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Genetics of congenital adrenal hyperplasia and genotype-phenotype correlation. Narasimhan Mithra L,Khattab Ahmed Fertility and sterility Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is caused by mutations in the CYP21A2 gene, located on the short arm of chromosome 6. The two main underlying mechanisms of CYP21A2 defects are large gene deletion and conversion. Anticipation of the phenotypes associated with different combinations of CYP21A2 mutations remains the most important determinant in prenatal diagnosis and counseling of the expectant couple who are determined to be at risk for congenital adrenal hyperplasia. 10.1016/j.fertnstert.2018.11.007
Prenatal genetic testing and treatment for congenital adrenal hyperplasia. Simpson Joe Leigh,Rechitsky Svetlana Fertility and sterility Couples at risk for autosomal recessive congenital adrenal hyperplasia often request anticipatory guidance and genetic counseling. Initially, hormones in amniotic fluid were measured to distinguish affected female fetuses from unaffected fetuses. With the molecular era, more-targeted approaches became possible. Prenatal genetic diagnosis via amniocentesis or chorionic villus sampling was used to determine the need for continuing fetal therapy (dexamethasone), allowing cessation if the fetus was unaffected. Newer methods now allow diagnosis earlier in gestation, further shortening the treatment time for unaffected female fetuses who will not develop genital ambiguity. Preimplantation genetic testing permits transfer only of an unaffected female or male fetus. Analysis of maternal cell-free DNA based on quantitative differences in the amount of allele parental DNA permits affected pregnancies to be differentiated from unaffected pregnancies. 10.1016/j.fertnstert.2018.11.041
Preventing female virilisation in congenital adrenal hyperplasia: The controversial role of antenatal dexamethasone. Heland Sarah,Hewitt Jacqueline K,McGillivray George,Walker Susan P The Australian & New Zealand journal of obstetrics & gynaecology Congenital adrenal hyperplasia (CAH) refers to a group of recessively inherited disorders of cortisol production, which in the classical form results in virilisation of female fetuses. Since the 1980s, antenatal treatment with dexamethasone has been recommended in high-risk pregnancies to minimise the risk of virilising the female genitalia of affected fetuses. To be effective, this treatment requires implementation in early pregnancy, prior to the commencement of autonomous fetal adrenal androgen synthesis. Using this approach, seven of eight high-risk pregnancies are treated unnecessarily, prior to establishing the fetal gender or the confirmed diagnosis of a genetically affected pregnancy. In the face of ongoing concerns regarding potential adverse maternal-fetal effects of antenatal dexamethasone exposure, a review of this practice has been advocated by expert advisory groups. In this review, we summarise current controversies, potential improvements and future directions in the management of pregnancies at risk of CAH. In high-risk families, recent genomic advances include early prenatal diagnosis utilising noninvasive genetic techniques to minimise unnecessary dexamethasone exposure to unaffected fetuses. In affected pregnancies when families elect for antenatal treatment, optimal antenatal dosing regimens need to be defined and a standardised treatment and follow-up protocol are recommended. Establishment of a national registry with standardised follow-up will allow future families to be better informed of the risks and benefits of both treated and untreated fetal CAH. 10.1111/ajo.12423