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S F Goodburn - One of the best experts on this subject based on the ideXlab platform.
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potter s Syndrome in the second trimester prenatal screening and pathological findings in 60 cases of oligohydramnios sequence
Prenatal Diagnosis, 1995Co-Authors: R J Scott, S F GoodburnAbstract:: Fifty-two second-trimester and eight third-trimester (> 28/40) autopsies with clinical or pathological evidence of oligohydramnios sequence ('Potter's Syndrome') were reviewed. Twenty-eight cases had renal anomalies (71 per cent in terminations following prenatal ultrasound), 27 had no renal Malformation (35 per cent with chorioamnionitis), and five had external assessments only. In 15 cases, the renal lesion was part of a Multiple Malformation Syndrome. Seven cases had a lesion which either recurred in a sibling in the same family or was a recognized autosomal recessive Syndrome. Three cases had an abnormal karyotype, two of which had renal anomalies. Maternal serum alpha-fetoprotein (AFP) did not discriminate between cases with renal Malformations and those without. Pulmonary hypoplasia was commoner in third-trimester than in second-trimester cases. External appearance and absent umbilical artery were not reliable predictors of underlying internal anomalies. These findings reflect the shift from postnatal to prenatal diagnosis in modern practice. In this series, mainly second-trimester cases, 50 per cent of cases had no Malformations, in a condition which is traditionally associated with renal disease. The high incidence of chorioamnionitis suggests that the mechanism of oligohydramnios is occult amniotic fluid leakage. Prenatal diagnosis of oligohydramnios in the second trimester is dependent on ultrasound scanning and a full post-mortem examination is necessary to identify any underlying fetal cause.
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potter s Syndrome in the second trimester prenatal screening and pathological findings in 60 cases of oligohydramnios sequence
Prenatal Diagnosis, 1995Co-Authors: R J Scott, S F GoodburnAbstract:Fifty-two second-trimester and eight third-trimester (> 28/40) autopsies with clinical or pathological evidence of oligohydramnios sequence ('Potter's Syndrome') were reviewed. Twenty-eight cases had renal anomalies (71 per cent in terminations following prenatal ultrasound), 27 had no renal Malformation (35 per cent with chorioamnionitis), and five had external assessments only. In 15 cases, the renal lesion was part of a Multiple Malformation Syndrome. Seven cases had a lesion which either recurred in a sibling in the same family or was a recognized autosomal recessive Syndrome. Three cases had an abnormal karyotype, two of which had renal anomalies. Maternal serum alpha-fetoprotein (AFP) did not discriminate between cases with renal Malformations and those without. Pulmonary hypoplasia was commoner in third-trimester than in second-trimester cases. External appearance and absent umbilical artery were not reliable predictors of underlying internal anomalies. These findings reflect the shift from postnatal to prenatal diagnosis in modern practice. In this series, mainly second-trimester cases, 50 per cent of cases had no Malformations, in a condition which is traditionally associated with renal disease. The high incidence of chorioamnionitis suggests that the mechanism of oligohydramnios is occult amniotic fluid leakage. Prenatal diagnosis of oligohydramnios in the second trimester is dependent on ultrasound scanning and a full post-mortem examination is necessary to identify any underlying fetal cause.
Forbes D Porter - One of the best experts on this subject based on the ideXlab platform.
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altered cerebrospinal fluid proteins in smith lemli opitz Syndrome patients
American Journal of Medical Genetics Part A, 2016Co-Authors: Stephanie M Cologna, Christopher A. Wassif, Simona Bianconi, Christine Shieh, Cynthia L Toth, Antony Cougnoux, Kathryn R Burkert, Forbes D PorterAbstract:Smith-Lemli-Opitz Syndrome (SLOS) is an autosomal recessive, Multiple Malformation Syndrome with neurocognitive impairment. SLOS arises from mutations in the 7-dehydrocholesterol reductase gene which results in impaired enzymatic conversion of 7-dehydrocholesterol to cholesterol. In the current work, we sought to measure proteins that were altered in the cerebrospinal fluid from SLOS patients compared to pediatric controls. Using a multi-analyte antibody-based assay, we found that 12 proteins are altered in SLOS patients. Validation studies were carried out and the findings from this study suggest alterations in extracellular matrix remodeling and further evidence of oxidative stress within the disease pathophysiology. The results of this study will be used to explore biological pathways altered in SLOS and identifies a set of CSF proteins that can be evaluated as biomarkers in future therapeutic trials. © 2016 Wiley Periodicals, Inc.
