Of note, the X-linked form of Kallmann syndrome (KS) form of GnRH insensitivity relating to mutations in the ANOS1 gene has the most consistent severe phenotypic presentation (i.e., prepubertal testes size and complete absence of gonadotropin-releasing hormone [GnRH]-induced luteinizing hormone [LH] pulsations during frequency sampling studies) of all of the genes associated with this condition.
[citation needed] During childhood, since the hypothalamic GnRH-pituitary-gonadal axis is quiescent, a diagnosis of GnRH insensitivity can generally be heralded only in the presence of nonreproductive phenotypes (e.g., the lack of sense of smell in some patients [anosmia] or skeletal abnormalities, such as cleft lip/cleft palate, hearing deficits, or syndactyly).
[citation needed] Some patients present with partial forms of GnRH insensitivity and undergo some degree of pubertal development that subsequently ceases.
For example, some males with GnRH insensitivity exhibit some testicular growth, while some females can have thelarche and menarche, but hypogonadotropic hypogonadism (HH) is demonstrable soon thereafter.
As many of the genes causing GnRH insensitivity have pleotropic physiologic functions, genetic testing can aid assessment of both reproductive and nonreproductive clinical features.
[citation needed] The choice of therapy for GnRH insensitivity depends upon the patient's age and desire to achieve one or more of the following goals:[citation needed] Puberty induction and sexual maturation Girls and women — Exogenous estrogens are used to start secondary sexual development in prepubertal girls and to build and sustain normal bone and muscle mass.
Initial therapy consist of unopposed estrogen alone to maximize breast growth, achieve appropriate skeletal maturation, and to induce uterine and endometrial proliferation.
[citation needed] Whichever form of testosterone replacement is chosen, providing psychological support is important because the patient will have a variety of new and often confusing symptoms, much like an adolescent undergoing puberty but more difficult because it will likely be at a later age.
[citation needed] The prognosis is generally good, with the outcome for fertility depending on the severity of the sex hormone deficiency and the age of initiation of treatment.
A population-based, epidemiological study from Finland showed a minimal prevalence estimate of the Kallman syndrome (KS) form of Gonadotropin-releasing hormone (GnRH) insensitivity to be 1:48,000 with a clear difference between males (1:30,000) and females (1:125,000).