Long-Term Outcome in Offspring and Mothers of Dexamethasone-Treated Pregnancies at Risk for Classical Congenital Adrenal Hyperplasia Owing to 21-Hydroxylase Deficiency - GSD 5610
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PROVIDER: PRJNA377385 | ENA |
REPOSITORIES: ENA
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Project description:<p><i>Summary</i></p> <p>The purpose of this study is to perform the first long-term follow up study both of adolescents and young adults with a history of prenatal treatment with dexamethasone and of their mothers and to test for adverse medical or behavioral side effects. The emphasis will be on the outcome of this prenatal treatment in those fetuses who are not affected with steroid 21-hydroxylase deficiency (21OHD) form of congenital adrenal hyperplasia (CAH) and are either heterozygotes or homozygote-unaffected.</p> <p>Prenatal treatment of 46,XX fetuses with 21OHD (via administration of dexamethasone to the pregnant mother) has been shown to reduce the masculinization of the genitalia and, thereby, the later need for 'corrective' feminizing genital surgery and potential impairment of sexual functioning. Along with the suppression of excess prenatal androgen production and reduction of prenatal masculinization of the genitalia in 46,XX fetuses with 21OHD, prenatal dexamethasone treatment may reduce the behavioral masculinization that is well documented in untreated 46, XX patients with 21OHD. Those fetuses who are partially treated until diagnosis of an unaffected status (heterozygous or homozygous-unaffected) will be studied as well. This latter group is of importance because these fetuses are being unnecessarily treated, but we have no way of diagnosing the unaffected status before the 8th week of gestation when treatment must begin for the female fetus who is affected. As treatment is necessary only until term in the female fetus affected with classical CAH, male fetuses and unaffected or heterozygous female fetuses do not require treatment. Thus, only one out of eight fetuses will require prenatal treatment until term. Findings of adverse effects of glucocorticoid treatment in non-human mammals [1, 2] have raised concerns among other clinicians and investigators about potential adverse side effects of such treatment on the developing human. Thus, this study will address this concern and investigate the potential adverse side effects of prenatal treatment.</p> <p><i>Detailed Description </i></p> <p>Females with classical CAH owing to 21-hydroxylase deficiency are born with ambiguous genitalia due to the production of excess androgens in utero. Prenatal treatment with dexamethasone was inaugurated in 1978 by Maguelone Forest and has been the standard of practice in the United States since 1986. Dexamethasone, which crosses the placental barrier, suppresses the fetal adrenal gland production of androgens, thus preventing ambiguous genitalia in the affected female. Children of both sexes are prenatally treated as soon as pregnancies at risk are confirmed. Treatment in females with 21OHD continues to term, but is discontinued in males and unaffected females. To date, 685 pregnancies have been diagnosed, of which 366 fetuses were treated. These investigators will study prenatally treated adolescents and adults 12 years and older with respect to medical and behavioral outcomes (see Table 5). In addition, mothers of children prenatally treated for varying periods of time for suspected 21OHD will be studied for long-term side effects of dexamethasone treatment administered during pregnancy. The long-term outcome in these children and their mothers has never before been studied.</p>
| phs001317 | dbGaP
Project description:Modifier Genes in 21-hydroxylase Deficiency - GSD 5607
| PRJNA377375 | ENA
Project description:Long-Term Outcome in Offspring and Mothers of Dexamethasone-Treated Pregnancies at Risk for Classical Congenital Adrenal Hyperplasia Owing to 21-Hydroxylase Deficiency - GSD 5610
| PRJNA377386 | ENA
Project description:ObjectivesTo test whether dexamethasone (DEX) treatment in pregnancies at risk for congenital adrenal hyperplasia (CAH) impairs cognitive functioning in the offspring.DesignObservational follow-up of prenatally DEX-exposed offspring and controls.MethodsStudy 1 included 140 children aged 512 years: 67 DEX-exposed (long-term: eight CAH girls) and 73 unexposed (with 15 CAH girls). Study 2 included 20 participants aged 11-24 years: seven DEX-exposed (long-term: one CAH woman) and 13 unexposed (with four CAH women). Neuropsychological testing was done in hospital settings or at patients' homes. Data analysis aimed at maximizing detection of the effects of DEX exposure.ResultsThe vast majority of group comparisons were not marginally or conventionally significant. The few significant findings on short-term prenatal DEX exposure suggested more positive than adverse outcomes. By contrast, few significant findings in females with CAH and long-term DEX exposure indicated slower mental processing than in controls on several neuropsychological variables, although partial correlations of DEX exposure duration with cognitive outcome did not corroborate this association.ConclusionsAlthough our studies do not replicate a previously reported adverse effect of short-term prenatal DEX exposure on working memory, our findings on cognitive function in CAH girls with long-term DEX exposure contribute to concerns about potentially adverse cognitive after effects of such exposure. Yet, our studies are not definitive, and replications in larger samples are required.
| S-EPMC3383400 | biostudies-literature
Project description:Fetal progenitor endothelial cells (endothelial colony forming cells; ECFC) are recruited for repair, vascular growth and angiogenesis and their high abundance perinatally suggests a function in postnatal vasculogenesis and angiogenesis. In this study we profiled ECFCs from pregnancies of control, overweight and diabetic mothers to study if adverse pregnancies are associated with epigenetic variation in ECFCs.