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adrenal function in smith lemli opitz Syndrome
American Journal of Medical Genetics Part A, 2011Co-Authors: Simona Bianconi, Forbes D Porter, Sandra K Conley, Meg Keil, Ninet Sinaii, Kristina I Rother, Constantine A StratakisAbstract:Smith-Lemli-Opitz Syndrome (SLOS) is a Multiple Malformation Syndrome due to mutations of the 7-dehydrocholesterol reductase gene (DHCR7), which leads to a deficiency of cholesterol synthesis and an accumulation of 7-dehydrocholesterol. The SLOS clinical spectrum ranges from Multiple major Malformations to a mild phenotype with minor anomalies and intellectual disability. Several children with SLOS and adrenal insufficiency have been described. We performed ovine corticotropin (oCRH) testing in 35 SLOS patients and 16 age- and gender-matched controls. We reviewed prior adrenocorticotropin (ACTH) stimulation tests of our SLOS patients (19 of 35 available) and reviewed results of ACTH stimulation tests from 10 additional SLOS patients. Results from oCRH testing showed that patients with SLOS had significantly higher ACTH baseline values than healthy controls (24.8 ± 15.3 pg/ml vs. 17.8 ± 7.5 pg/ml, P = 0.034). However, no statistically significant differences were noted for peak ACTH values (74.4 ± 35.0 pg/ml vs. 64.0 ± 24.9 pg/ml, P = 0.303) and for baseline (14.2 ± 7.8 mcg/dl vs. 14.2 ± 6.3 mcg/dl, P = 0.992) and peak cortisol values (28.2 ± 7.9 mcg/dl vs. 24.8 ± 8.1 mcg/dl, P = 0.156). The area-under-the-curve (AUC) was not significantly different in SLOS patients compared to controls for both ACTH (250.1 ± 118.7 pg/ml vs. 195.3 ± 96.6 pg/ml, P = 0.121) as well as cortisol secretion (83.1 ± 26.1 mcg/dl vs. 77.8 ± 25.9 mcg/dl, P = 0.499). ACTH stimulation test results were normal in 28 of 29 tests. The individual with the abnormal test results had subsequent normal oCRH tests. The slightly increased baseline ACTH level seen during oCRH testing may be due to compensated adrenocortical insufficiency. However, we were able to show that our patients with SLOS had an adequate glucocorticoid response, and thus, in mild to moderate cases of SLOS stress steroid coverage may not be warranted.
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discordant phenotype and sterol biochemistry in smith lemli opitz Syndrome
American Journal of Medical Genetics Part A, 2010Co-Authors: Grace Koo, Sandra K Conley, Christopher A. Wassif, Forbes D PorterAbstract:Smith-Lemli-Opitz Syndrome (SLOS) is a Multiple Malformation Syndrome resulting from mutations of the 7-dehydrocholesterol reductase gene (DHCR7). During de novo cholesterol biosynthesis, DHCR7 catalyzes the conversion of 7-dehydrocholesterol (7DHC) to cholesterol. A clinical diagnosis of SLOS is confirmed biochemically by the presence of elevated levels of 7-dehydrocholesterol. Phenotypic severity of SLOS has previously been shown to correlate with the 7DHC/cholesterol ratio. In this case report, we describe a patient with a severe SLOS phenotype, but a very low serum 7DHC/cholesterol ratio. We further demonstrate that this discordance is due to alternative splicing of a previously unreported IVS5+3 A>T mutation. This mutation results in the transcription of both normal and mutant mRNA transcripts. We postulate that alternative splicing of the IVS5+3 A>T results in insufficient DHCR7 activity during embryogenesis, but sufficient DHCR7 activity once cholesterol synthetic rates decrease postnatally. This case is a unique observation that underscores the adjunctive use of fibroblast and molecular testing in ambiguous cases of SLOS and may provide insight into the potential efficacy of therapeutic interventions altering postnatal cholesterol biosynthesis.
