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Similar concerns have been noted previously for a different disease and distinct enzyme deficiency. In 1973 Vidgoff and associates 1~ reported a family which included a woman with a marked deficiency of hexosominidase A in all tissues studied. She actually represents the carrier state for Tay-Sachs disease, though her hexosominidase A level taken alone would have suggested that she was an affected homozygote. There are thus at least two heritable disorders for which there is overlap between the carrier and the affected person in terms of enzyme activity. Based on these findings, and considering the greater availability and less strict indications for prenatal diagnostic amniocentesis, it is suggested that great care be exercised in the diagnosis of these diseases, particularly in the interpretation of data for intrauterine diagnosis. The data and conclusions discussed here were presented in preliminary form to the Society for Pediatric Research, Denver, April 18, 1975.11

UNTIL very recently fetal cardiology was restricted to the study of the embryology of the fetal heart with the primary emphasis on the understanding of the development of structural congenital cardiac abnormalities. Cardiology, and in this sense pediatric cardiology, started with the birth process and was again primarily directed toward recognition, diagnosis, and therapy of neonatally recognized structural congenital heart problems. During the last decade, the fetal heart has attracted increasing interest both on the part of the obstetrician-perinatologist and the pediatric cardiologist. Research into the developing heart has concentrated on embryology but has covered such important areas as the biophysics of the developing heart, the autonomic control of fetal cardiac activity, as well as genetic, infectious, metabolic, and environmental causes for congenital heart abnormalities. The advances and the understanding of basic physiology of the fetal heart as well as the development of newer diagnostic means have, in turn, improved

This is a report of 327 phone calls to our center concerning the intrauterine diagnosis of sex chromosome abnormalities (SCA). The first author (A.R.) responded to each by counseling either the parents or the referring professional. Sixty-two percent continued the pregnancy. When the parents were counseled directly, the percentage continuing the pregnancy was significantly higher than when the information was transmitted through the professionals. Our results are different from most reports in these situations, and suggest that well-informed couples, counseled by geneticists, are more likely to continue these pregnancies. The possible occurrence of SCA should be considered in preamniocentesis counseling.

The results are reported of the intrauterine diagnosis of fetal thalassaemia in 72 pregnant women investigated during the six years from 1977 to 1982. In the majority of cases fetal blood was collected by fetoscopy for globin chain synthesis at 18 to 19 weeks' gestation. Adequate fetal blood samples for the diagnosis of the thalassaemia status of the fetus were obtained in 85% of cases. The technical difficulties associated with fetoscopy and fetal blood collection are discussed, and the maternal and fetal complications of the procedure described.

• The diagnosis of renal disease was made antenatally in three patients by ultrasonographic examination. In two cases a multicystic kidney was detected in utero and removed shortly after delivery. In another case, a hydronephrotic kidney was detected in utero; repair was then performed early, before symptoms developed in the infant. Antenatal diagnosis of renal disease by ultrasonography may help reduce morbidity and mortality in some cases. ( Am J Dis Child 133:1042-1043, 1979)

This case report describes the antenatal diagnosis of a fetal pulmonary anomaly. Early detection afforded detailed parental counseling and prompt neonatal diagnosis and treatment.

Rapid expansion of our knowledge of the biochemical basis of inherited metabolic disorders during recent years and the development of new diagnostic methods have led to rapid advances in the intrauterine diagnosis of the inborn errors of metabolism. Amniocentesis continues to be the primary tool. Cell-free amniotic fluid, noncultivated amniotic fluid cells, and cultivated amniotic fluid cells have all been utilized in the prenatal diagnosis of inborn errors of metabolism, and, given the appropriate circumstances, each may provide important information regarding the status of the fetus. The accuracy of prenatal biochemical diagnosis has generally been very high, but errors have occurred. It is of paramount importance that extreme caution be exercised in the interpretation of prenatal studies. In many instances, a decision as to whether or not a pregnancy will be continued is based on the result of a single laboratory study. The responsibility entrusted to those involved in prenatal diagnostic studies is therefore great. It is essential that everyone involved in such endeavors be thoroughly familiar with the origin and characteristics of normal amniotic fluid and amniotic fluid cells. The normal variability in any biochemical or cytological characteristic must be well defined before the results obtained from a particular analysis can be assumed to represent fetal abnormality.

