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The standard pedigree used by geneticists is intimately connected to the history of genetics. Pedigrees drawn today are based on standards established in the early decades of the twentieth century. Those standards were established by geneticists who pursued an active interest in eugenics. The slightly different standards followed in America vs. England to some extent followed the stronger support of Mendelism by the Americans, as well as the individual preferences of the leading human geneticists in those countries.

The murine cDNA, encoding the purine catabolic enzyme, ecto-5'-nucleotidase (NT), was cloned and the tissue-specific distribution of both the mRNA and enzyme activity was examined. Starting with kidney RNA and primers based on the known rat sequence, reverse transcriptase-polymerase chain reaction (RT-PCR) was utilized to obtain the complete sequence for the translated portion of the murine cDNA. Murine NT is 94% identical to human NT at the amino acid (aa) level and 86% identical at the nucleotide (nt) level. NT enzyme assays revealed greater than tenfold more NT activity in mature vs. immature murine T- and B-lymphocytes. A similar increase in NT activity was also found when the pre-B-cell line, 70Z/3, was induced to produce surface kappa light chains with lipopolysaccharide (LPS) and gamma-interferon (gamma-IFN). Thus, culture systems in which murine lymphocytes mature may be useful for examining the mechanisms of NT gene regulation, as well as the function of NT in the immune system. In tissues, enzyme activity varied over 30-fold, from the lowest levels in skeletal muscle, thymus and spleen to highest in placenta, kidney and forestomach. Levels of mRNA, as determined by RNase protection assay, showed increased NT expression in the early gestation site, as compared to non-pregnant uterus, and in day-19.5 placenta, as compared to day-13 chorioallantoic placenta. Messenger RNA levels were in general proportional to enzyme activity, except in the lung and glandular stomach where mRNA levels were higher than expected, based on enzyme activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Hyperechogenic bowel was identified among 55 of 6781 (0.81%) fetuses prior to second-trimester genetic amniocentesis. Trisomy 21 was found in eight of the 55 (14.5%) fetuses identified with hyperechogenic bowel compared to 60 of 6726 (0.89%) fetuses with normal bowel echogenicity (p < 0.001). Hyperechogenic bowel carried a 16-fold greater risk for Down's syndrome than normal bowel echogenicity (relative risk 16.8, 95% confidence intervals 8.2-32.5). Chromosome abnormalities other than trisomy 21 were found in four additional fetuses with hyperechogenic bowel (two triploid and one each with 47,XXX; 45,X/47,XXX mosaicisim). Combining these four cases with the eight fetuses having trisomy 21, 21.8% (12 of 55) of fetuses with hyperechogenic bowel proved to have a chromosome abnormality. We conclude that hyperechogenic bowel is associated with chromosome abnormalities, particularly Down's syndrome, when detected during the second trimester., (Copyright 1993 International Society of Ultrasound in Obstetrics and Gynecology)

Clinical outcomes of 95 second-trimester fetuses prospectively considered to have echogenic bowel at ultrasound were compared with a control group of 110 consecutive second-trimester fetuses. Among the 95 fetuses in the study group, 64 (67%) had moderately echogenic (grade 2) or markedly echogenic (grade 3) bowel relative to the liver. Among the 110 fetuses in the control group, only two (1.8%) had moderately echogenic (grade 2) bowel; the rest (98.2%) had isoechoic (grade 0) or midly echogenic (grade 1) bowel relative to the liver. Adverse outcomes occurred in 45 of the 95 fetuses (47%) with echogenic bowel compared with eight of the 110 fetuses (7.27%) in the control group (P < .01; relative risk, 6.5; 95% confidence interval, 3.2, 13.1). Adverse outcomes included chromosomal abnormalities, intrauterine growth retardation, fetal demise, or other fetal anomalies. Within the study group, adverse outcomes occurred in 40 of the 64 fetuses (62%) with grade 2 or 3 bowel echogenicity, compared with five of the 31 fetuses (16%) with grade 1 echogenicity. Echogenic bowel is associated with an increased risk of adverse fetal outcome and this risk is confined primarily to grades 2 and 3 echogenicity.

