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 and complete gene sequencing to detect pathogenic variants. Results: Median age at diagnosis was 4.5 years (interquartile range, 1 day–22.3 years). There were 38.0% males and 62.0% females. The most common symptoms were penile enlargement in males (53.3%) and clitoromegaly (87.8%) in females; the height standard deviation (SD) at diagnosis was 1.90±1.79 SD (-2.02 to 5.43) according to the World Health Organization; 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. To avoid that, early genetic analysis should be prioritized, especially for children diagnosed through newborn screening programs. Determining the genotype is crucial for optimizing treatment strategies, ensuring personalized management, and avoiding overtreatment.

Efonidipine, a calcium channel blocker, is widely used for the treatment of hypertension and cardiovascular diseases. In our preliminary study using structure-based virtual screening, efonidipine was identified as a potential inhibitor of c-Jun N-terminal kinase 3 (JNK3). Although its antihypertensive effect is widely known, the role of efonidipine in the central nervous system has remained elusive. The present study investigated the effects of efonidipine on the inflammation and cell migration induced by lipopolysaccharide (LPS) using murine BV2 and human HMC3 microglial cell lines and elucidated signaling molecules mediating its effects. We found that the phosphorylations of JNK and its downstream molecule c-Jun in LPS-treated BV2 cells were declined by efonidipine, confirming the finding from virtual screening. In addition, efonidipine inhibited the LPS-induced production of pro-inflammatory factors, including interleukin-1β (IL-1β) and nitric oxide. Similarly, the IL-1β production in LPS-treated HMC3 cells was also inhibited by efonidipine. Efonidipine markedly impeded cell migration stimulated by LPS in both cells. Furthermore, it inhibited the phosphorylation of inhibitor kappa B, thereby suppressing nuclear translocation of nuclear factor-κB (NF-κB) in LPS-treated BV2 cells. Taken together, efonidipine exerts anti-inflammatory and anti-migratory effects in LPS-treated microglial cells through inhibition of the JNK/NF-κB pathway. These findings imply that efonidipine may be a potential candidate for drug repositioning, with beneficial impacts on brain disorders associated with neuroinflammation.