Five patients have been classified as suffering from mucolipidosis type IV on the basis of the findings in various tissues and in cultured fibroblasts. The light and electron microscopic features of cultured fibroblasts in this disease are described in detail. The differentiation of this condition from other lysosomal storage diseases and other types of mucolipidoses is discussed. The importance of identifying this disease for purposes of intrauterine diagnosis and eventual understanding of the underlying enzyme defect is stressed.

A case of fetal epignathus was evaluated by 2 new approaches (morphological and functional) using ultrasonic tomography. In the morphological study, serial interval tomograms were converted using a microcomputer into 3-dimensional images for easier and more accurate diagnosis. In respect to function of cardiovascular system, not only placental enlargement and overswelling of the internal jugular vein were observed, but elevated function in the fetal left ventricle and hypofunction in the right ventricle were revealed by M-mode ultrasonography. The evidence from these examination and the autopsy seemed to support the double monster theory for the origin of epignathus.

At a time when the intrauterine diagnosis of hydrocephalus is common and pioneering efforts of antenatal therapy are evolving, an assessment of intrauterine treatment of this disorder becomes pertinent. Consequently, the current status of the intrauterine treatment of fetal hydrocephalus is presented. The new data from the International Fetal Surgery Registry at the University of Manitoba in Winnipeg are discussed. The technical problems of antenatal shunting, the clinical trials, and experimental treatment are assessed. The prognostication and possible new approaches in intrauterine treatment of hydrocephalus are presented as well as the new diagnostic and surgical techniques. The outcome of the antenatal diagnosis and treatment of fetal hydrocephalus is evaluated.

The authors present a case of congenital dislocation of the knee diagnosed in utero, when an abdominal radiograph was performed on a woman in the eighth month of pregnancy.

Modern ultrasound equipments allow a detailed investigation of the fetal brain from a very early stage of development. Congenital anomalies arising from or involving the central nervous system can be accurately predicted. On the basis of their personal experience, which includes 48 cases, and of a review of the current literature, the authors discuss criteria for the intrauterine diagnosis and obstetrical management of intracranial anomalies such as hydrocephalus, holoprosencephaly, cephaloceles, porencephaly, hydranencephaly, and microcephaly.

Amniocentesis, the obtaining of a small amount of amniotic fluid with fetal cells for testing, has made it possible to diagnose some diseases in utero early enough in pregnancy to permit abortion. The current major indications for prenatal diagnosis are Down's syndrome (Trisomy 21), numerous rare inborn errors of metabolism, and neural tube closure defects. Chromosoml screening in prisons has identified men with sex chromosomal abnormalities with higher frequency than in the general population, e.g., the XYY syndrome and the XXY or Klinefelter syndrome. Some of the disorders of sexual differentiation of behavioral interest range from hermaphrodites, the Turner syndrome, congenital adrenal hyperplasia, and testicular feminization. Depression and schizophrenia are 2 psychiatric disorders that are probably influenced by genetic factors but cannot be tested for at present. Behavioral syndromes associated with abnormal chromosomes or biochemical markers may be suitable for early detection int he future. There are many social and psychological problems in testing and counseling for genetic and chromosomal diseases.

Intrauterine Diagnosis: Comparative Enzymology of Cells Cultivated from Maternal Skin, Fetal Skin, and Amniotic Fluid Cells

The establishment of drug testing protocols for teratogenic screening resulted primarily from the thalidomide episode. Although many laboratories throughout the world had developed their own personalized methodology for studying potential teratogenic agents, the quality of these investigations ranged from very good to very bad. In the 1960’s, numerous publications of committees and individuals reported or suggested various protocols for teratogenic screening of drugs. One must remember that a protocol for teratogenic screening is empirically derived, primarily because many of the basic mechanisms of teratogenesis in mammals is unknown. Developing protocols for teratogenic screening is applied research and of the most empirical type.

CHROMOSOME karyotypes and enzyme analyses of cultured amniotic-fluid cells obtained during the second trimester have permitted reliable identification of affected and unaffected fetuses in pregnancies at high risk for certain specific birth defects or genetic disorders.1 2 3 4 However, a testable abnormality is known for relatively few conditions.2 3 4 5 We report here radiographic visualization of the fetus in a pregnancy at 25 per cent risk for the syndrome of thrombocytopenia and absent radii. Case Report A 26-year-old woman was referred to the Genetics Counseling Clinic in the 8th week of pregnancy. A previous pregnancy had resulted in a son affected with phocomelia and . . .

