Unexpected ultrasonographic prenatal diagnosis of autosomal dominant polycystic kidney disease

The prenatal diagnosis of autosomal dominant polycystic kidney disease (ADPKD) is now being reported with increasing frequency. We report three cases and review 12 cases of ADPKD diagnosed in the fetus by ultrasonographic findings. Increased echogenicity and renal enlargement are the main ultrasonographic signs of ADPKD. Renal cysts are uncommon. Diagnosis is easy in a family with a positive ADPKD history. Conversely, there may be no apparent family history, as in our three cases and three cases from the literature. We consider the problems of unexpected diagnosis, family investigation, and the prognosis of ADPKD in children with prenatally diagnosable forms.     

Early prenatal diagnosis of genetic microcephaly

We report a new case of prenatal diagnosis of recessive microcephaly by ultrasound examination allowing termination of pregnancy at 25 weeks gestation.     

Autosomal dominant polycystic kidney disease: Prenatal diagnosis by DNA analysis and sonography at 14 weeks

A pregnant woman affected with autosomal dominant polycystic kidney disease (ADPKD) had a history of an affected fetus, diagnosed by sonography at 29 weeks of pregnancy. The proband's father was also affected. DNA analysis performed on chorionic villi at 11 weeks during a second pregnancy predicted an affected fetus, and sonographic examination at 14 weeks confirmed the diagnosis.     

Prenatal diagnosis of autosomal dominant polycystic kidney disease using flanking DNA markers and the polymerase chain reaction

A prenatal diagnosis was carried out on a 9-week-old fetus at risk for autosomal dominant polycystic kidney disease (ADPKD). Ten members of the family were previously typed using five DNA markers linked to the PKD1 locus on chromosome 16, and one marker linked to the putative PKD2 locus on chromosome 2. The polymerase chain reaction (PCR) was used to amplify the D16S125 locus. Pairwise and multipoint lod scores indicated that the family was most likely segregating a PKD1 mutation. The fetus inherited the disease haplotype from the affected parent. Diagnostic accuracy was greater than 99 per cent, taking into account the possibility of genetic heterogeneity.     

Clues and pitfalls in the early prenatal diagnosis of ‘late onset’ infantile polycystic kidney

Infantile polycystic kidney disease (IPKD) is an autosornal recesive inherited disorder, IPKD has been previously diagnosed by us as early as the 14th week of gestation. ‘Late onset’ (third trimester) IPKD has been previously described by several authors. We present here a case of intrauterine detection of ‘late onset’ IPKD, suggesting that elongated hyperechogenic kidneys (with normal transverse and anteroposterior diameters) should be considered as an early sign of ‘late onset’ presenting IPKD.     

Prenatal diagnosis of adult polycystic kidney disease with DNA markers on chromosome 16 and the genetic heterogeneity problem

A prenatal diagnosis of adult polycystic kidney disease by DNA testing is reported. Evidence showing a linkage between the disease and the 3′HVR and 24.1 restriction fragment length polymorphisms (RFLPs) on chromosome 16 was obtained in the proband's family by linkage analysis of data and homogeneity testing with Italian families of the linked type. Fetal genotype prediction based on both flanking markers was confirmed by histological and ultrastructural findings in fetal kidneys.     

Diastrophic dysplasia: A specific prenatal diagnosis by ultrasound

In a pregnant woman without increased genetic risk, the presence of distrophic dysplasia of the fetus was diagnosed sonographically at 31 weeks' gestation and definitively distinguished from other skeletal dysplasias. In all prenatal diagnoses of diastrophic dysplasia reported so far, this autosomal recessive congenital condition had occurred in the family's previous children and this made the diagnoses of fetal diastrophic dysplasia easier. The reported case was diagnosed due to evidence of an extreme shortening of all long bones of the extremities associated with other skeletal deformities which, taken as a whole, are typical of this syndrome: micrognathia, cervical kyphosis, persistent extension limitation in elbow and knee joints, club feet, ulnar diviation of hands, shortened phalanges, and, in particular, abduction of thumbs (‘hitchhiker thumbs’) and big toes.     

Short communications prenatal detection of the autosomal recessive type of polycystic kidney disease by trehalase assay in amniotic fluid

We report relatively high trehalase activity in amniotic fluid of a fetus affected with the autosomal recessive type of polycystic kidney disease (type II), suggesting that prenatal detection of this condition could be done on this basis in conjunction with ultrasonography.     

