Endocrine Abstracts

JOINT627

Introduction: Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders caused by mutations in genes involved in cortisol biosynthesis, most commonly CYP21A2. Genetic testing has become integral in confirming diagnoses, and guiding management.

Objective: To assess the prevalence of genetic mutations, evaluate the diagnostic and clinical value, and analyze the reliability of various genetic testing methods in CAH.

Methods: A comprehensive review of published studies (2015–2025) was conducted, focusing on the prevalence of CAH-related genetic variations and the utility of testing in diagnosis and management.

Results: 1. Prevalence:

• Genetic mutations linked to CAH were frequently detected, with large-scale studies reporting a positive genetic result in more than 60% of clinically suspected cases. The prevalence of specific syndromes, such as CAH-X, was estimated at approximately 10%, emphasizing the role of genetic testing in identifying rare forms of the disorder.

• Copy number variations, point mutations, and deletions in the CYP21A2 gene were the most commonly reported abnormalities, contributing to the phenotypic variability observed in CAH patients.

2. Value of Genetic Testing:

• Genetic testing plays a critical role in confirming CAH diagnoses, reclassifying patient phenotypes, and guiding personalized treatment strategies. Studies highlighted its utility in avoiding severe complications through early diagnosis and effective management.

• Techniques such as multiplex ligation-dependent probe amplification (MLPA), Sanger sequencing, and next-generation sequencing (NGS) provided detailed insights into the genetic landscape of CAH, enabling better understanding of genotype-phenotype correlations.

• Advanced molecular strategies facilitated the identification of novel mutations and improved diagnostic accuracy, particularly in complex or atypical cases.

3. Reliability:

• High levels of accuracy were reported for commonly used methods, with detection rates of 89–95% for point mutations and deletions.

• Techniques like MLPA and long-read sequencing demonstrated strong performance in identifying both common mutations and large gene rearrangements.

• The reliability of genetic testing was further enhanced by combining multiple methodologies, addressing challenges such as pseudogene interference and genetic complexity.

• Emerging technologies, including MinION-based sequencing, offered rapid, cost-effective alternatives with comparable accuracy, making them promising tools for routine clinical use.

Conclusion: Genetic testing is a cornerstone of CAH diagnosis and management, providing essential data on mutation prevalence, phenotype reclassification, and therapeutic guidance. Its high reliability and the availability of advanced testing methods reinforce its value in clinical settings. Future directions should focus on integrating cutting-edge technologies into routine diagnostics and enhancing accessibility to improve CAH outcomes.