Five disorders of collagen have been characterized. In four of these disorders the patients have had symptoms of Ehlers Danlos. Three families with lysyl hydroxylase deficiency have previously been reported. We are reporting an additional case diagnosed in infancy. This infant was investigated as a floppy baby but nerve and muscle were normal. Lysyl hydroxylase activity measured in sonicates of dermal fibroblasts was 10% of normal. The deficiency of hydroxylysine results in abnormal cross-linking of collagen molecules which may account for the symptomatology. The patient we are reporting eventually developed symptoms of Ehlers Danlos. This type of Ehlers Danlos is an autosomal recessive disorder in which one might expect to make an intrauterine diagnosis. Collagen abnormalities may thus be a cause of floppy baby syndrome and the delineation of a specific defect should be the goal of diagnostic studies.

The article by Frigoletto et al, appearing elsewhere in this issue (p 2496), is perhaps the vanguard of pioneering efforts at invasive care of the fetus. The precedent was set almost 20 years ago by Liley, 1 who described successful intrauterine transfusion for severe erythroblastosis. Intrauterine transfusion never became commonplace because Rho(D) immune globulin greatly reduced the number of severely sensitized Rh-negative mothers. However, it has achieved an accepted place in the therapeutic armamentarium. Frigoletto et al report intrauterine diagnosis of hydrocephalus, with percutaneous placement of a ventriculoamniotic shunt under ultrasound guidance. The shunt decompressed the ventricles and allowed pregnancy to continue to a point where a viable newborn was delivered. That the baby later died of probably unrelated causes does not obscure the fact that the feasibility of intrauterine decompression of progressive hydrocephalus was established. While the article further demonstrates the accessibility of the fetus to transabdominal manipulation, it

The Prenatal Diagnosis of Hereditary Disorders by Dr. Aubrey Milunsky was expressly written for physicians, counselors, and other medical personnel who are in a position to counsel families at risk for a variety of genetic disorders. The content of the book is more general than that suggested by the title. The author has had extensive experience with intrauterine diagnosis since the late 1960s and reviews his experience, as well as that of others, relating to prenatal diagnosis. In addition, sections on genetic counseling, genetics and society, and morality, ethics, law, and the future are included. The text is, in general, easy to read, highly accurate, and provides an excellent review of the field up to the time that it was written. The data on amniocentesis are accurate and the experience is reviewed in great detail. The entire text is easily understandable and certainly answers the overwhelming majority of questions

Intrauterine diagnosis places upon the physician the responsibility for making a diagnosis and a prognosis for an individual he has not seen or examined. Prognostication for a fetus with sex chromosomal aneuploidy (SCA) is particularly difficult and varies tremendously in various centers and in various parts of the world. As a result, the message patients get from their counselors and what action patients take varies greatly in different parts of the country. The author has received 86 telephone consults either from counselors or patients from various parts of the U.S.A. and Canada and has followed up the actions taken by these consultands. Two-thirds of couples, who represent a biased selection, have continued the pregnancy, irrespective of the fetal karyotype. The nature of the prognosis and future management of these high risk fetuses, especially the impact of environmental factors and long-term support, will be discussed.

In the ten chapters selected topics of developmental biochemistry are presented by 14 well chosen authors. Sereni and Principi tackled the complicated question of how perinatal liver function is regulated; the authors collected valuable information on this relatively new and little explored topic. A very impressive achievement in intrauterine diagnosis and antenatal detection of inherited diseases is presented by Nyhan who excellently surveys the great number of biochemical disorders with didactic skill. The complicated and complex regulation of genetic expression is described by Benson. This author who also edited the book discusses the ten principal factors involved in protein synthesis, the programmed differential expression of the genome, and the biosynthesis and control of RNA and protein. Walker surveys the development of enzymes for carbohydrate metabolism; he stresses the importance of control mechanisms and rate-controlling enzymes in the perinatal period. The developmental aspects of lipid metabolism are described by Myatt; the