Kallmann Syndrome (KS) – Symptoms, Causes & Treatment

By (gynecologist), (gynaecologist), (embryologist) and (invitra staff).
Last Update: 12/10/2019

Kallmann Syndrome (KS), also known as Maestre-Kallmann-Morsier Syndrome, is a genetic disease associated with hypogonadotropic hypogonadism, and smell disorders, including anosmia and hyposmia.

The disease can occur in both males and females, although it is more frequent in men. The prevalence of Kallmann Syndrome is 1 out of 8,000 males, and 1 out of 40,000 females.

Because KS affects the whole hypothalamic pituitary adrenal (HPA) axis and sex hormone production, it it considered to be a cause of infertility.

Definition & causes

The German psychiatrist Franz Josef Kallmann (1897-1965) described and characterized this genetic disorder as a hereditary condition under the name Kallmann Syndrome (KS).

KS has a genetic origin and, as such, based on the type of mutation, it can have an autosomal dominant, autosomal recessive, or linked to X-chromosome inheritance.

People with KS lack the surge of GnRH (gonadotropin-releasing hormone) due to a failure during embryonic development.

Particularly, it is due to an error in the migration of hypothalamic neurons in charge of GnRH synthesis from the olfactory epithelium to the hypothalamic area of the brain.

GnRH is one of the hormones in charge of the hypothalamic pituitary adrenal (HPA) axis. When the hypothalamus releases GnRH, the hypophysis is stimulated to produce the hormones FSH and LH.

Simultaneously, FSH and LH are responsible for the regulation of sexual development in males and females.


Due to hypogonadotropic hypogonadism (HH) caused by KS, hence the common abbreviation KS-HH, people affected by it have an incomplete development of the reproductive system, along with a lack of sexual development.

As a result, both men and women will have poorly-defined secondary sexual characteristics when they reach puberty, aside from infertility issues.

The following are the most important signs and symptoms of Kallmann Syndrome in both sexes:

In males

Based on age and the development phase the male finds himself in, it is possible to detect different alterations associated with KS.

For example, during childhood, having a micropenis and cryptorchidism can lead parents to suspect that their son may have this disorder.

After puberty, when the person reaches adulthood, men affected by KS will have a phenotype that is related to hypogonadism, along with a lack of testosterone:

  • Reduced bone density and muscle mass
  • Small testicular volume
  • Erectile dysfunction
  • Decreased libido
  • Oligospermia or azoospermia

Moreover, adult men affected by KS typically look like teenagers, since some characteristics of childhood continue in their adulthood.

In females

Common symptoms of KS in females are primary amenorrhea and an incomplete or absent development of the breasts during puberty.

Due to the lack of female sex hormones, such as estrogens, these women have anovulatory cycles (i.e. no egg is released). In other words, they have infertility problems.

Other symptoms

A symptom of KS that is common in both sexes is, as explained above, the partial or total absence of the sense of smell, due to an incomplete development of the olfactive bulbs.

Also, although less frequently, affected individuals may have the following alterations as well:

  • Renal disorders, like unilateral renal agenesis (URA)
  • Moderate mental retardation
  • Hearing loss
  • Involuntary hand and/or eyeball movements
  • Cleft palate
  • Cleft lip


To determine whether someone actually suffers from KS, different diagnostic methods may be used:

Hormone assessment
FSH and LH hormones are measured, along with sex hormones, as testosterone and estrogens.
Olfactory test
The sense of smell is evaluated qualitatively and quantitatively. The olfactory bulbs can be seen via MRI.
Clinical signs of hypogonadism
Lack of secondary sexual characteristics, including amenorrhea, erectile dysfunction, loss of sex drive, etc.
Genetic screening
To identify the exact mutation that causes the disease.


The treatment of Kallmann Syndrome aims to achieve pubertal feminization or virilization in patients.

