The spectrum of clinical, hormonal and molecular findings in 280 individuals with nonclassical congenital adrenal hyperplasia caused by mutations of the CYP21A2 gene. (3rd August 2014)

• Record Type: Journal Article
• Authors: Livadas, S.; Dracopoulou, M.; Dastamani, A.; Sertedaki, A.; Maniati‐Christidi, M.; Magiakou, A.‐M.; Kanaka‐Gantenbein, C.; Chrousos, G.P.; Dacou‐Voutetakis, C.
• Is Part Of: Clinical endocrinology. Volume 82:Number 4(2015:Apr.)
• Page Start: 543
• Page End: 549
• Publication Date: 2014-08-03
• Subjects: Endocrinology -- Periodicals; 616.4005
• DOI: 10.1111/cen.12543
• Languages: English
• ISSNs: 0300-0664

Abstract

<abstract abstract-type="main" id="cen12543-abs-0001"> <title>Summary</title> <sec id="cen12543-sec-0001" sec-type="section"> <title>Background</title> <p>Nonclassical congenital adrenal hyperplasia (NC‐CAH) is caused by mutations of the <italic>CYP21A2</italic> gene. The clinical manifestations and hormonal derangements of NC‐CAH are quite variable.</p> </sec> <sec id="cen12543-sec-0002" sec-type="section"> <title>Objectives</title> <p>(i) To define the phenotype and its relation to genotype according to gender and age and (ii) to evaluate the validity of currently applied hormonal criteria for establishing the diagnosis of NC‐CAH.</p> </sec> <sec id="cen12543-sec-0003" sec-type="section"> <title>Patients and Methods</title> <p>The clinical, hormonal and molecular data of 280 subjects (235 female) with NC‐CAH and a median age of 17·6 years were analysed. <italic>CYP21A2</italic> genotyping was performed in all subjects.</p> </sec> <sec id="cen12543-sec-0004" sec-type="section"> <title>Results</title> <p>The majority of females aged less than 8 years presented with premature pubarche (88·3%), while those older than 8 presented with a polycystic ovary‐like phenotype (63·2%). A total of 7·7% of the females and 51·1% of the males were asymptomatic at the time of diagnosis. In the total group, 50·4% of the subjects were compound heterozygotes for one classical (C) and one nonclassical (NC) mutation, while 46% of the alleles studied carried the p.V281L mutation. Basal 17OHP values were below 6 n<sc>m</sc> (2 ng/ml) in 2·1% of the subjects with NC‐CAH, but none had peak 17OHP values post‐ACTH lower than 30 n<sc>m</sc> (10 ng/ml).</p> </sec> <sec id="cen12543-sec-0005" sec-type="section"> <title>Conclusions</title> <p>NC‐CAH has a variable phenotype depending on the age, gender and the presence of a classical mutation. A peak cut‐off value of 17OHP post‐ACTH lower than 30 n<sc>m</sc> excludes the diagnosis of NC‐CAH, whereas basal 17OHP <6 n<sc>m</sc> may represent a false‐negative result. A significant number of patients harboured a classical mutation, a finding which requires genotyping of the partner for genetic counselling.</p> </sec> </abstract>