Prenatal diagnosis of autosomal recessive osteopetrosis,infantile type,by X-ray evaluation

Prenatal diagnosis for infantile osteopetrosis was attempted during the third pregnancy of a first-cousin marriage whose family history revealed an affected previous child. At the 25th week of pregnancy, fetal X-ray evaluation revealed marked sclerosis of osteopetrotic bone and metaphyseal splaying and clubbing of both femurs. The pregnancy was terminated and repeated X-rays and histopathological examination of fetal bone (femur) confirmed the diagnosis.     

Prenatal diagnosis and obstetrical management of multicystic dysplastic kidney disease

Multicystic dysplastic kidney disease (MDKD) is one of the most common congenital renal anomalies. We report 16 consecutive cases of MDKD recognized in the antenatal period by sonography. Diagnosis is usually easy as MDKD has in the vast majority of cases a striking ultrasound appearance including enlargement of the kidney and multiple renal cysts. However, differentiation from obstructive uropathy may be difficult, and we made a total of five erroneous diagnoses. Unilateral MDKD has almost invariably a good prognosis. However, severe life-threatening associated anomalies were found in six cases. Therefore, a detailed survey of fetal anatomy and determination of karyotype are strongly recommended.     

Prenatal diagnosis of pelvic kidney

A 30-year-old woman had serial ultrasound scans from 28 weeks' gestation which revealed the presence of a cystic area in the fetal pelvis. The ‘cyst’ remained unchanged until delivery at 41 weeks. Fetal growth and amniotic fluid volume were normal throughout. A pelvic kidney was confirmed at birth. The differential diagnosis and antenatal management of this ‘cyst’ are discussed.     

Prenatal ultrasound diagnosis of Apert's syndrome

A mother affected with Apert's syndrome was diagnosed by ultrasound scan at 16–17 weeks to have a fetus similarly affected. The typical features of acrocephaly and symmetrical syndactyly were seen. This is probably the first time that this condition has been diagnosed at such a gestation by ultrasound scan. The patient decided to continue the pregnancy, and intrauterine death occurred at 34 weeks. The diagnosis was confirmed by pathological examination.     

Carrier detection and prenatal diagnosis in Norrie disease

We report the use of DNA probes to determine carrier status in three young women from a large kindred with Norrie disease. One of the women requested prenatal diagnosis during pregnancy. In this pedigree, Norrie disease was not characterized by a deletion at DXS7.     

Physicians' acceptability of termination of pregnancy after prenatal diagnosis in southern france

The acceptability of prenatal diagnosis for Down's syndrome has been extensively studied over the last 15 years but that of other pathologies remains largely unexplored. The main goals of this study were to approach physicians' opinions on six reasons for termination of pregnancy showing different deficiencies, i.e., Down's, Turner and Klinefelter syndromes, cystic fibrosis, spina bifida, and haemophilia, and to identify the origins of reserves. The influence of sociodemographic and professional characteristics of physicians on their opinions and attitudes during the consultation were studied. The data presented are based on information gathered in 1985 by a mailed questionnaire answered by 853 general practitioners, gynaecologists, obstetricians, and pediatricians in the Marseilles Genetic Centre's region. Stepwise logistic regression was used for the multivariate analysis. The results showed that 78 per cent of those answering favour termination of pregnancy for Down's syndrome and that only moral reticences were mentioned by the physicians opposed. Conversely, for haemophilia, only 21 per cent of the physicians considered this indication justified; those opposed were for the most part concerned that severity of illness did not justify termination of pregnancy. Overall, 33 per cent of physicians would voice their personal opinion on termination of pregnancy if so requested by consultees. Results on the influence of age and specialty evidenced their role on physicians' opinions. Indeed, 30 per cent of physicians opposed to pregnancy termination for one of the six fetal anomalies retained herein would modify their positions if diagnosis were possible in the first trimester of pregnancy.     