To this end, a hormonal replacement therapy is essential to be able to develop and maintain the secondary sexual characteristics. As for males, some examples are: body hair growth, deeper voice, muscle and bone development... In the case of women, the goal is to promote breast growth, have normal menstrual periods, pubic hair, etc.

Broadly speaking, KS patients typically require lifelong treatment.

When a person that suffers from KS wants to have children, hormone treatment should be changed in order for fertility to be restored. What follows are some recommended treatments based on gender:

Males with KS
Repeated GnRH injections promote spermatogenesis. Thus, sperm are expected to be detectable within 3 months. Another option is to combine hCG injections with FSH, since it increases the concentration of intratesticular testosterone.
Females with KS
Hormone therapy is administered in order to stimulate the ovaries mildly. Then, timed intercourse is recommended.

Should pregnancy not take place with any of these treatment options, or in case there exist more serious infertility issues, the couple might have no alternative but to undergo intrauterine insemination (IUI) or in vitro fertilization (IVF) to become parents.

Also, considering the use of PGD/PGS (genetic testing of embryos) to prevent the transmission to offspring is highly recommended.

To perform a PGD, one should undergo IVF as the main treatment. If you are looking for a clinic to get started, we recommend that you generate your individual Fertility Report now. It is a useful, simple tool that, in just 3 steps, will give you a list of the clinics that have passed our rigorous selection process. You will receive an email in your inbox with a report that contains tips and recommendations to get started.

Finally, as regards the recovery of the sense of smell, unfortunately there exists no cure or treatment nowadays.

FAQs from users

Is Kallmann syndrome curable?

By Blanca Paraíso M.D., Ph.D., M.Sc. (gynecologist).

The cause of Kallman syndrome is genetic, with different genes involved. Therefore, there is no cure as such. Treatment consists of exogenously giving the body the hormones it needs for proper pubertal development. In women estrogens are administered and in men testosterone, in both cases they will be maintained indefinitely.

In addition, if there comes a time when the patient wishes to have children, the hypothalamic pituitary gonadal axis must be activated with medication. GnRH or FSH and LH can be administered to activate the ovaries and testicles.
Read more

What distinguishes Kallmann Syndrome from other genetic diseases?

By Zaira Salvador B.Sc., M.Sc. (embryologist).

Kallmann Syndrome (KS) is a type of hypogonadotropic hypogonadism that occurs at birth, since it has a genetic and hereditary origin. However, it is also possible that the mutations that cause this disorder arise de novo.

Individuals affected by KS have an inadequate development of secondary sexual characteristics when they reach puberty, resulting in infertility during adulthood.

On the other hand, KS alters the sense of smell, causing disorders like anosmia and hyposmia.

Can I be a mother if I have hypergonadotropic hypogonadism?

By José Carlos Mora Palma M.D. (gynaecologist).

The causes of hypergonadotropic hypogonadism are multiple and give rise to an alteration in ovarian function, conditioning fertility.

In general terms, we can state that the possibility of gestation will be determined by whether or not there is an ovarian follicular endowment and the integrity of the uterine factor. If both criteria are met, gestation would be possible through spontaneous gestation or Assisted Reproduction techniques (artificial insemination, in vitro fertilisation or gamete or embryo donation).

On the other hand, if there is no follicular endowment and uterine integrity is maintained, gestation through gamete or embryo donation would be possible.

Imagen: being-a-mother-with-hypogonadism-hypergonado-hypertropic-faq

It is important to underline that in cases where hypergonadotropic hypogonadism is associated with a genetic syndrome, Preimplantation Genetic Diagnosis is recommended in cases of in vitro fertilisation.

What genes cause Kallmann Syndrome?

By Zaira Salvador B.Sc., M.Sc. (embryologist).