Objective: Unexplained elevations in maternal serum alpha-fetoprotein in the midtrimester are associated with adverse pregnancy outcome. Recently it has also been suggested that elevations of maternal serum human chorionic gonadotropin in the second trimester may be associated with adverse pregnancy outcome., Study Design: We conducted a cohort study of 460 women at Swedish Medical Center, Seattle, Washington, between Jan. 1, 1990, and Aug. 15, 1991, inclusive. Entry criteria for the cohort included (1) triple screen analysis (maternal serum alpha-fetoprotein, human chorionic gonadotropin, unconjugated estriol) between 15 and 18 weeks' gestation, (2) a risk for Down syndrome of more than one in 195 on the basis of triple screen analysis, (3) study group human chorionic gonadotropin > or = 2 multiples of the median and referent group < or = 2 multiples of the median, alpha-fetoprotein < or = 2 multiples of the median, unconjugated estriol > or = 0.5 multiples of the median, and (4) chromosomally normal single gestation without anomalies. Cumulative incidence risk ratios were estimated for each pregnancy outcome as a measure of the relative association with elevated human chorionic gonadotropin (> or = 2.0 multiples of the median) and adverse pregnancy outcome: low birth weight, < or = 2500 gm; preterm delivery, < 37 weeks' gestation; and small for gestational age, < or = 10th percentile. The Mantel extension test was used to evaluate any apparent linear trend in risk between level of human chorionic gonadotropin and adverse pregnancy outcome., Results: Elevated human chorionic gonadotropin levels were associated with an increased risk for low birth weight (relative risk = 4.0), preterm delivery (relative risk = 2.8), and small for gestational age (relative risk = 1.8). The risk for each adverse outcome increased with increasing levels of human chorionic gonadotropin., Conclusions: Elevations of human chorionic gonadotropin in the midtrimester appear to be associated with adverse pregnancy outcome. The magnitude of the risk correlates with the level of human chorionic gonadotropin. This risk appears to be independent of the risk for adverse pregnancy outcome associated with unexplained elevations of maternal serum alpha-fetoprotein.

Prenatal sonographic findings were reviewed in 47 consecutive fetuses with trisomy 18. One or more abnormalities, excluding choroid plexus cysts, were found in 39 fetuses (83%), including 21 of 29 (72%) fetuses examined between 14 and 24 weeks and all 18 (100%) fetuses examined after 24 weeks. Abnormalities most frequently detected before 24 weeks included cystic hygromas, nuchal thickening, and meningomyelocele. Intrauterine growth retardation, cardiac defects, and an enlarged cisterna magna were detected more frequently after 24 weeks than before 24 weeks (P < 0.05). Intrauterine growth retardation was the single most common abnormality, detected in 51% of all fetuses and 89% of fetuses examined after 24 weeks. Choroid plexus cysts were identified in 25% (12 of 47) of fetuses, including 11 of 29 (38%) fetuses seen before 24 weeks. Additional abnormalities were identified in 10 of 12 (83%) fetuses with choroid plexus cysts; one of the two remaining fetuses showed clenched hands and a cardiac anomaly at autopsy, and the other showed unusually large, multiple choroid plexus cysts. Awareness of the type of anomalies and the usual menstrual age of diagnosis in fetuses with trisomy 18 should improve patient counseling and prenatal detection of fetuses considered at risk for this disorder.

Objective: Our purpose was to determine the utility of screening for humerus and femur length shortening in prenatal detection of Down's syndrome (trisomy 21)., Study Design: On the basis of the biparietal diameter, predicted humerus and femur lengths were derived from a sample control group of 350 karyotypically normal fetuses. The regression formulas were prospectively applied to 45 consecutive fetuses with Down's syndrome and 942 fetuses with normal karyotypes. Ratios of measured humerus length/predicted humerus length and measured femur length/predicted femur length were calculated for each fetus., Results: Eleven of 45 (24.4%) fetuses with Down's syndrome had short humerus (measured humerus length/predicted humerus length ratio of < or = 0.89), and 11 (24.4%) had short femur (measured femur length/predicted femur length ratio of < or = 0.91. In comparison, among 942 karyotypically normal fetuses only 43 (4.5%) showed short humerus and 44 (4.7%) showed short femur (p < 0.05). Fetuses with both short humerus and short femur carried an 11-fold greater risk of Down's syndrome (risk ratio = 11.1; 95% confidence interval = 5.0 to 25.0)., Conclusion: Prenatal ultrasonographic detection of short humerus to short femur, or both significantly increase the risk of Down's syndrome; this information may be useful in screening programs.

To study the possible association between transcervical chorionic villus sampling and midtrimester oligohydramnios, we conducted a prospective cohort study of all women who were seen for genetic counseling in the first trimester during a 2-year period. Women who chose chorionic villus sampling were compared with women who chose traditional amniocentesis for incidence of midtrimester oligohydramnios. Of 442 women exposed to chorionic villus sampling with a normal fetal karyotype, severe oligohydramnios developed in 12 (2.7%) at 16 to 23 weeks' gestation. None of the 391 women with normal fetal karyotypes who were counseled at the same time in pregnancy but who chose amniocentesis had oligohydramnios at the time of amniocentesis (p = 0.01). A nested case-control analysis was performed within the chorionic villus sampling group to evaluate risk factors associated with midtrimester oligohydramnios. Midtrimester oligohydramnios occurring after chorionic villus sampling was associated with postprocedure bleeding and elevated maternal serum alpha-fetoprotein (p less than 0.01). There were no perinatal survivors with midtrimester oligohydramnios.

