What is Kallmann Syndrome & How is it Treated?|Causes, Signs, Symptoms, Prognosis of Kallmann Syndrome

Kallmann syndrome is a condition where the puberty stage is completely absent or delayed in some cases. In the life cycle of human beings, puberty is one of the most important stages as it is the stage of growth spurt in both boys and girls. In this article, we discuss about Kallmann syndrome in detail.

What is Kallmann Syndrome?

There would be many significant changes in the physical and mental growth in this period as a result of many physiological and hormonal changes. Growth of secondary sexual characters is seen in this syndrome. A boy becomes a man and a girl a woman in this stage. All these changes are due to changes in the hormones which are produced from their gonads. In males, testosterones are responsible for the changes in puberty whereas in females, estrogen and progesterone are produced.

In individuals if these hormones which bring about sexual development are lacking, they suffer from a condition known as hypogonadism. Kallmann syndrome is also known as hypogonadotropic hypogonadism. This syndrome is named after a geneticist Franz Josef Kallmann who published about Kallmann Syndrome in a paper.

Signs and Symptoms of Kallmann Syndrome

As the sex hormones in males and females differ, the presentation also differs accordingly. Some of the main signs and symptoms of Kallmann syndrome.

In males, hypogonadotropic hypogonadism is symptomized by.

  • Micropenis (size of penis is considerably reduced)
  • Cryptorchidism (undescended testes)
  • Lack of growth spurt
  • Underdeveloped secondary sexual characters like deepening of voice, facial and thoracic hairs, widening of chest, masculine behavior
  • Become infertile if not treated
  • Impaired sense of smell (hyposmia – reduced capacity of identifying smell or anosmia – inability to identify the smell).
  • In females, Kallmann syndrome shows the following features.
  • Delayed menstruation
  • Under developed breast
  • Lack of growth spurt
  • Become infertile if not treated
  • Impaired sense of smell (hyposmia or anosmia).

In general, there are some signs and symptoms of Kallmann syndrome shown irrespective of gender. Some of them are.

  • Loss or diminished sense of smell
  • Unilateral renal agenesis – one kidney is failed to develop
  • Cleft lip with or without cleft palate
  • Abnormalities of bones like osteoporosis
  • Eye defects with abnormal eye movements
  • Inability to hear properly
  • Improper development of teeth
  • In some cases, bimanual synkinesis is observed
  • Poor balancing and coordination.

Kallmann syndrome can be distinguished from other hypogonadotropic hypogonadism disorders with the presence or absence of sense of smell. In other forms of hypogonadism, sense of smell is not affected. In fact, the individuals suffering from Kallmann disorder do not know that they have impaired sense of smell until it is confirmed through testing by the professionals. In case of bimanual synkinesis, both the hands are not able to do the work independently. Movement of one hand would be mirrored by the other hand. In such cases, the individuals are unable to move both the hands separately. So it is difficult for them to involve in activities like playing musical instruments, typing, etc.

Causes for Kallmann Syndrome

One of the main causes of Kallmann syndrome is the lack of sexual hormones. In males and females, lack of testosterones and estrogen respectively cause this syndrome. Deficiency in production of Gonadotropin Releasing Hormone is main cause of this syndrome.

Kallmann syndrome is a genetic disorder where there might be mutations in one or more genes such as ANOS1, CHD7, FGF8, FGFR1, PROK2, and PROKR2. From researches, it is found that the gene responsible for migration of neurons which produces gonadotropin-releasing hormone is also involved in the migration of neurons from developing nose to frontal lobe of brain. Gonadotropin releasing hormone (GnRH) controls the production of hormones in males and females at puberty. So it is responsible for normal functioning of gonads. At the same time since the same genes are responsible for migration of neurons related to olfactory lobe, sense of smell is also impaired. From the researches, it is found that this is the main reason why the patients with Kallmann syndrome lack in secondary sexual characters and lost sense of smell.

How is Kallmann Syndrome Inherited?

