title: The spectrum of clinical, hormonal and molecular findings in 280 individuals with nonclassical congenital adrenal hyperplasia caused by mutations of the CYP21A2 gene.
abstract: BACKGROUND
  Nonclassical congenital adrenal hyperplasia (NC-CAH) is caused by mutations of the CYP21A2 gene. The clinical manifestations and hormonal derangements of NC-CAH are quite variable.
  
  
  OBJECTIVE
  (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.
  
  
  METHODS
  The clinical, hormonal and molecular data of 280 subjects (235 female) with NC-CAH and a median age of 17·6 years were analysed. CYP21A2 genotyping was performed in all subjects.
  
  
  RESULTS
  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 nm (2 ng/ml) in 2·1% of the subjects with NC-CAH, but none had peak 17OHP values post-ACTH lower than 30 nm (10 ng/ml).
  
  
  CONCLUSIONS
  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 nm excludes the diagnosis of NC-CAH, whereas basal 17OHP <6 nm 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.
authors.affiliation: First Department of Pediatrics, Division of Endocrinology, Diabetes and Metabolism, School of Medicine, "Aghia Sophia" Children's Hospital, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: S
authors.initials: S
authors.lastname: Livadas
authors.forename: M
authors.initials: M
authors.lastname: Dracopoulou
authors.forename: A
authors.initials: A
authors.lastname: Dastamani
authors.forename: A
authors.initials: A
authors.lastname: Sertedaki
authors.forename: M
authors.initials: M
authors.lastname: Maniati-Christidi
authors.forename: A-M
authors.initials: AM
authors.lastname: Magiakou
authors.forename: C
authors.initials: C
authors.lastname: Kanaka-Gantenbein
authors.forename: G P
authors.initials: GP
authors.lastname: Chrousos
authors.forename: C
authors.initials: C
authors.lastname: Dacou-Voutetakis
mesh_terms: D000293:Adolescent; D000312:Adrenal Hyperplasia, Congenital / Q000235:genetics*; D000328:Adult; D000368:Aged; D000483:Alleles; D002648:Child; D002675:Child, Preschool; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D011085:Polycystic Ovary Syndrome / Q000503:physiopathology; D013255:Steroid 21-Hydroxylase / Q000235:genetics*; D055815:Young Adult
chemical_list: C531510:CYP21A2 protein, human; D013255:Steroid 21-Hydroxylase