Genetic drift. Just watching.
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Decision Making↗
Biomedical subjects
R G Resta
Publications and source records attributed to R G Resta.
Age-adjusted ultrasound risk assessment for fetal Down's syndrome during the second trimester: description of the method and analysis of 142 cases.
OBJECTIVE: To describe and test a method of individual risk assessment for fetal Down's syndrome based on maternal age and second-trimester ultrasound findings. DESIGN: A case-control study of 142 fetuses with Down's syndrome was compared with 930 control fetuses with normal karyotype. All patients underwent second-trimester ultrasound at a single institution with a standardized ultrasound protocol without knowledge of fetal karyotype. Age-adjusted ultrasound risk assessment (AAURA) for Down's syndrome was performed by multiplying the a priori risk, based on maternal age, with likelihood ratios resulting from the presence or absence of specific ultrasound findings for each patient. Individual ultrasound findings were assigned likelihood ratios (LR) as follows: structural abnormality (LR 25), nuchal thickening (LR 18.6), echogenic bowel (LR 5.5), shortened humerus (LR 2.5), shortened femur (LR 2.2), echogenic intracardiac focus (LR 2), and renal pyelectasis (LR 1.6). A normal ultrasound was assigned a LR of 0.4. RESULTS: One or more ultrasound markers were identified in 68.3% (97) of fetuses with Down's syndrome compared to 12.5% of fetuses with normal karyotype. Among fetuses with positive ultrasound, 31% of those with Down's syndrome and 80% of those with normal karyotype showed a single non-structural finding. Using AAURA and a threshold of 1: 200, 74% (105 of 142) of fetuses with Down's syndrome were identified, including 61.5% (24 of 39) from women aged less than 35 years, 67.2% (45 of 67) from women aged 35-39 years inclusively, and 100% (36 of 36) from women aged 40 years or older. AAURA of 930 fetuses with normal karyotype showed an overall false-positive rate of 14.7%, including 4% (21 of 519) from women aged less than 35 years, 12.5% (42 of 337) from women aged 35-39 years inclusively, and 100% from women aged 40 years or older. CONCLUSIONS: AAURA permits improved individual counselling regarding the risk of fetal Down's syndrome following a second-trimester sonogram. For low-risk women under age 35 years, ultrasound assessment can identify over half of the affected fetuses with Down's syndrome with an acceptable false-positive rate (4%). For women aged 35-39 years, a normal ultrasound can substantially reduce the risk of unnecessary amniocentesis (12.5% from 100%) but will also miss approximately one-third of affected fetuses. Biochemical screening of maternal serum is also suggested for this group. Based on their high a priori risk, women aged 40 years or more should consider genetic amniocentesis regardless of a normal ultrasound.
Adolescent↗
Urinary gonadotropin peptide levels in preeclamptic and normotensive pregnant women. Results from a pilot case-control study.
OBJECTIVE: Elevated maternal serum human chorionic gonadotropin (hCG) is an important marker of Down syndrome. Notably, women with unexplained elevated serum hCG in the second trimester experience a 2- to 5-fold increase risk of preeclampsia. Urinary gonadotropin peptide (UGP), thought to be a metabolite of hCG that is excreted into urine, has recently been shown to be elevated in Down syndrome pregnancies. We sought to examine urinary UGP levels in preeclamptic and normotensive pregnant women. METHODS: We measured UGP levels in urine collected during the third trimester from 18 women with preeclampsia and 20 normotensive controls. UGP levels were determined using enzyme immunoassay and were corrected for dilution using urinary creatinine. Statistical significance testing was done using the Wilcoxon-Mann-Whitney Rank Sum test and Student t test statistics. RESULTS: There was a statistically significant elevation in urinary UGP levels among preeclamptic cases as compared to normotensive control subjects (p = 0.013). Mean urinary UGP levels were 80.7 and 31.3 pmol/mg creatinine for preeclampsia cases and controls, respectively. Elevations in UGP levels among women with preeclampsia as compared with normotensive control subjects persisted after adjustments for possible confounding factors. CONCLUSION: These early findings suggest that elevations in urinary UGP may be a risk marker for preeclampsia. Prospective studies should further clarify the relation between urinary UGP levels and adverse pregnancy outcomes. These results are consistent with results suggesting a role of placental hypoperfusion in the etiology of preeclampsia.
Adult↗
Carolyn's feet.
