Purpose: Simple virilizing congenital adrenal hyperplasia (SV-CAH) due to 21-hydroxylase deficiency (21-OHD) is an autosomal recessive disease caused by pathogenic variants of the CYP21A2 gene. Children with SV-CAH often experience delayed diagnosis, presenting with pseudo-precocious puberty in males and genital virilization in females. Genotyping is essential for diagnosis, treatment, optimization and phenotype prediction. This study describes the clinical and genetic characteristics of SV-CAH to guide treatment strategies.
Methods: From November 2016 to March 2023, 79 children (accounting for 34.3% of 230 CAH cases in the overall children's cohort) from 75 families were classified as SV-CAH due to 21-OHD at the Vietnam National Children's Hospital. Forty-three children underwent CYP21A2 mutation analysis using multiplex ligation-dependent probe amplification technique and complete gene sequencing to detect pathogenic variants.
Results: Median age at diagnosis was 4.5 years (IQR: 1 day – 22.3 years). There were 38.0% males and 62.0% females. Common symptom was penile enlargement in males (53.3%) and clitoromegaly (87.8%) in females; their height standard deviation (SD) at diagnosis was 1.90 ± 1.79 SD (-2.02 to +5.43) according to WHO; and bone age advancement was 4.65 ± 2.59 years. Genetic analysis identified 21 pathogenic variants and 22 genotypes in 43 children. The most common variant was p.I173N (47.7%); the most common genotype was p.I173N/p.I173N (16.3%).
Conclusion: Children with SV-CAH are often diagnosed late. Genetic analysis should be prioritized early, especially for children diagnosed through newborn screening programs. Determining the genotype is crucial for optimizing treatment strategies, ensuring personalized management, and avoiding overtreatment.
Keywords: 21-hydroxylase deficiency; Congenital adrenal hyperplasia; Simple virilizing.