Adult-onset GM2 gangliosidosis diagnosed in a fetus

Amniocentesis and subsequent tests are reported on a fetus conceived of a rare mating type: its mother has an intermediate level of β hexosaminidase A (HEX A), characteristic of carriers of Tay-Sachs disease (TSD), while the father suffers from an adult-onset GM₂ ganglio-sidosis (AOG) with severe HEX A deficiency. Activity of HEX A in the cultured fetal cells was very low when measured by the heat-inactivation method, thus showing the typical biochemical phenotype of TSD fetuses. However, upon separation of HEX isozymes by ion exchange chromatography, residual HEX A (17 per cent of total HEX) was demonstrated. Also in contrast to TSD fetuses, this fetus' fibroblasts were able to synthesize the precursor of a chains of HEX, and ultrastructural examination of its brain revealed few atypical lamellar bodies, unlike those found in TSD fetuses of the same gestational age. It is therefore concluded that the fetus was not affected with TSD, but rather with AOG.     

Prenatal diagnosis of alpha-1-antitrypsin deficiency by fetal blood sampling

Fetal blood sampling for the diagnosis of alpha-1-antitrypsin deficiency using protein isoelectric focusing was carried out in the period 1980–1985. The results of 25 cases from 18 mothers are reported. All had a previous history of a PiZ child affected by liver disease. The method was found to be technically satisfactory and the fetal results were subsequently confirmed in all 18 cases where follow-up was possible. The fetus was found to be PiZ in nine cases and all these pregnancies were terminated. Of the remaining pregnancies three cases aborted or were delivered prematurely and 13 proceeded to term without complications.     

Prenatal diagnosis of exencephaly

This paper presents a sonographic diagnosis of exencephaly made during the last trimester of gestation. The sonogram showed the absence of bones in the cranial vault together with the presence of a disorganized cerebral mass, with loss of its normal anatomy. Post-partum examination of the newborn confirmed the findings of the sonogram. We briefly review the characteristics of exencephaly, its aetiology, and its relationship to anencephaly.     

Prenatal diagnosis of PIBIDS

In a well-documented PIBIDS family, two investigations of DNA excision repair showed a severe defect in lymphocytes from the index case (residual repair activities were 10.6–12.1 per cent). The values for the mother, father, and sister were within the normal range when compared with a healthy control. In the pregnant mother, a prenatal diagnosis of PIBIDS was made by measuring UV-induced unscheduled DNA synthesis in cultivated amniotic fluid cells. Results ranged between 12.5 and 26.1 per cent depending on the UV doses applied and were consistent with an affected fetus. The parents opted for a termination of pregnancy. Following a therapeutic abortion, fetal skin fibroblasts were tested and showed a severe DNA excision-repair defect of 9.2–13.5 per cent of residual activity.     

Prenatal diagnosis of hypochondroplasia

Prenatal diagnosis of a fetus at risk for hypochondroplasia, a short limb dwarfism condition similar to achondroplasia, was performed by ultrasound at 22 weeks' gestation. The limb bones were measured and shown to be decreased in length. The pregnancy was terminated. Post abortion X-ray did not show caudal narrowing in the lumbar spine but the pelvis had the features of hypochondroplasia.     

Prenatal diagnosis of tetrasomy 21

Amniocentesis and prenatal diagnosis were done for late maternal age and an abnormality consistent with Tetrasomy 21 (47,XX,+t(21;21)) was found in every cell examined of the initial amniotic fluid. Clinical examination revealed a fetus with many of the signs of Down Syndrome and pathological examination revealed gross abnormalities of the internal structures. Follow-up tissues showed mosaic Tetrasomy 21.     

Prenatal diagnosis of chromosome mosaicism

The frequency of mosaicism and pseudomosaicism in the prenatal diagnosis of cytogenetic disorders is reported, based on 3000 pregnancies studied in our laboratory. Diagnosis of true mosaicism was only made when an abnomality was detected in two or more independent cultures established from an amniotic fluid sample. On this basis, 0.37 per cent of all cases were diagnosed as true mosaics. 1.07 per cent of all cases had pseudomosaicism involving more than one cell from the same culture with an identical abnormality. 4.13 per cent of cases had a single abnormal cell with an extra chromosome, loss of a sex chromosome (or part of a sex chromosome), or translocation. Details of the outcome and follow-up of cases is given. Particularly problematical were cases where multiple cells from one culture contained an abnormality which could have been clinically significant. A crude estimate of the extent to which true mosaicism might currently be misinterpreted as pseudomosaicism or entirely missed has been made, based on data from the U.S. survey (Hsu and Perlis, in press). It was concluded that even when two, and if necessary a third culture is extensively analysed with an average of 24 cells per culture counted, at least 4.5 per cent of cases of true mosaicism may be completely missed and at least 7 per cent could be misdiagnosed as pseudomosaicism. There is an urgent need for improved laboratory techniques which allow growth of a greater number of cell colonies and therefore a more broadly based analysis. Detailed long term follow-up of prenatally diagnosed mosaics is also essential for assessing the clinical significance of the laboratory findings.     