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Abnormalities, Multiple↗
Follow-up of a familial translocation t(10;16) with an unusual segregation pattern.
Bofinger et al. [Am J Med Genet 38:1-8, 1991] reported on a four-generation family with an unusual segregation pattern involving a translocation t(10;16)(q26.3;p13.1). All relatives either had a balanced or unbalanced translocation. We report on five additional relatives, none of whom have a normal karyotype. This unusual segregation pattern may be due to chance or be the result of meiotic drive.
Abnormalities, Multiple↗
Prenatal diagnosis of uniparental disomy 15 following trisomy 15 mosaicism.
Maternal uniparental disomy 15 (UPD15), responsible for approximately 25 per cent of Prader-Willi syndrome cases, is usually caused by maternal meiosis I non-disjunction associated with advanced maternal age. These cases may initially be detected as mosaic trisomy 15 during routine prenatal diagnostic studies. In such cases, PCR (polymerase chain reaction) microsatellite analysis of uncultured cells makes prospective prenatal diagnosis for UPD15 possible with results available in 2-4 days. We have performed molecular analyses on a series of seven cases of mosaic trisomy 15 identified in amniotic fluid (AF, n = 3) or chorionic villus samples (CVS, n = 4) from patients initially referred for advanced maternal age or abnormal triple screen. In all cases, the maternal ages were > or = 35 years and maternal meiosis I non-disjunction was documented as the cause of the trisomy in all informative cases (n = 5). Of the three case with mosaic trisomy 15 at amniocentesis, two showed the presence of the trisomy in the fetus. Molecular analysis showed one case with maternal UPD15 in the euploid cell line and one case with biparental inheritance. Both of these families elected to terminate the pregnancies based on the presence of true fetal mosaicism. In the third case, low-level trisomy 15 mosaicism in the amniotic fluid was not confirmed in a follow-up amniotic fluid sample and molecular analysis indicated biparental inheritance in the fetus. For the four trisomy 15 mosaics detected at CVS, molecular analysis was performed on direct amniotic fluid cell lysates for prospective diagnosis of UPD at 14-16 weeks' gestation. Follow-up cytogenetic analysis of the amniotic fluid in all four cases was normal, indicating confined placental mosaicism. Molecular analysis showed one of these four cases to have maternal heterodisomy 15. Based on the likelihood of Prader-Willi syndrome due to maternal UPD15, the couple chose to terminate the pregnancy. The total of two of seven cases of trisomy 15 mosaicism resulting in UPD15 is consistent with the theoretical expectation of one-third and indicates a high risk of UPD in such pregnancies. Therefore, UPD testing should be offered in all cases of mosaic trisomy 15 encountered in CVS or amniocentesis.
Adult↗
Inconsistencies in pedigree symbols in human genetics publications: a need for standardization.
To determine consistency in usage of pedigree symbols by genetics professionals, we reviewed pedigrees printed in 10 human genetic and medical journals and 24 medical genetics textbooks. We found no consistent symbolization for common situations such as pregnancy, spontaneous abortion, death, or test results. Inconsistency in pedigree design can create difficulties in the interpretation of family studies and detract from the pedigree's basic strength of simple and accurate communication of medical information. We recommend the development of standard pedigree symbols, and their incorporation into genetic publications, professional genetics training programs, pedigree software programs, and genetic board examinations.
Genetics, Medical↗
Role of prenatal ultrasonography in women with positive screen for Down syndrome on the basis of maternal serum markers.
OBJECTIVE: Our purpose was to evaluate the usefulness of prenatal ultrasonography among women with a positive screen for fetal Down syndrome on the basis of three biochemical markers--maternal serum alpha-fetoprotein, human chorionic gonadotropin, and unconjugated estriol. STUDY DESIGN: A total of 395 women underwent prenatal ultrasonography at a single institution after being identified as screen positive (midtrimester risk > or = 1:195) on the basis of triple-marker screening between 15 and 18 weeks. Ultrasonographic findings were compared with the biochemical markers and the eventual fetal outcome for these patients. Ultrasonographic abnormalities that were evaluated included structural defects, nuchal thickening or cystic hygroma, echogenic bowel, cerebral ventricular dilatation, pyelectasis, and shortened femur. RESULTS: Among 395 patients, 374 (94.7%) had normal karyotype by genetic amniocentesis (n = 232) or postnatal follow-up (n = 142), 18 (4.5%) proved to have Down syndrome, and three had other karyotypic abnormalities. One or more ultrasonographic abnormalities were found in nine of 18 (50%) with Down syndrome compared to 27 of 377 (7.2%) other fetuses (p < 0.001). Fetuses with abnormal ultrasonography results included three with other chromosome abnormalities and five with nonchromosomal anomalies. An abnormal ultrasonography result increased the risk of Down syndrome by 5.6-fold (25% from 4.5%) and a negative result reduced the risk by 45% (2.5% from 4.5%). The value of ultrasonography is further enhanced when all chromosome abnormalities and nonchromosomal anomalies are considered. CONCLUSION: Abnormal ultrasonographic findings increase the risk for Down syndrome, whereas normal findings are less predictive of normalcy. After correction for inaccurate menstrual dates, genetic amniocentesis should be offered in spite of a normal ultrasonography result among women with positive triple screen.
