The prevalence of precocious puberty is higher in certain ethnic groups, and some cases may be familial. The aim of this study was to investigate the mode of inheritance of familial precocious puberty and to identify characteristics that distinguish familial from isolated precocious puberty. Of the 453 children referred to our center for suspected precocious puberty between January 1, 1997, and December 31, 2000, 156 (147 girls and 9 boys) were found to have idiopathic central precocious puberty, which was familial in 43 (42 girls and 1 boy) (27.5%). Data of the familial and sporadic cases were compared. The familial group was characterized by a significantly lower maternal age at menarche than the sporadic group (mean, 11.47 +/- 1.96 vs. 12.66 +/- 1.18 yr; P = 0.0001) and more advanced puberty at admission (Tanner stage 2, 56.5% vs. 78.1%; P = 0.006). Segregation analysis was used to study the mode of inheritance. The segregation ratio for precocious puberty was 0.38 (0.45 after exclusion of young siblings) assuming incomplete penetrance and 0.58 (0.65 after exclusion of young siblings) assuming complete ascertainment. These results suggest autosomal dominant transmission with incomplete, sex-dependent penetrance.

Prolonged administration of 200 micrograms of inhaled budesonide daily to young children with severe asthma does not impair growth or pituitary-adrenal function.

Objective: To evaluate whether genotype differences can explain the clinical variability of non-classical steroid 21-hydroxylase de®ciency (NC21-OHD) and to determine if genotype is related to ethnic origin. Design: Genotyping for mutations in the steroid 21-hydroxylase (CYP21) gene was performed in 45 unrelated Israeli Jewish patients (nine males) with NC21-OHD (60 min 17-hydroxyprogesterone (17-OHP), 45±386 nmol/l) who were referred for evaluation of postnatal virilization or true precocious/ early puberty. Eleven siblings diagnosed through family screening were genotyped as well. Methods: Patients were divided by genotype into three groups: (A) homozygous or compound heterozygous for the mild mutations (V281L or P30L) (n=29; eight males); (B) compound heterozygous for one mild and one severe mutation (Q318X, I2 splice, I172N) (n=12; no males); (C) mild mutation detected on one allele only (n=4; one male; peak 17-OHP 58±151 nmol/l). We then related the genotype to the ethnic origin, clinical phenotype and hormone level. Since group C was very small, comparisons were made between groups A and B only. Results: At diagnosis, group B tended to be younger (5.863.0 vs 8.164.3 years, P 0.09), had greater height SDS adjusted for mid-parental height SDS (1.661.1 vs 0.761.4, P 0.034), tended to have more advanced bone age SDS (2.961.5 vs 1.762.1, P 0.10) and had a higher peak 17-OHP level in response to ACTH stimulation (226692 vs 126662 nmol/l, P < 0.01). Group B also had pubarche and gonadarche at an earlier age (5.162.4 vs 7.462.2 years, P < 0.01 and 7.461.8 vs 9.961.4 years, P < 0.001, respectively) and a higher rate of precocious puberty (50 vs 17%, P 0.04). Stepwise logistic regression analysis (excluding males) yielded age at gonadarche as the most signi®cant variable differentiating the two groups, with a positive predictive value of 86% for a cut-off of 7.5 years. Conclusions: The ®ndings suggest that genotype might explain some of the variability in the phenotypic expression of NC21-OHD. Compound heterozygotes for one mild and one severe mutation have a higher peak 17-OHP associated with pubarche and gonadarche at an earlier age and more frequent precocious puberty. Hence, the severity of the enzymatic defect might determine the timing and pattern of puberty.

The GnRH-agonist test and the repeated-injection hCG test are reliable diagnostic tools for differentiating CDP from GD in boys.