Congenital Adrenal Hyperplasia – A Comprehensive Review of Genetic Studies on 21-Hydroxylase Deficiency from India

Abstract

Abstract Congenital adrenal hyperplasia (CAH) comprises a heterogeneous group of autosomal recessive disorders impairing adrenal steroidogenesis. Most cases are caused by mutations in the CYP21A2 gene resulting in 21-hydroxylase (21-OH) deficiency (21-OHD). The genetics of 21-OH CAH is complexed by a highly homologous pseudogene CYP21A1P imposing several limitations in the molecular analysis. Therefore, genetic testing is still not a part of routine CAH diagnosis and is mainly dependent on 17-hydroxy progesterone (OHP) measurements. There are very few reports of CYP21A2 gene analysis from India and there is no comprehensive review available on genetic testing and the spectrum of CYP21A2 mutations from the country. This review focuses on the molecular aspects of 21-OHD and the genetic studies on CYP21A2 gene reported from India. The results of these studies insist the compelling need for large-scale CYP21A2 genetic testing and newborn screening (NBS) in India. With a high disease prevalence and consanguinity rates, robust and cost-effective genetic testing for 21-OH CAH would enable an accurate diagnosis in routine clinical practice. Whereas establishing affordable genotyping assays even in secondary care or resource-poor settings of the country can identify 90% of the mutations that are pseudogene derived, initiatives on reference laboratories for CAH across the nation with comprehensive genetic testing facilities will be beneficial in those requiring extended analysis of CYP21A2 gene. Further to this, incorporating genetic testing in NBS and carrier screening programmes will enable early diagnosis, better risk assessment and community-based management.