Prenatal sonographic diagnosis of Malpuech syndrome

Malpuech syndrome (MS) is a rare autosomal recessive syndrome featuring pre- and post-natal growth deficiency, mental retardation, facial dysmorphism, cleft lip and palate (typically midline or bilateral), caudal appendage, renal malformations and male genital abnormalities. A prenatal diagnosis of MS was made in this fetus based on the family history and a combination of conventional and 3D prenatal ultrasound findings. The family were consanguineous with an affected first child. Prenatal ultrasound in the second pregnancy demonstrated bilateral cleft lip and palate in association with intrauterine growth retardation on serial prenatal ultrasound scans. Dysmorphic facial features and a small penis consistent with the diagnosis were confirmed on 3D scanning. Post-natal examination of the neonate confirmed the diagnosis of MS. To the best of our knowledge, this is the first prenatal diagnosis of this syndrome. Copyright © 2006 John Wiley & Sons, Ltd.     

Prenatal diagnosis of inherited metabolic disorders by quantitation of characteristic metabolites in amniotic fluid: Facts and future

An attempt is made to summarize as completely as possible what is known about the prenatal diagnosis of amino– and organic acidurias by direct measurement of characteristic metabolites in amniotic fluid, and to indicate which disorders can potentially be diagnosed prenatally by direct quantitation of metabolites. Furthermore, the disorders are mentioned in which the prenatal diagnosis was proven to be unsuccessful by this approach. The prenatal diagnoses of a case of propionic acidemia and a case of tyrosinemia type I in the 11th and 12th week of gestational age, respectively, are reported and the prospects of performing amniocentesis in the first trimester for prenatal diagnosis are discussed.     

Partial trisomy 20p resulting from recombination of a maternal pericentric inversion: case report of a prenatal diagnosis by chorionic villus sampling

We report a case of prenatal diagnosis of trisomy 20p resulting from a maternal pericentric inversion. The diagnosis was confirmed on both chorionic villi and amniotic cells. This case underlines the fact that prenatal ultrasound diagnosis of this structural anomaly is difficult. The only early sonographic feature was increased nuchal translucency. Copyright © 2006 John Wiley & Sons, Ltd.     

Prenatal diagnosis of familial tuberous sclerosis following detection of cardiac rhabdomyoma by ultrasound

The authors report a case of tuberous sclerosis (TS), diagnosed by prenatal ultrasound, which was suspected by the detection of intracardiac tumours and confirmed by the family investigation. Cardiac rhabdomyomata can be visualized early on echography and must suggest this diagnosis. The place of genetic counselling and prenatal diagnosis in TS is examined.     

Prenatal diagnosis of femur-fibula-ulna complex by ultrasonography in a male fetus at 24 weeks of gestation

We present a case of ultrasonographic prenatal diagnosis at 24 weeks of femur—fibula—ulna (FFU) complex. To our knowledge, this is the first report of an early prenatal diagnosis of FFU.     

Prenatal diagnosis of a new syndrome: Holoprosencephaly with hypokinesia

Markedly decreased fetal activity (akinesia/hypokinesia) is usually readily apparent to experienced mothers, and frequently this concern leads to attempts at prenatal diagnosis. We report prenatal diagnosis of two fetuses with congenital contractures, markedly decreased fetal movement, and microcephaly due to severe holoprosencephaly. Such familial recurrence to phenotypically normal parents suggests a newly recognized autosomal recessive or X-linked syndrome that is readily detectable by prenatal ultrasonography.     

Prenatal screening for haemoglobin disorders

The technology has been available to detect carriers of haemoglobin disorders since the late 1960s. Prenatal diagnosis has been available since 1978. First trimester diagnosis by chorionic villus sampling and DNA analysis was introduced in 1982, and subsequent simplifications in DNA technology have made screening, counselling and prenatal diagnosis cost-effective at the community level, in countries at all levels of development. Audit of prenatal diagnosis for haemoglobin disorders in countries which have the resources and infrastructure necessary for genetic population screening (such as the UK and other European countries), has shown that the number of prenatal diagnoses actually performed fall far short of expectation. The demonstration that this reflects failures in delivering information, screening and counselling to the populations at risk, rather than rejection of prenatal diagnosis, shows the importance of placing more emphasis on the organisational and social requirements for genetic population screening. In some countries current attitudes towards abortion exclude provision of prenatal diagnosis within the health service, but in many such cases it has been set up in the private sector. It is also being introduced through combined private and charitable efforts in an increasing number of developing countries, including some with extremely limited health resources: such centres are likely to act as nuclei for emergence of genetics services in these communities. A particularly notable recent achievement is the introduction of prenatal diagnosis in Nigeria, where 1–2% of all children born suffer from sickling disorders.     