Prenatal diagnosis of genetic microcephaly

True microcephaly can be diagnosed at an early stage of gestation by serial measurements of fetal head growth as demonstrated by this case report in which the diagnosis of genetic microcephaly was made but termination refused. True microcephaly was evident at birth.     

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 diagnosis of dyssegmental dwarfism

Fetal ultrasound evaluations at 18 weeks gestation on two consecutive pregnancies of a woman who previously gave birth to a stillborn female affected with dyssegmental dwarfism, resulted in accurate diagnoses of unaffected and affected fetuses. Marked disorganization of vertebral bodies and associated encephalocele found in two affected cases in this family are consistent with the original observation of this new syndrome as two major aspects which differentiate it from other forms of lethal dwarfism.     

Prenatal diagnosis of mandibulofacial dysostosis

Four fetuses at risk of the autosomal dominant Treacher—Collins syndrome were examined by fetoscopy in the second trimester of pregnancy. Findings were normal in two cases and healthy babies were delivered after uneventful pregnancies. Mandibular hypoplasia and abnormalities of the palpebra and auricles were seen in the other two fetuses; one had an associated cleft palate. These pregnancies were terminated and the diagnoses confirmed by post-mortem examination.     

Prenatal diagnosis of mosaic trisomy 9

Mosaic trisomy 9 was detected in an amniotic fluid cell culture from a 40-year-old woman evaluated because of advanced maternal age. After counselling, parents elected to terminate the pregnancy. On autopsy the fetus was found to have hydrocephalus and a single kidney. The diagnosis of trisomy 9 mosaicism was confirmed in cultured skin fibroblasts. This is the third reported case of trisomy 9 mosaicism diagnosed prenatally.     

Prenatal diagnosis of intrapericardial teratoma

A case of intrapericardial teratoma diagnosed by ultrasound before birth is described. Planning for delivery and immediate neonatal intensive management allowed successful cardiac surgery, full resection of the tumour and full recovery.     

Prenatal diagnosis of pyruvate carboxylase deficiency

Prenatal diagnosis of pyruvate carboxylase (PC) deficiency was performed in a family at risk for the acute neonatal form of this disease which manifests secondary citrullinemia. The diagnosis of an affected child was confirmed by enzyme assay and ³H-biotin labelling of proteins in cultured fetal skin fibroblasts. Sufficient amniocytes were cultured in 3–4 weeks for enzyme analysis in two centres. Citrulline concentration in amniotic fluid (AF) was normal in the affected fetus.     

Prenatal diagnosis of the pterygium syndrome

We report two second trimester pregnancy terminations in the same woman following intrauterine ultrasonic findings of hydrops fetalis, polyhydramnios, lack of fetal movements, and short, fixed malformed limbs. One fetus also showed a cystic mass at the back of the head. Radiographic and anatomic studies of the fetuses demonstrated multiple pterygia, flexion contracture of multiple joints, abnormal facial appearance, cleft palate, pulmonary hypoplasia, and gracile bones. The cystic mass of the back of the head was found to be a cystic hygroma. These findings are consistent with the lethal variant of multiple pterygium syndrome. Early prenatal diagnosis of this condition is possible using ultrasonography.     

Prenatal diagnosis of syndromes associating albinism and immune deficiencies (Chediak-Higashi syndrome and variant)

We have successfully undertaken the prenatal diagnosis of two hereditary syndromes associating albinism and immune defects. Because the genes responsible for these diseases have not yet been mapped and the immune abnormalities are too subtle to be diagnosed in utero, the prenatal diagnosis was made using a morphological approach. In the case of Chediak-Higashi syndrome, it was based on light microscopic examination of the hair shaft and on light and electron microscopic study of polymorphonuclear cells. In the syndrome associating immune deficiency and partial albinism, the Griscelli syndrome, only examination of the hair was feasible. The diagnosis was negative in 12 fetuses at risk and positive in four.     

Prenatal diagnosis of severe osteogenesis imperfecta

The ultrasound findings in a series of 15 prenatally diagnosed cases of severe osteogenesis imperfecta types IIA, IIB, IIC, and III are described, eleven being detected on routine scans of women with no relevant history. As most cases of osteogenesis imperfecta type IIA are dominant sporadic mutations, the importance of prenatal diagnosis during routine scanning at a local level is emphasized. In addition to characteristic broad, shortened and fractured long bones, striking features of the chest and head are highlighted which may be encountered during a routine scan, prompting further assessment.     

Prenatal diagnosis of campomelic dysplasia by ultrasonography

Consanguineous partners had a boy with campomelic dysplasia who died of increasing respiratory distress soon after birth. The next pregnancy was monitored frequently by ultrasonography and a healthy male infant was born at term. During a further pregnancy, ultrasonography suggested campomelic dysplasia in the 16th week of gestation. This was confirmed in the 18th week. The pregnancy was terminated and the fetus showed the typical radiological, anatomical and histological findings.