A multicenter study of women with nonclassical congenital adrenal hyperplasia: Relationship between genotype and phenotype

Characteristic presentation of nonclassical adrenal hyperplasia (NCAH) due to 21-hydroxylase deficiency was compared between women carrying a severe a nd a mild CYP21 mutation (Group 1, N = 26) versus homozygotes for mild muta tions (Group 2, N = 8). The diagnosis was based on elevated ACTH-stimulated 17OH-progesterone (17OHP). Genotyping for 10 mutations was performed by PC R-based techniques. Jewish patients predominated among Group 2 (25% vs 11.5 % in Group 1); however, 85% of all patients were non-Jewish Caucasians. Ave rage age of presentation was 23-25 years, and did not differ between groups . Hirsutism, and to a lesser extent oligomenorrhea and acne, were more prev alent among Group 1 women. There was a trend to higher basal 17OHP among Gr oup 1 patients (mean +/- SEM; 1354 +/- 323 vs 714 +/- 129 ng/dl, P less tha n or equal to 0.25). The lack of significant difference was perhaps due to the relatively few homozygotes for 2 mild mutations (24%). V281L was carrie d on similar to 48% of all alleles, and about 16% carried either P30L or P4 53S. Approximately 38% of alleles and 77% of patients carried a classic mut ation. These data have important implications for genetic counseling. In su mmary, we describe differences in clinical, hormonal, and genetic character istics among a multiethnic group of females with NCAH. (C) 2000 Academic Pr ess.