There exist several genetic mutations of different types of inheritance that can cause someone to develop Kallmann Syndrome:

  • Sex-linked inheritance: KAL1 (Xp22.32)
  • Autosomal dominant inheritance: FGFR1 (8p12), FGF8 (10q25-q26), CHD7 (8q12.2), and SOX10 (22q13.1)
  • Autosomal recessive inheritance: PROKR2 (20p12.3), and PROK2 (3p21.1)

Depending on the mutation and gene affected, carriers of Kallmann Syndrome have no choice but to conceive using reproductive technologies in order to prevent the transmission of this genet to offspring.

Suggested for you

As explained earlier, Kallmann Syndrome is a genetic disease that can be inherited by offspring. To learn more about the different types of inheritance and their risk of transmission, continue reading here: What Genetic Diseases Can PGD Test for?

To get a much deeper insight on Kallmann Syndrome, it is crucial that one is familiar with the wide range of hormones that play a role in the organism of males and females. Recommended for you: Male & Female Sex Hormones – Definition & Functions.

We make a great effort to provide you with the highest quality information.

🙏 Please share this article if you liked it. 💜💜 You help us continue!


Freitas P, Carvalho S, Ribeiro F, Marnoto D, Martins F. Neuroradiology of Kallmann’s syndrome. Acta Med Port 2001;14:123-6.

Kallmann FJ, Schoenfeld WA, Barrera SE. The genetic aspects of primary eunuchoidism. Am J Ment Defic 1944;48:203-6.

Moorman JR, Crain B, Osborne D. Kallmann’s syndrome with associated cardiovascular and intracranial abnormalities. Am J Med 1984;77: 369-72.

Munez A, Dieguez E. A plea for proper recognition: The syndrome of Maestre de San Juan-Kallman. Am J Neuroradiol 1997;18:1395-6.

Seminara SB, Hayes FJ, Crowley WF Jr. Gonadotropin-releasing hormone deficiency in the human (idiopathic hypogonadotropic hypogonadism and Kallmann’s syndrome): pathophysiological and genetic considerations. Endocr Rev 1998;19:521–39

Stern Y, Egelhoff J, Shott SR. Imaging quiz. Absence of the olfactory bulb and tracts consistent with Kallmann syndrome. Arch Otolaryngol Head Neck Surg 1998;124:342-3.

Truwit CL, Barkovich AJ, Grumbach MM, Martini JJ. MR imaging of Kallmann Syndrome: A Genetic Disorder of neuronal migration affecting the Olfactory and Genital systems. Am J Neuroradiol 1993;14:827-38.

FAQs from users: 'Is Kallmann syndrome curable?', 'What distinguishes Kallmann Syndrome from other genetic diseases?', 'Can I be a mother if I have hypergonadotropic hypogonadism?' and 'What genes cause Kallmann Syndrome?'.

Read more

Authors and contributors

 Blanca Paraíso
Blanca Paraíso
M.D., Ph.D., M.Sc.
Bachelor's Degree in Medicine and Ph.D from the Complutense University of Madrid (UCM). Postgraduate Course in Statistics of Health Sciences. Doctor specialized in Obstetrics & Gynecology, and Assisted Procreation. More information about Blanca Paraíso
License: 454505579
 José Carlos Mora Palma
José Carlos Mora Palma
José Carlos Mora Palma studied Medicine at the University of Seville and has completed several expert courses, as well as several master's degrees. Currently, Dr. Mora Palma works as a gynaecologist at Next Fertility Sevilla. More information about José Carlos Mora Palma
Member number: 411811905
 Zaira Salvador
Zaira Salvador
B.Sc., M.Sc.
Bachelor's Degree in Biotechnology from the Technical University of Valencia (UPV). Biotechnology Degree from the National University of Ireland en Galway (NUIG) and embryologist specializing in Assisted Reproduction, with a Master's Degree in Biotechnology of Human Reproduction from the University of Valencia (UV) and the Valencian Infertility Institute (IVI) More information about Zaira Salvador
License: 3185-CV
Adapted into english by:
 Romina Packan
Romina Packan
inviTRA Staff
Editor and translator for the English and German edition of inviTRA. More information about Romina Packan

Find the latest news on assisted reproduction in our channels.