Impact of body mass index on growth in boys with delayed puberty.

It is unclear whether overweight but otherwise healthy boys with delayed puberty have a variation of constitutional delay of growth and maturation (CDGM) or a different etiology for their pubertal delay. To characterize better this group of boys and investigate whether their growth pattern distinguishes them from boys with typical CDGM, growth data were analyzed in eight overweight (BMI SDS > or = 85th percentile) and 37 non-overweight (BMI SDS <85th percentile) boys with delayed puberty. Primary outcome measures included predicted height (PH) and adult height (AH).

Determination of sequence variation and haplotype structure for the gonadotropin-releasing hormone (GnRH) and GnRH receptor genes: investigation of role in pubertal timing.

Because GnRH and its receptor (GnRHR) are pivotal regulators of the reproductive endocrine axis and mutations in GNRHR lead to hypogonadotropic hypogonadism, we investigated whether genetic variation in GNRHR or GNRH1 affects pubertal timing in the general population. To screen for missense mutations in these genes that might affect pubertal timing, we resequenced the coding regions of these genes in 48 probands with late but otherwise normal pubertal development. No missense variants were found in either gene, except for a previously identified single nucleotide polymorphism (SNP) in GNRH1 that was not associated with late pubertal development.

Pedigree analysis of constitutional delay of growth and maturation: determination of familial aggregation and inheritance patterns.

To investigate the genetic basis of constitutional delay of growth and maturation (CD), 41 families of CD probands underwent interviews regarding pubertal timing, and 12 additional families had history data analyzed from medical records. The family histories of the 53 probands (40 boys and 13 girls) were assessed for pubertal delay using both strict criteria (pubertal delay >or=2 SD beyond the mean) and relaxed criteria (pubertal delay >or=1 SD beyond the mean). These pedigrees were compared with 25 control pedigrees.

Delayed puberty: analysis of a large case series from an academic center.

Despite the clinical importance of delayed puberty, the understanding of this condition is hampered by the lack of studies evaluating etiologies and predisposing factors among large case series. We performed a retrospective study of clinical and laboratory data from adolescents (< or =18 yr of age) with delayed puberty who had been seen in our clinic between 1/96 and 7/99 (n = 232 subjects; 158 males and 74 females). Family histories of pubertal timing among primary relatives were classified as negative, having at least a tendency to pubertal delay (development > or =1 SD beyond the mean), or diagnostic of delay (development > or =2 SD beyond the mean).