Genetics, Hormonal, and Genital Features of Congenital Adrenal Hyperplasia Patients In Semarang

Abstract

Congenital Adrenal Hyperplasia (CAH) is a familial disorder derived from reduction activity of enzymes in steroidogenesis process of the adrenal cortex that caused by a mutation of CYP21 gene located at 6p21.3. Prominent manifestation of CAH patients is ambiguity on their genitalia. This was a descriptive observational retrospective and prospective study following genetics, hormonal, and genital features from subjects with suspected CAH. Data was obtained using medical records from the Molecular and Cytogenetic Unit in Faculty of Medicine Diponegoro University and cytogenetic laboratory of Telogorejo hospital in Semarang since April 2004 to April 2005. Of the 79 patients diagnosed as ambiguous genitalia and hypospadia, 17 patients were suspected CAH and three of them were with mental retardation. Mutation analysis of CYP21 gene was done for 11 (64,7%) patients. Of the 8 cases (72,7%) depicted common homozygous mutations (i.e. 163 bp del, IVS2-13A>G, K102R, S493N, I172N, R356W, S268T), 6 cases (75%) demonstrated other common heterozygote mutation. Interestingly, 3 patients had heterozygous mutations (i.e. one patient with heterozygote Q318X, one with heterozygote V281L+920-921insT+Q381X and the other had heterozygote mutations I172N + R356 W all in 1 allele) manifested as simple virilizing CAH. The most frequent mutations were S493N (20%) followed by IVS2-13A>G (15%) and I172N, R356W (14%) respectively. These frequencies are rather different than other published data in Caucasian population. Among those cases were found two familial cases, patients with suspect adrenal tumours, aromatase deficiency and glucocorticoid receptor defect. Only 8 patients (47%) had specific hormonal values for CAH. Clinical stigmata were varies, however all patients developed enlarged clitoris. Establishing physical examination alone is not effective in diagnosing CAH. Cytogenetic, hormonal assay and mutation analysis are essential for assessments. Keywords : ambiguous genitalia, congenital adrenal hyperplasia, CAH, CYP21 gene