Experience with first trimester prenatal diagnosis of Menkes disease

We have performed 28 first trimester diagnoses for Menkes disease in 27 high risk pregnancies by direct copper measurement on chorionic villi (c.v.) Two male fetuses were found to be affected because of significantly increased copper content. In one male fetus a slightly increased copper content was observed indicating an exogenous copper contamination of the sample. This view was supported by normal results observed after abortion. Three out of 15 diagnostic c.v. samples with a female karyotype showed increased copper levels. In two of these cases, part of the copper content might have been released from the cannulae used for these particular biopsies. Histochemical visualization of copper accumulation in fixed chorionic villi of two affected fetuses and one female fetus was observed. [⁶⁴Cu]-uptake studies have been performed on 11 diagnostic and 10 control c.v. samples. As the control samples in some cases were found to incorporate more [⁶⁴Cu] than the corresponding diagnostic sample, this method cannot at present be used for diagnosis. Compiled results on newborn females gave evidence that two carriers expressed the paternal X-chromosome, and two carriers expressed the maternal X-chromosome in chorionic villi.     

Evaluation of prenatal diagnosis of congenital heart disease

Prenatal diagnosis performed by fetal ultrasound scan is now a routine part of antenatal care in many countries. That an increasing number of fetal anomalies may be detected on prenatal ultrasound is beyond doubt. What is possible is not, however, always practical, especially when congenital heart diseases (CHDs) are concerned and when whole antenatal populations are screened rather than high-risk groups. Thanks to our registry of congenital anomalies, a retrospective study was undertaken to evaluate the prenatal detection of CHDs by ultrasound scan in 131 760 consecutive pregnancies of known outcome from 1979 to 1988. Only 84 out of 912 malformed fetuses with CHDs without chromosomal anomalies were detected (9.2 per cent). The sensitivity of detection varied from around 38 per cent for malformations such as hypoplastic left heart and single ventricle to around 5 per cent for ventricular and atrial septal defects. The effectiveness of the detection of some forms of major congenital heart disease has increased dramatically since 1987 by including routine examination of the four-chamber view and of the inflow and outflow tracts of the fetal heart. Our results stress the need to obtain a definite clear four-chamber view, to perform scans at ⩾ 18 weeks of gestation, and to train sonographers in order to improve the prenatal detection of CHDs.     

Lobar holoprosencephaly: prenatal MR diagnosis with postnatal MR correlation

Holoprosencephaly is a congenital anomaly characterized by lack of cleavage of the prosencephalon. Although, relatively rare, it is the most common anomaly that involves both the brain and the face. Prenatal diagnosis of this anomaly using ultrasonography, particularly of the less severe forms, is difficult. Magnetic resonance imaging has recently become an important complement to US in prenatal diagnosis of CNS anomalies. We herein report a patient in whom, at 23 weeks of gestation, US suggested agenesis of the corpus callosum and in whom, at 24 weeks of gestation, MRI correctly diagnosed lobar holoprosencephaly, which was confirmed by a postnatal MRI at 3 weeks of age. Copyright © 2005 John Wiley & Sons, Ltd.     

The impact of prenatal diagnosis on the occurrence of chromosome abnormalities

From the public health point of view, several formal attempts have been made to measure the impact of prenatal diagnosis (PND) on the incidence of Down's Syndrome (DS), but the results have varied widely. The impact of PND (reduction in the birth rate of chromosomally abnormal neonates) is related to utilization rates but quantitative estimates of this have not been established. In a three-year (1981–1983) total population study from Queensland, Australia, we present results to measure the impact of a voluntary PND programme on the birth incidence of DS, and also other chromosomally abnormal births. Utilization rates for the PND service were 15·5 per cent in that population of mothers 35 years and over. Numbers and rates of all cases of chromosomal abnormalities are presented, subclassified by type of diagnosis–-either by PND or by clinical diagnosis after birth. For the total population, 7·3 per cent of cases of DS were detected prenatally, and 15·4 per cent of all chromosome abnormalities. (A method for measuring the impact of PND is described.) Using this in conjunction with our demographic data, we estimate that with a 15 per cent utilization rate of PND by older mothers, 14 per cent of DS births can be prevented in this age group, or a 5 per cent overall reduction can be achieved if mothers of all ages are considered. One index–-the ratio of the percentage of DS births which are preventable compared with the population utilization rates of PND–-has potential for widespread use. Queensland data for this ratio is 0·34, a figure consistent with that from other studies. Thus a 3·5 per cent drop in the overall DS birth rate may be expected for each 10 per cent increase in the utilization rates of PND for mothers of 35 years and over. A diagram is presented which may serve as a model for improved data collection and better impact estimates in the future.