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mutations in the human sterol δ7 reductase gene at 11q12 13 cause smith lemli opitz Syndrome
American Journal of Human Genetics, 1998Co-Authors: Christopher A. Wassif, Robert D. Steiner, William E. Connor, Leesa M Linck, Don S Lin, Cheryl L Maslen, Stivelia Kachilelelinjewile, Forbes D PorterAbstract:Summary The Smith-Lemli-Opitz Syndrome (SLOS; also known as “RSH Syndrome” [MIM 270400]) is an autosomal recessive Multiple Malformation Syndrome due to a defect in cholesterol biosynthesis. Children with SLOS have elevated serum 7-dehydrocholesterol (7-DHC) levels and typically have low serum cholesterol levels. On the basis of this biochemical abnormality, it has been proposed that mutations in the human sterol D 7 -reductase (7-DHC reductase; E.C.1.3.1.21) gene cause SLOS. However, one could also propose a defect in a gene that encodes a protein necessary for either the expression or normal function of sterol D 7 -reductase. We cloned cDNA encoding a human sterol D 7 -reductase (DHCR7) on the basis of its homology with the sterol D 7 -reductase from Arabidopsis thaliana, and we confirmed the enzymatic function of the human gene product by expression in SLOS fibroblasts. SLOS fibroblasts transfected with human sterol D 7 -reductase cDNA showed a significant reduction in 7-DHC levels, compared with those in SLOS fibroblasts transfected with the vector alone. Using radiation-hybrid mapping, we show that the DHCR7 gene is encoded at chromosome 11q12-13. To establish that defects in this gene cause SLOS, we sequenced cDNA clones from SLOS patients. In three unrelated patients we have identified four different mutant alleles. Our results demonstrate both that the cDNA that we have identified encodes the human sterol D 7 -reductase and that
Ulrich Gembruch - One of the best experts on this subject based on the ideXlab platform.
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prenatal detection of fraser Syndrome without cryptophthalmos case report and review of the literature
Ultrasound in Obstetrics & Gynecology, 2001Co-Authors: C Berg, A Pertersenhansen, M Kochdorfler, Annegret Geipel, U Germer, Ulrich GembruchAbstract:Fraser Syndrome (cryptophthalmos–syndactyly Syndrome) is an autosomal recessive Multiple Malformation Syndrome whose major manifestations are cryptophthalmos, syndactyly, laryngeal atresia and urogenital defects. Enlarged hyperechogenic lungs contrasted by oligohydramnios, non-visualization of the kidneys and microphthalmia were sonographic markers leading to the prenatal detection of this rare autosomal recessive disorder in earlier reports. We report a case of Fraser Syndrome diagnosed at 16 weeks' gestational age in a woman whose previous pregnancy was terminated because of Multiple fetal Malformations. Abnormal sonographic findings included bilateral agenesis of the kidneys, dilated trachea and main bronchi (suggestive of high airway obstruction), hyperechogenic lungs, syndactyly of the fingers, hepatomegaly, oligohydramnios and hydrops placentae. Face and cerebral structures appeared normal. These findings together with those of the previously affected child led to the diagnosis of Fraser Syndrome. The parents elected to terminate the pregnancy. Autopsy results were confirmatory. In conclusion, prenatal diagnosis of Fraser Syndrome is possible in the hands of an expert, but due to the great variety of possible Malformations the diagnosis will remain doubtful in most cases in which no previous child is affected. Copyright © 2001 International Society of Ultrasound in Obstetrics and Gynecology
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p51prenatal detection of fraser Syndrome without cryptophthalmos
Ultrasound in Obstetrics & Gynecology, 2000Co-Authors: C Berg, Annegret Geipel, U Germer, Ulrich GembruchAbstract:Background Fraser Syndrome (cryptophthalmos–syndactyly Syndrome) is an autosomal recessive Multiple Malformation Syndrome whose major manifestations are cryptophthalmos, syndactyly, laryngeal atresia and urogenital defects. Enlarged hyperechogenic lungs contrasted by oligohydramnios, nonvisualization of the kidneys and microphthalmia were sonographic markers leading to the prenatal detection of this rare autosomal recessive disorder in earlier reports. Case report Fraser Syndrome was diagnosed at 16.0 weeks gestational age in a women whose previous pregnancy was terminated because of Multiple Malformations. Abnormal sonographic findings included agenesis of kidneys and bladder, dilated trachea and main bronchi suggestive for high airway obstruction, hyperechogenic lungs, syndactyly of the fingers, hepatomegaly, oligohydramnios and hydrops placentae. Strikingly, face and cerebral structures appeared normal. However these findings together with the previously affected child led to the diagnosis of Fraser Syndrome. The parents elected to terminate the pregnancy. Autopsy results were confirmatory. No defects of the face could be demonstrated. Conclusion Prenatal diagnosis of Fraser Syndrome is possible in the hands of an expert, but due to the great variety of possible Malformations the diagnosis will remain at doubt in most cases in which no previous child is affected.
R J Scott - One of the best experts on this subject based on the ideXlab platform.
