

Prenatal diagnosis of hunter syndrome

Sixteen pregnancies at risk for Hunter syndrome have been monitored by amniocentesis. Iduronate 2-sulphate sulphatase levels were measured in amniotic fluid, cultured amniotic fluid cells and cord blood. Thirteen of the pregnancies resulted in normal livebirths, two are continuing and one affected pregnancy was terminated. Reduced enzyme levels were observed in either amniotic fluid, cells or cord blood for four female fetuses. Such fetuses are likely to be carriers expressing reduced enzyme levels. The affected male fetus had reduced enzyme activity in amniotic fluid; insufficient cells were cultured for enzyme estimation, however no enzyme activity was detected in fetal liver after termination. Eight cord blood enzyme estimations have been performed, five confirming normal male infants.