2021-12-14 | GSE180355 | GEO
Project description: Not available
| S-EPMC4428642 | biostudies-literature
Project description:Substantial research has been performed during the last decades on the clinical and genetic variability of congenital adrenal hyperplasia (CAH) and its most common form, 21-hydroxylase deficiency (21OHD). CAH is one of the most prevalent autosomal recessive diseases in humans, and it can be divided into classic-further subdivided into salt wasting (SW) and simple virilizing (SV)-and non-classic (NC) forms. Pathogenic variants of CYP21A2 gene, encoding the 21-hydroxylase enzyme, have been reported with variable prevalence in different populations. NM_000500.9:c.293-13C/A>G (In2G) variant represents the most common CYP21A2 gene changes related to the classic 21OHD form. However, the phenotype of In2G carriers is variable depending on the variant homozygous/heterozygous status and combination with other CYP21A2 pathogenic variants. In addition, identical genotypes, harboring the homozygous In2G variant, can present with variable phenotypes including the SW and SV or rarely NC form of the disease. Here, we analyze and present the clinical aspects, genotype/phenotype correlations, and other characteristics related to the CYP21A2 In2G variant.
| S-EPMC8818746 | biostudies-literature
Project description:BackgroundCongenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders caused by defects in the steroid 21 hydroxylase gene (CYP21A2). We studied the spectrum of mutations in CYP21A2 gene in a multi-ethnic population in Pakistan to explore the genetics of CAH.MethodsA cross sectional study was conducted for the identification of mutations CYP21A2 and their phenotypic associations in CAH using ARMS-PCR assay.ResultsOverall, 29 patients were analyzed for nine different mutations. The group consisted of two major forms of CAH including 17 salt wasters and 12 simple virilizers. There were 14 phenotypic males and 15 females representing all the major ethnic groups of Pakistan. Parental consanguinity was reported in 65% cases and was equally distributed in the major ethnic groups. Among 58 chromosomes analyzed, mutations were identified in 45 (78.6%) chromosomes. The most frequent mutation was I2 splice (27%) followed by Ile173Asn (26%), Arg 357 Trp (19%), Gln319stop, 16% and Leu308InsT (12%), whereas Val282Leu was not observed in this study. Homozygosity was seen in 44% and heterozygosity in 34% cases. I2 splice mutation was found to be associated with SW in the homozygous. The Ile173Asn mutation was identified in both SW and SV forms. Moreover, Arg357Trp manifested SW in compound heterozygous state.ConclusionOur study showed that CAH exists in our population with ethnic difference in the prevalence of mutations examined.
| S-EPMC3050769 | biostudies-literature
Project description:21-Hydroxylase Deficiency (21-OH Deficiency) represents the most common form of Congenital Adrenal Hyperplasia (CAH), a complex and heterogenous group of conditions, characterised by defects in one of the five enzymes involved in adrenal steroidogenesis. Defects in this steroidogenic enzyme, the product of the CYP21A2 gene, cause disruption in the pathway involved in cortisol and aldosterone production and consequently, the accumulation of their steroid precursors as well as a resulting adrenocorticotrophic hormone (ACTH)-driven overproduction of adrenal androgens. Treatment with glucocorticoid, with or without mineralocorticoid and salt replacement, is directed at preventing adrenal crises and ensuring normal childhood growth by alleviating hyperandrogenism. Conventionally, two clinical forms of 21-OH Deficiency are described - the classical form, separated into salt-wasting and simple-virilising phenotypes, and the non-classical form. They are differentiated by their hormonal profile, predominant clinical features and age of presentation. A greater understanding of the genotype-phenotype correlation supports the view that 21-OH Deficiency is a continuum of phenotypes as opposed to a number of distinct phenotypical entities. Significant advancements in technologies such as Tandem Mass Spectrometry (TMS) and improvements in gene analysis, such as complete PCR-based sequencing of the involved gene, have resulted in remarkable developments in the areas of diagnosis, treatment and treatment monitoring, neonatal screening, prenatal diagnosis and prenatal therapy.
| S-EPMC2702216 | biostudies-literature