Kallmann syndrome

Kallmann syndrome is a genetic disorder that causes a condition known as hypogonadotropic hypogonadism (HH), in which very little sex hormones are produced. Kallmann syndrome is typically diagnosed at puberty due to a lack of sexual development, and affects fertility. Kallmann syndrome also causes an impaired sense of smell.

What is Kallmann syndrome?

Kallmann syndrome is a genetic disorder that causes hypogonadotropic hypogonadism (HH), a hormone deficiency caused by a problem in the pituitary or hypothalamus. This condition is characterized by a delayed or even absent puberty. Consequently, Kallmann syndrome is typically diagnosed at the time of puberty due to a lack of sexual development. Specifically, this disorder prevents the production of sexual hormones such as testosterone and estrogen, stunting secondary sexual development. 

Male patients with Kallmann syndrome do not develop secondary sex characteristics, including facial or body hair, or the deepening of their voice. Furthermore, those with Kallmann syndrome typically have an unusually small penis and suffer from undescended testes (also known as “cryptorchidism”). Similarly, Kallmann syndrome in females can have an impact on menstrual cycles, breast development, and growth spurts. In addition, this disorder tends to impair the sense of smell in both sexes. Kallmann syndrome is more commonly diagnosed in males than females. 

Kallmann syndrome and fertility

Those with Kallmann syndrome often require hormone replacement therapy (HRT) to conceive biological children. The lack of pubertal development leads to a reduction of sex hormone levels, inlcuding testosterone and estrogen, leading to infertility. Furthermore, Kallmann syndrome can lead to the absence of sexual interest, as well as poor sexual function, such as erectile dysfunction

Causes of Kallmann syndrome

Mutations in over 20 genes have been associated with Kallmann syndrome. The most common gene mutations are ANOS1, CHD7, FGF8, FGFR1, PROK2, or PROKR2. These genes have a direct impact in the development of the brain prior to birth. Kallmann syndrome disrupts the migration of olfactory nerve cells in the developing brain, which explains the impairment of the sense of smell. People with KS also do not have high enough levels of the reproductive hormones — including LH and FSH — typically produced in the pituitary.

Treatment of Kallmann syndrome

Kallmann syndrome is typically treated with hormone replacement therapy, with the main focus on inducing puberty. However, the dosage will ultimately depend on the specific individual and must be administered accordingly. Once puberty is triggered, the goal is to maintain normal hormone levels. This treatment can also be used to address infertility caused by Kallmann syndrome. 

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