Prenatal diagnosis of trisomy 21 and X/XX sex chromosome mosaicism

Double aneuploidy involving Down syndrome and Turner syndrome is a rare chromosomal abnormality presumed to occur with a frequency of about 1 in 2 million births. Twenty-one cases of this combined anomaly have been reported and two infants were born with this anomaly after a mistake in prenatal diagnosis. We report the first prenatal diagnosis of Down syndrome combined with Turner mosaicism and suggest that this polysyndrome may be more common than previously estimated. We, therefore, wish to alert cytogenetic laboratories performing prenatal diagnoses of the potential risks of misdiagnosis of this polysyndrome if banding is not performed and if a sufficient number of mitotic cells are not analysed.     

DNA-based carrier detection and prenatal diagnosis of tyrosinase-negative oculocutaneous albinism (OCA1A)

We describe molecular prenatal diagnosis and carrier detection of tyrosinase-negative oculocutaneous albinism (OCA1A) in two families. In one family, we carried out DNA-based prenatal diagnosis of OCA1A. In the other family, mutation analysis and carrier detection obviated the need for prenatal diagnosis. Molecular analysis is safer and probably more accurate than fetoscopy and fetal scalp biopsy, and should become the method of first choice for prenatal diagnosis of OCA1.     

Measurement of the fetal mandible—feasibility and construction of a centile chart

The prenatal diagnosis of micrognathia is usually based on a subjective impression of the size of the jaw when examining the fetal profile. We have constructed a centile chart for mandibular length between 12 and 27 post-menstrual weeks in a cross-sectional study of 184 fetuses. The application of this chart in clinical practice may permit a more objective diagnosis of micrognathia in the prenatal period.     

Prenatal diagnosis of pyruvate dehydrogenase E1α subunit deficiency

Pyruvate dehydrogenase (PDH) E1α subunit deficiency is an X-linked inborn error of metabolism affecting males and females with equal frequency. The diagnosis is usually based on determination of enzyme activity, although this may present difficulties in some females because of X-inactivation patterns favouring expression of the normal X chromosome. This is a particular problem for prenatal diagnosis using chorionic villus cells where normal enzyme assay results do not necessarily exclude the diagnosis and confirmatory X-inactivation analysis may be complicated by variable methylation of active and inactive X chromosomes. We describe prenatal diagnosis in two pregnancies in a family following diagnosis of a PDH E1α deficient male. The first prenatal diagnosis was performed by enzyme assay, but by the time of the subsequent pregnancy, the underlying mutation in the affected male had been identified and direct gene analysis was possible. This study highlights the limitations of diagnosis of PDH E1α deficiency based on measurement of the gene product and illustrates the need for mutation analysis in affected individuals.     

Prenatal diagnosis in advanced maternal age. Amniocentesis or CVS,a patient's choice or lack of information?

Ninety-six women of advanced maternal age were interviewed about the way they obtained information on prenatal diagnosis and about how the decision was made as to what procedure was to be performed (transabdominal chorionic villus sampling (TA-CVS) or amnio-centesis). In the CVS group, women visited their physician or midwife earlier in pregnancy (mean 7.1 weeks) than those in the amniocentesis group (mean 10.7 weeks). The availability of prenatal diagnosis was not mentioned during the first antenatal visit in 55 per cent of women from the amniocentesis group as opposed to 25 per cent from the TA-CVS group. Approximately 40 per cent of women eligible for prenatal diagnosis did not receive any information from the referring body prior to counselling at our centre. Only 29 per cent of women who underwent amniocentesis had actually chosen this procedure; 71 per cent were too late to undergo TA-CVS at 12 weeks. It is concluded that information to the patient must be improved in order to ensure early referral for prenatal diagnosis.     

Rapid prenatal diagnosis of Duchenne muscular dystrophy with gene duplications by ion-pair reversed-phase high-performance liquid chromatography coupled with competitive multiplex polymerase chain reaction strategy

Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are caused by various mutations in the dystrophin gene. Rapid prenatal diagnosis of DMD with gene duplications is difficult due to limitation in gene dosage determination and the requirement for a known disease-causing mutation in the pedigree to achieve a rapid and accurate diagnosis. We report, here, a case with rapid prenatal diagnosis of DMD-affected male with gene duplications in the absence of a known disease-causing variation in the pedigree by using ion-pair reversed-phase high-performance liquid chromatography (IP-RP-HPLC) coupled with competitive multiplex polymerase chain reaction (PCR) protocol. In cases with clinical diagnosis of DMD/BMD, this test should identify greater than 92% of disease-causing DNA variants. The postnatal genetic diagnosis of this case and the same disease-causing mutations subsequently identified in other members of the pedigree confirmed the accuracy of competitive multiplex PCR/IP-RP-HPLC assay in direct prenatal diagnosis of DMD. Copyright © 2007 John Wiley & Sons, Ltd.     

