243whereas long-leggedness, small firm testes, gynecomastia, learning disabilities,
and moderate degree of spontaneous virilization suggest the diagnosis of hyper-
gonadotropic hypogonadism (Klinefelter’s syndrome). Further, the serum
gonadotropins are low or low normal in hypogonadotropic hypogonadism,
whereas both serum LH and FSH are elevated (FSH > LH) in hypergonado-
tropic hypogonadism.- How to suspect Klinefelter’s syndrome during early childhood?
Although there are no specific phenotypic features to diagnose KFS in new-
borns; clinodactyly, cleft palate, inguinal hernia, micropenis, and unde-
scended testis are more common in newborns with KFS. The clinical features
which suggest a diagnosis of Klinefelter’s syndrome in early childhood
include long- leggedness, docile behavior, developmental delay in speech,
and learning disabilities. Long-leggedness is usually apparent by the age of
5–8 years. Recognition of KFS in childhood is important because it may help
in appropriate management of learning disabilities at an earlier age and
timely initiation of testosterone therapy to prevent LH-mediated testicular
damage.- What is the trimodal presentation of KFS?
Majority of the patients with KFS (>75 %) are never diagnosed in their life-
time. Patients with KFS are commonly diagnosed during three phases of
life: incidentally during intrauterine period (prenatal karyotyping), in child-
hood with tall stature and learning disabilities, and in adulthood with
infertility.- How to explain the variability in phenotypic manifestations in patients with
Klinefelter’s syndrome?
Patients with classical KFS exhibit variability in phenotypic manifestations,
and this is possibly related to difference in number of CAG repeats in the
androgen receptor. Boys with KFS who have longer CAG repeats manifest
with late onset and slow progression of pubertal development, gynecomastia,
tall stature, low bone mineral density, and poor response to androgen replace-
ment. However, it has been shown that testicular degenerative process is rela-
tively slower in these subjects. Skewed inactivation of X chromosome was
also considered as a cause for variability in phenotypic manifestations; how-
ever, this hypothesis has been refuted in recent studies. In addition, patients
with mosaic Klinefelter’s syndrome may also have variable phenotypic mani-
festations (Fig. 7.15).
7 Delayed Puberty