The history of prenatal diagnosis of congenital adrenal hyperplasia

Maria I. New, Dennis Lo

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review


Congenital adrenal hyperplasia (CAH) owing to 21-hydroxylase deficiency (21OHD) is a disorder of adrenal steroidogenesis, which causes virilization of external genitalia in females affected with the severe form of the disease. However, genital ambiguity is preventable with prenatal treatment with dexamethasone during the first trimester. While prenatal treatment has remained largely unchanged since its institution, prenatal diagnosis of CAH has witnessed a number of advancements in the past 50 years. The first successful prenatal diagnosis utilized hormonal measurements of the amniotic fluid. Elevated levels of 17α-hydroxyprogesterone in the amniotic fluid became diagnostic for a fetus affected with the severe form of the disorder. This finding was followed by the discovery of the close linkage between the disease and the HLA complex, which led to HLA linkage studies as a second approach for prenatal diagnosis. Cloning of the CYP21A2 gene ushered in molecular genetic analysis as the third method for prenatal diagnosis. Using polymerase chain reaction (PCR)-based methods to amplify the CYP21A2 active gene, and not the CYP21A1P pseudogene, diagnostic procedures increased in specificity and led to accurate prenatal diagnosis in the first trimester. The advent of noninvasive prenatal diagnosis heralds a new development for prenatal diagnosis of CAH, with the potential for improved safety, earlier detection, and increased accessibility.

Original languageEnglish
Title of host publicationGenetic Steroid Disorders
Subtitle of host publicationSecond Edition
Number of pages11
ISBN (Electronic)9780128214244
ISBN (Print)9780128214251
StatePublished - 1 Jan 2023


  • 21-hydroxylase deficiency
  • Congenital adrenal hyperplasia
  • fetal sex determination
  • prenatal diagnosis


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