Adult↗
Trisomy 13 syndrome: prenatal US findings in a review of 33 cases.
PURPOSE: To determine the type and prevalence of prenatal ultrasound (US) findings in fetuses with trisomy 13. MATERIALS AND METHODS: Prenatal US findings in 33 consecutive fetuses with trisomy 13 and in 200 karyotypically normal fetuses were reviewed and compared. RESULTS: One or more abnormalities were found in 30 fetuses (91%). Major anomalies detected by means of US included holoprosencephaly (13 [39%]) or other central nervous system anomalies (19 [58%]), facial anomalies (15 [48%]), and renal (11 [33%]) and cardiac (16 [48%]) defects. Growth retardation was also present in 16 (48%). Echogenic chordae tendineae were seen in 10 (30%), which includes seven (39%) of 18 fetuses examined before 20 menstrual weeks (compared with four [2%] of 200 fetuses in the reference group [P < .001]). Other findings not generally associated with trisomy 13 but present in this series included a large cisterna magna (six [18%]), mild cerebral ventricular dilatation (three [9%]), nuchal thickening or cystic hygroma (seven [21%]), and a hypoplastic left side of the heart (seven [21%]). CONCLUSION: Prenatal US can help detect one or more anomalies in most fetuses with trisomy 13; thus, US finding can indicate whether karyotype should be tested.
Adolescent↗
Recommendations for standardized human pedigree nomenclature. Pedigree Standardization Task Force of the National Society of Genetic Counselors.
The construction of an accurate family pedigree is a fundamental component of a clinical genetic evaluation and of human genetic research. Previous surveys of genetic counselors and human genetic publications have demonstrated significant inconsistencies in the usage of common pedigree symbols representing situations such as pregnancy, termination of pregnancy, miscarriage, and adoption, as well as less common scenarios such as pregnancies conceived through assisted reproductive technologies. The Pedigree Standardization Task Force (PSTF) was organized through the Professional Issues Committee of the National Society of Genetic Counselors, to establish recommendations for universal standards in human pedigree nomenclature. Nomenclature was chosen based on current usage, consistency among symbols, computer compatibility, and the adaptability of symbols to reflect the rapid technical advances in human genetics. Preliminary recommendations were presented for review at three national meetings of human genetic professionals and sent to > 100 human genetic professionals for review. On the basis of this review process, the recommendations of the PSTF for standardized human pedigree nomenclature are presented here. By incorporating these recommendations into medical genetics professional training programs, board examinations, genetic publications, and pedigree software, the adoption of uniform pedigree nomenclature can begin. Usage of standardized pedigree nomenclature will reduce the chances for incorrect interpretation of patient and family medical and genetic information. It may also improve the quality of patient care provided by genetic professionals and facilitate communication between researchers involved with genetic family studies.
Genetic Counseling↗
Humerus and femur length shortening in the detection of Down's syndrome.
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.
Bone Lengthening↗
Echogenic fetal bowel during the second trimester: clinical importance.
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.
Chromosome Aberrations↗
Prenatal sonographic findings of trisomy 18: review of 47 cases.
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.
Abnormalities, Multiple↗
Sirenomelia associated with a "vanishing twin".
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.
Adult↗
Transcervical chorionic villus sampling and midtrimester oligohydramnios.
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.
Adult↗
Femur length shortening in the detection of Down syndrome: is prenatal screening feasible?
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.
Cephalometry↗
Prenatal sonographic findings of Down syndrome: review of 94 cases.
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.
Abnormalities, Multiple↗