title: Five patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency (one with associated neuroblastoma) discovered in three generations of one family.
abstract: BACKGROUND
  Most patients with 21-hydroxylase deficiency (21-OHD) are compound heterozygous carriers. Their phenotype usually reflects a less severe allelic mutation, although discordance between the genotype and the phenotype has been observed.
  
  
  METHODS
  We present 5 patients with congenital adrenal hyperplasia (CAH) due to 21-OHD belonging to the 3 generations of the same family (grandmother, parents and their 2 children). As each patient carries at least one mild mutation of the CYP21 gene, their genotypes correspond to nonclassical CAH. The propositus is the older brother, who is compound heterozygous with a mild and severe CYP21 mutation (P30L/R356W). In spite of one mild CYP21 mutation, he presented with the clinical picture of a simple virilizing form of 21-OHD and required glucocorticoid replacement therapy from the age of 4. Both probands' parents are compound heterozygous carriers of different CYP21 gene mutations causing various degrees of enzymatic activity impairment, which explains the different genotypes and phenotypes in their offspring. The probands' mother, besides the nonclassical 21-OHD, also had neuroblastoma of the adrenal gland.
  
  
  CONCLUSIONS
  The potential discordance between the genotype and the phenotype in some patients with CAH is emphasized. The existence of a mild CYP21 mutation P30L in a compound heterozygous with CAH might be associated with progressive virilization requiring glucocorticoid therapy from early childhood. The occurrence of neuroblastoma with 21-OHD may support the hypothesis that an impairment in the synthesis and secretion of glucocorticoids may play role in the development and functioning of the adrenal medulla.
authors.affiliation: Department of Pediatrics, University Hospital Center Zagreb, Zagreb, Croatia.
authors.forename: Nevena
authors.initials: N
authors.lastname: Janjanin
authors.forename: Miroslav
authors.initials: M
authors.lastname: Dumic
authors.forename: Veselin
authors.initials: V
authors.lastname: Skrabic
authors.forename: Vesna
authors.initials: V
authors.lastname: Kusec
authors.forename: Zorana
authors.initials: Z
authors.lastname: Grubic
authors.forename: Anita
authors.initials: A
authors.lastname: Spehar Uroic
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000150:complications*; D000312:Adrenal Hyperplasia, Congenital / Q000150:complications / Q000175:diagnosis*; D000328:Adult; D002675:Child, Preschool; D005190:Family; D005191:Family Characteristics; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009447:Neuroblastoma / Q000150:complications*; D010375:Pedigree; D013255:Steroid 21-Hydroxylase
chemical_list: D013255:Steroid 21-Hydroxylase