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potter s Syndrome in the second trimester prenatal screening and pathological findings in 60 cases of oligohydramnios sequence
Prenatal Diagnosis, 1995Co-Authors: R J Scott, S F GoodburnAbstract:: Fifty-two second-trimester and eight third-trimester (> 28/40) autopsies with clinical or pathological evidence of oligohydramnios sequence ('Potter's Syndrome') were reviewed. Twenty-eight cases had renal anomalies (71 per cent in terminations following prenatal ultrasound), 27 had no renal Malformation (35 per cent with chorioamnionitis), and five had external assessments only. In 15 cases, the renal lesion was part of a Multiple Malformation Syndrome. Seven cases had a lesion which either recurred in a sibling in the same family or was a recognized autosomal recessive Syndrome. Three cases had an abnormal karyotype, two of which had renal anomalies. Maternal serum alpha-fetoprotein (AFP) did not discriminate between cases with renal Malformations and those without. Pulmonary hypoplasia was commoner in third-trimester than in second-trimester cases. External appearance and absent umbilical artery were not reliable predictors of underlying internal anomalies. These findings reflect the shift from postnatal to prenatal diagnosis in modern practice. In this series, mainly second-trimester cases, 50 per cent of cases had no Malformations, in a condition which is traditionally associated with renal disease. The high incidence of chorioamnionitis suggests that the mechanism of oligohydramnios is occult amniotic fluid leakage. Prenatal diagnosis of oligohydramnios in the second trimester is dependent on ultrasound scanning and a full post-mortem examination is necessary to identify any underlying fetal cause.
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potter s Syndrome in the second trimester prenatal screening and pathological findings in 60 cases of oligohydramnios sequence
Prenatal Diagnosis, 1995Co-Authors: R J Scott, S F GoodburnAbstract:Fifty-two second-trimester and eight third-trimester (> 28/40) autopsies with clinical or pathological evidence of oligohydramnios sequence ('Potter's Syndrome') were reviewed. Twenty-eight cases had renal anomalies (71 per cent in terminations following prenatal ultrasound), 27 had no renal Malformation (35 per cent with chorioamnionitis), and five had external assessments only. In 15 cases, the renal lesion was part of a Multiple Malformation Syndrome. Seven cases had a lesion which either recurred in a sibling in the same family or was a recognized autosomal recessive Syndrome. Three cases had an abnormal karyotype, two of which had renal anomalies. Maternal serum alpha-fetoprotein (AFP) did not discriminate between cases with renal Malformations and those without. Pulmonary hypoplasia was commoner in third-trimester than in second-trimester cases. External appearance and absent umbilical artery were not reliable predictors of underlying internal anomalies. These findings reflect the shift from postnatal to prenatal diagnosis in modern practice. In this series, mainly second-trimester cases, 50 per cent of cases had no Malformations, in a condition which is traditionally associated with renal disease. The high incidence of chorioamnionitis suggests that the mechanism of oligohydramnios is occult amniotic fluid leakage. Prenatal diagnosis of oligohydramnios in the second trimester is dependent on ultrasound scanning and a full post-mortem examination is necessary to identify any underlying fetal cause.
Han G Brunner - One of the best experts on this subject based on the ideXlab platform.
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ectodermal dysplasia cleft lip palate and severe cutaneous and osseous syndactyly in a mentally retarded girl a new Multiple Malformation Syndrome
American Journal of Medical Genetics, 1997Co-Authors: Hans Peter M Freihofer, Sajjad Walji, Han G BrunnerAbstract:A 13-year-old mentally retarded girl with severe cutaneous and osseous syndactyly of the hands and feet, cleft lip/palate, and ectodermal dysplasia is presented. We conclude that the pattern of Malformations described represents a new Multiple Malformation Syndrome. A comparison with Zlotogora-Ogur Syndrome is presented.
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ectodermal dysplasia cleft lip palate and severe cutaneous and osseous syndactyly in a mentally retarded girl a new Multiple Malformation Syndrome
American Journal of Medical Genetics, 1997Co-Authors: Hans Peter M Freihofer, Sajjad Walji, Han G BrunnerAbstract:A 13-year-old m entally retarded girl w ith se vere cu tan eou s and osseous syndactyly of the hands and feet, cleft lip/palate, and ec toderm al d ysp la sia is p resen ted . We con clude th at the pattern of m alform ations de scribed rep resen ts a n ew m ultiple m alfor m a tio n s y n d r o m e . A c o m p a r is o n w ith Zlotogora-Ogur syndrom e is presented. Am. J. Med. G enet. 70:211-215, 1997. 1997 W iley-Liss, Inc.