A case is presented of twin gestation in which one gestational sac was completely resorbed and the remaining twin was subsequently found to be sirenomelic. First-trimester prenatal ultrasound examination demonstrated a second gestational sac that disappeared 2 weeks later. The sonographic features that led to the diagnosis of sirenomelia in the remaining fetus included severe renal dysgenesis, persistently apposed lower extremities, and absence of fibulae. Postmortem examination, including angiographic studies of the fetus, revealed caudal dysgenesis and a single umbilical artery that arose from the abdominal aorta. Sirenomelia occurs more frequently in twin gestations than in singletons. This case suggests that the association between twinning and sirenomelia may be greater than is currently recognized. Two hypotheses are given to explain this association.

Prenatal ultrasound findings were reviewed in 94 consecutive fetuses with proved Down syndrome (trisomy 21) during a 6-year period at a single institution. One or more abnormalities were found in 31 fetuses (33%), including two of 11 fetuses seen before 14 weeks, 17 of 68 fetuses seen between 14-24 weeks, and 12 of 15 fetuses seen after 24 weeks. Major anomalies detected included cardiac defects (five), duodenal atresia (four), cystic hygromas (four), omphalocele (two), hydrops (two), and hydrothorax (one). Nuchal thickening was observed in five fetuses, including four of 25 second-trimester fetuses evaluated prospectively during the last 2 years of the study. Mild cerebral ventricular dilatation (three) and hyperechogenic bowel (five) are new findings that have not been generally associated with Down syndrome. A variety of prenatal sonographic abnormalities may be associated with Down syndrome, and the frequency of detecting most abnormalities increases with menstrual age. Anomalies more frequently detected before 20 weeks include cystic hygromas, nuchal thickening, and hyperechogenic bowel. Awareness of the sonographic findings associated with Down syndrome should result in improved detection of this disorder.

The potential utility of screening for femur length shortening in prenatal detection of Down syndrome (trisomy 21) was evaluated by comparing 49 consecutive fetuses with Down syndrome with 572 chromosomally normal fetuses before genetic amniocentesis. Ratios of measured femur length/predicted femur length and biparietal diameter/femur length were calculated for each fetus. The predicted femur length was calculated from a regression equation relating the biparietal diameter and femur length derived from a sample control group. With this normal regression equation, 7 of 49 (14.3%) fetuses with Down syndrome had short femur lengths (measured femur length/predicted femur length ratio of less than or equal to 0.91) compared with 35 of 572 (6.1%) fetuses with a normal karyotype (p less than 0.05). However, the maximum positive predictive value for identification of Down syndrome based on short femur lengths was only 0.93% for a high-risk population (prevalence of Down syndrome, 1:250) and 0.33% for a low-risk population (prevalence of Down syndrome, 1:700). We conclude that ultrasonographic screening of short femur length is less effective for prenatal detection of Down syndrome than initially suggested.

Maternal serum alpha-fetoprotein (MS-AFP) screening has become part of routine obstetric care. Although elevated MS-AFP was originally associated with neural tube defects (NTD), it is also able to detect several fetal anomalies of interest to a pediatric surgeon, ie, ventral abdominal wall defects, intestinal atresias, and sacrococcygeal teratomas. Previously, decreased MS-AFP had only been associated with fetal trisomies, but not surgically correctable lesions. In the present study, we review our recent experience with both elevated and decreased MS-AFP as a marker to detect fetal anomalies of concern to the pediatric surgeon. Forty-one fetal anomalies were associated with 333 pregnancies referred for follow-up after abnormal MS-AFP screening results from November 1985 through November 1986. One hundred ninety-six were elevated and 139 were decreased. In most cases, evaluation included counseling, repeat MS-AFP, level II ultrasound, and amniocentesis. This revealed elevated MS-AFP to be associated with 32 (16.3%) anomalies (2 NTD, 5 anencephalics, 5 ventral abdominal wall defects, 1 stage IV-S neuroblastoma, 1 renal anomaly, 1 ventriculomegaly, 15 fetal demises, and 2 fetal-maternal bleeds). Decrease in MS-AFP was associated with nine (6.4%) anomalies (2 congenital diaphragmatic hernias, 3 Down's syndrome, 1 Turner's syndrome, 2 duodenal atresias, and 1 choroid plexus cyst). In this study, MS-AFP detected several fetal anomalies known to be associated with abnormal MS-AFP and three anomalies not previously described (congenital diaphragmatic hernia, neuroblastoma, and choroid plexus cyst). Elevated as well as decreased MS-AFP are significant and should be pursued by a full prenatal evaluation.(ABSTRACT TRUNCATED AT 250 WORDS)

We report a case of an umbilical cord hemangioma associated with extremely high alpha-fetoprotein levels in maternal serum and amniotic fluid, as well as a positive acetylcholinesterase band.

We report on 2 cases of fetal congenital diaphragmatic defects with normal chromosomes among 105 patients referred for evaluation for low maternal serum alpha-fetoprotein (MSAFP) levels. The mechanism for this striking association is not clear. The association of low MSAFP levels and congenital diaphragmatic defects may have importance for MSAFP screening programs.