Prospective prenatal diagnosis of Prader-Willi syndrome due to maternal disomy for chromosome 15 following trisomic zygote rescue.

We present a prenatal predictive diagnosis of Prader-Willi syndrome arising as a result of maternal heterodisomy for chromosome 15. The diagnosis arose following chorionic villus sampling which showed a mosaic trisomy 15 karyotype with a chromosomally normal follow-up amninocentesis. Molecular studies on DNA extracted from cultured amniocytes showed no evidence of a paternal allele at two widely separated loci and this was taken as evidence of maternal disomy predictive of Prader-Willi syndrome in the fetus.

Congenital diaphragmatic hernia with probable autosomal recessive inheritance in an extended consanguineous Pakistani pedigree.

We report four cases of congenital diaphragmatic hernia occurring in two generations of a consanguineous Pakistani family. The affected subjects resembled no recognised genetic syndrome. This family provides further evidence for possible autosomal recessive inheritance of congenital diaphragmatic hernia in some cases.

Lethal neonatal chondrodysplasias in the West of Scotland 1970-1983 with a description of a thanatophoric, dysplasialike, autosomal recessive disorder, Glasgow variant.

Complete ascertainment of lethal neonatal short-limb chondrodysplasias was attempted in the West of Scotland for the period 1970-1983. Forty-three cases were identified, representing a minimum incidence of 1 in 8,900. The differential diagnosis included 11 well-delineated skeletal dysplasias, one case of warfarin embryopathy, and one apparently new condition with presumed autosomal recessive inheritance that has radiographic similarities to those of thanatophoric dysplasia (TD). In this series TD had an incidence of 1 in 42,221, which is consistent with new dominant mutation at a rate of 11.8 +/- 4.1 X 10(-6) mutations per gene per generation. Ultrasonic measurement of fetal long bone length was performed in eight subsequent pregnancies at risk. Five unaffected fetuses were predicted correctly and three affected fetuses were detected during the second trimester (one with rhizomelic chondrodysplasia punctata-second trimester prenatal diagnosis not previously reported; one with achondrogenesis type II; and one with the new lethal condition).

Maternal serum alpha-fetoprotein in twin pregnancies uncomplicated by neural tube defect.

The maternal serum alpha-fetoprotein concentration was measured between 16 and 20 weeks in 145 twin pregnancies in which neither fetus had a neural tube defect. When the maternal serum alpha-fetoprotein concentration was less than two multiples of the singleton median, pregnancy outcome was good; the extended perinatal mortality rate was 32.6/1000, mean birth weights for the first and second twins were 2507 and 2443 gm, respectively, and mean gestation at delivery was 36 weeks, 6 days. When the maternal serum alpha-fetoprotein concentration was greater than four multiples of the singleton median, the outcome was poor; the extended perinatal mortality was 400/1000, mean birth weights were 1963 and 1523 gm, and mean gestation at delivery was 32 weeks, 4 days. The negative correlations of maternal serum alpha-fetoprotein concentration with birth weight and gestation at delivery were highly significant. Maternal serum alpha-fetoprotein concentration in midpregnancy is a useful predictor of outcome in twin pregnancy, independent of the occurrence of neural tube defect, and it appears to be related to the timing of delivery rather than fetal growth.

Gastroschisis and exomphalos: precise diagnosis by midpregnancy ultrasound.

As part of a regional screening programme for neural-tube defects the cause of the raised alpha-fetoprotein levels was correctly identified in 13 pregnancies with a fetal abdominal wall defect by the 22nd week. Careful ultrasound study identified gastroschisis in seven fetuses and exomphalos in six: the presence or absence of a sac, the course of the umbilical vessels and the abdominal organs involved were the most important diagnostic criteria. Pregnancy continued into the third trimester in five cases complicated solely by gastroschisis and two babies have survived the neonatal period following surgical correction. It is suggested that precise identification by ultrasound of the type and severity of abdominal wall defect and also of the presence or absence of associated anomalies will enable the selection of some babies with gastroschisis or isolated exomphalos which have a good prognosis for survival without handicap.

Aneuploidy and cystic hygroma detectable by ultrasound.

During one year, five second trimester fetuses with cystic hygromata and varying degrees of oedema presented to the authors from hospitals in the West of Scotland. Two fetuses had 45X karyotypes, one each had 47XY + 21 and 47XX + 18 karyotypes, and the fifth had a normal 46XY karyotype. Fetal oedema detectable by ultrasound, affecting particularly the back of the neck, may be a commoner manifestation of several aneuploid syndromes than has hitherto been recognized.

Fetal weight estimation by real-time ultrasound measurement of biparietal and transverse trunk diameter.

Measurements of biparietal diameter and transverse trunk diameter with the use of linear array real-time B-mode scanning were performed on 100 fetuses within 72 hours of delivery to evaluate the reliability of Hansmann and associates, nomogram in predicting fetal weight. Under optimal conditions, 82% of predicted birth weights were within 10% of actual birth weight with a mean error of 150 gm (6%) and a correlation coefficient of 0.98. Predictions were most accurate in fetuses weighing less than 1,500 gm and in the 2,000 to 4,000 gm group and were least accurate in the infant weighing less than 1,500 gm and in the 2,000 to 4,000 gm group and were least accurate in the infant weighing more than 4,000 gm. Once the accuracy of the method was determined, It was applied to 100 consecutive cases to evaluate the feasibility of this technique in clinical practice. Measurements were unobtainable in 15%, but in the remainder, predictions were of sufficient accuracy throughout the range of fetal weights to complement clinical assessment in the management of high-risk pregnancies. Seventy-four percent of predicted weights were within 10% of actual birth weight; the mean error was 165 gm (7.2%) and the correlation coefficient was 0.97.

Uterine growth in twin pregnancy by measurement of total intrauterine volume.

Total intrauterine volume (TIUV) was determined serially in 27 twin pregnancies from which a nomogram was constructed. At the beginning of the second trimester, TIUV was similar to that in singleton pregnancy; by the 18th week it had become twice as large, and remained so until late in pregnancy. Labor was preceded more frequently by a slowing than by an acceleration of uterine growth.

Diagnosis by real time ultrasound of hourglass herniation of the fetal membranes. Two case reports.

We present two patients in whom hourglass herniation of the fetal membranes through the cervix occurred at 26 weeks gestation. The diagnosis was made by real time ultrasound and led to conservative management. One of the infants survived and might well not have done so without conservative management.