Women's opinions on the offer and use of prenatal diagnosis

We have studied the opinions and attitudes of women towards prenatal diagnosis (amnio-centesis/chorionic villus sampling/ultrasound/serum AFP testing). A questionnaire was sent to 185 women who had had their first baby a few months before. The respondents have a strong positive attitude towards the diagnostic procedures, especially if treatable abnormalities can be detected. Younger women and women with a high level of education were less inclined to make use of prenatal diagnosis. If tests were made more widely available, this might lead to a significant increase in the use of prenatal diagnosis.     

Prenatal molecular diagnosis in hypertrophic cardiomyopathy: report of the first case

Hypertrophic cardiomyopathy (HCM) is an autosomal dominant disease that may cause premature sudden death, especially in teenagers and young adults. The recent progress in the molecular genetics of the disease has made genetic testing sometimes available in clinical practice. We report the case of a couple who still requested prenatal molecular testing after detailed information had been given through a multidisciplinary consultation. Prenatal diagnosis in HCM is associated with complex medical and psychological implications, in addition to general ethical considerations, as the potential value of the diagnosis is counterbalanced by the highly variable expression of the disease and the difficulty in predicting its evolution. The R403L mutation in the MYH7 gene had been previously identified in this family, characterized by a malignant form of HCM. In the specific context of this case, we decided to agree to the request of the parents and performed the prenatal diagnosis. To the best of our knowledge, this is the first report of a prenatal molecular diagnosis performed in the context of HCM. Copyright © 2004 John Wiley & Sons, Ltd.     

Prenatal diagnosis of a de novo complex chromosomal rearrangement involving four chromosomes

A complex chromosome rearrangement, apparently a balanced translocation involving chromosomes 4,6, 15 and 16, was found in cultured cells of amniotic fluid from a 32–year-old primigravida who requested amniocentesis for prenatal diagnosis because of a family history of mental retardation. Chromosome analysis of peripheral blood from both parents were normal. The couple was counselled for the prenatal diagnosis of this de novo complex translocation and, subsequently, elected to terminate the pregnancy. Post-mortem examination revealed a 23–week fetus with intrauterine growth retardation. The identical chromosome rearrangement was subsequently confirmed in cultured fibroblasts from skin and cord obtained from the abortus. To our knowledge, this is the first report where routine prenatal diagnosis revealed a fetus with a balanced complex chromosomal rearrangement involving four chromosomes of de novo origin.     

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 of propionic acidemia

In this report we summarize our experience in prenatal diagnosis of propionic acidemia (PA) since 1987. Overall, we have investigated 25 pregnancies at risk from 19 unrelated families. Until genetic structure of the genes involved in PA was elucidated, prenatal diagnosis has been successfully performed by means of metabolite quantitation and/or enzymatic assays in foetal issue. Today, direct propionyl-CoA carboxylase activity assay in combination with molecular analysis in chorion villi can be regarded as a fast and reliable method of choice for prenatal diagnosis of this organic acidemia. Copyright © 2004 John Wiley & Sons, Ltd.     

First-trimester diagnosis of conjoined twins

Conjoined twins are a rare and complex complication of monozygotic twinning, which is associated with high perinatal mortality. Early prenatal diagnosis of conjoined twins allows better counselling of the parents regarding the management options, including continuation of pregnancy with post-natal surgery, termination of pregnancy or selective fetocide in case of a triplet pregnancy. With the introduction of high-resolution and transvaginal ultrasound imaging, accurate prenatal diagnosis of conjoined twins is possible early in pregnancy. We have reviewed the medical literature on the early prenatal diagnosis of suspected conjoined twins using a MEDLINE search. Although first-trimester diagnosis of conjoined twins is feasible, false-positive cases are common before 10 weeks because, earlier in gestation, fetal movements are limited and monoamniotic twins may appear conjoined. As most parents opt for immediate termination of pregnancy at confirmation of the diagnosis, there are limited data on the prenatal follow-up of conjoined twins. When the parents opt for conservative management, half of the fetuses die in utero and another 44% will die during the neonatal period. A detailed analysis of case reports where 3D imaging was used indicates that this modality does not improve on the diagnosis made by 2D ultrasound. Overall, very early prenatal diagnosis and first-trimester 3D imaging provide very little additional practical medical information compared to the 11–14 weeks' ultrasound examination. Copyright © 2005 John Wiley & Sons, Ltd.     

Prenatal diagnosis of an intra-abdominal sacrococcygeal teratoma

The prenatal diagnosis of a presacral (type IV) sacrococcygeal teratoma (SCT) is described. The initial ultrasound appearance was suggestive of a lower urinary tract obstruction, but further ultrasonic examination and radiological imaging using contrast medium led to the diagnosis of SCT. This is the first prenatal diagnosis of a totally intra-abdominal SCT.