Premature pubarche in Mediterranean girls: high prevalence of heterozygous CYP21 mutation carriers.
OBJECTIVE
This study investigated the prevalence and consequences of heterozygous CYP21A2 mutations in premature pubarche (PP) girls.


RESULTS
We investigated 36 French Mediterranean girls with isolated PP. We performed synacthen testing with 17OHP and 21-deoxycortisol evaluation, along with molecular analysis of the CYP21A2 gene in girls with abnormal elevation of one of these two adrenal steroids. Three girls (8.3%) had nonclassical adrenal hyperplasia, secondary to compound heterozygosity that associated at least one severe mutation for the three girls. A heterozygous mutation of the CYP21A2 gene was confirmed by molecular biology in eight girls (22%); a deletion of the CYP21A2 gene was found in one of them. Biological hyperandrogenism was found in the prepubertal CYP21A2 mutation carriers, whereas the four heterozygous girls who were followed long enough to have reached pubertal age presented biological and clinical hyperandrogenism.


CONCLUSIONS
We underline the high prevalence of heterozygous CYP21A2 mutations in girls with PP and demonstrate the usefulness of systematic screening by synacthen testing, both to improve their future clinical management and to prevent the transmission of classical adrenal hyperplasia to future offspring. Because of the severe metabolic and cardiovascular consequences of hyperandrogenism, long-term follow-up of these heterozygous patients is mandatory.
Paris
Françoise
F
Unité d'Endocrinologie Pédiatrique, Hôpital Arnaud de Villeneuve, CHU-Montpellier et UM1, Montpellier, France.
Tardy
Véronique
V
Chalançon
Anne
A
Picot
Marie Christine
MC
Morel
Yves
Y
Sultan
Charles
C
D019326:17-alpha-Hydroxyprogesterone / Q000097:blood; D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D003350:Cortodoxone / Q000097:blood; D003366:Cosyntropin; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood; D005260:Female; D005602:France; D006579:Heterozygote; D006801:Humans; D017588:Hyperandrogenism / Q000235:genetics; D019083:Mediterranean Region; D009154:Mutation / Q000235:genetics*; D011629:Puberty, Precocious / Q000097:blood / Q000235:genetics*; D013255:Steroid 21-Hydroxylase / Q000235:genetics*; D013739:Testosterone / Q000097:blood
D003366:Cosyntropin; D013739:Testosterone; D019314:Dehydroepiandrosterone Sulfate; C003556:21-deoxycortisol; D019326:17-alpha-Hydroxyprogesterone; C531510:CYP21A2 protein, human; D013255:Steroid 21-Hydroxylase; D003350:Cortodoxone