Let us look at the way in which Kallmann syndrome is inherited. ANOS1 is situated on X- chromosome. Males have one copy of X-chromosome. The disease is passed on to the daughter if the father has mutated gene of ANOS1 since it is X-chromosome linked. Father cannot pass the disease to the son. In case of mothers who have 2 copies of X – chromosomes, if one copy of X – chromosome has mutated ANOS1 gene, the chance of passing to the daughter is 50%. This is because; ANOS1 is a X-lined recessive gene. Hence there may be crisscross inheritance.

An autosomal dominant inheritance pattern is the cause in some individuals if mutation occurs in other genes. In such cases, each cell has one copy of mutated gene.

In many cases, this syndrome exhibits autosomal recessive pattern of inheritance. Here, the disease is passed on to the next generation if both the copies of gene are mutated in each cell.

In some cases, the individuals do not have any family history and the new mutations can occur.

Diagnosis of Kallmann Syndrome

The diagnosis of Kallmann syndrome can be confirmed by conducting many tests, which include the following,

Clinical Examination for Kallmann Syndrome. This evaluation is done on different factors like height, pubic hair development in males and females, size of gonads, breast development at menarche, checking sense of smell, pigmentation of skin and hair, neurodevelopment. After conducting relevant examinations, the values are compared with the standard values for evaluation. This is an important part of the diagnosis of Kallmann syndrome.

Laboratory Tests to Diagnose Kallmann Syndrome. In laboratories, some tests are conducted for confirmation of this disease. FSH, LH, testosterone, estrogen and prolactin hormones are tested which is done early in the morning. GnRH level is confirmed to know the functional stage of hypothalamus and pituitary. Sperm is tested for confirmation of infertility. Bone density is checked to know about the lack or excess deposition of calcium.

Imaging Tests. Scanning of kidneys to confirm the presence of both the kidneys (to confirm whether the patient has renal agenesis), MRI of brain to get to know the abnormalities of brain if there is any, X-ray to find out the bone age, etc., are done in medical imaging.

Treatment of Kallmann Syndrome

The syndrome is observed in both males and females at puberty. There are several treatments to develop the secondary sexual characters. The treatment of Kallmann syndrome includes

  • A small surgery for micropenis condition or gonadotropin treatment is sometimes required for the males to correct undescended testes.
  • Sex hormone replacement is available for both males and females. There are different hormone replacements such as testosterone, estrogen and progesterone.
  • Medications to enhance the activity of FSH and LH which in turn increase the production of sex hormones.

Fertility is induced by GnRH pulsatile therapy. In males it is helpful to increase the production of sperm. In cases of undescended testes, other medications like intracytoplasmic sperm injection may be tried as there will be delay in production of sperms. In females, GnRH pulsatile therapy mainly addresses the induction of ovulation. Sometimes, medications may be required to trigger the maturation and release of eggs in females to facilitate natural conception.

As such there is no treatment for improving the sense of smell, mirror movements of hands and absence of one kidney.

For some cases, rehabilitation therapies, in addition to the main treatment of Kallmann syndrome can help and is best decided by the treating doctor.

Prognosis of Kallmann Syndrome

Timely treatment brings successful result in people suffering from Kallmann syndrome. Records tell us that there are a very few cases where the reversal of symptoms are reported that is 10% to 20%. Also, the reversal is found to be temporary.

Epidemiology of Kallmann Syndrome

Kallmann syndrome is most commonly found in males than in females. The disease is about 2.5 times more in males if there is a family history.


Kallmann syndrome is related to mutation in genes, particularly which is located on X-chromosome. This syndrome can be observed in both males and females at the age of puberty. The syndrome is detected by clinical examination of the features of boys and girls at puberty and diagnosis of Kallmann syndrome is made by confirmed laboratory tests. Treatment well in time helps people to avoid infertility, thus help reproduce in a natural process and lead a healthy life though sense of smell and mirror movements of hands cannot be treated at present.

Sheetal DeCaria, M.D.
Sheetal DeCaria, M.D.
Written, Edited or Reviewed By: Sheetal DeCaria, M.D. This article does not provide medical advice. See disclaimer
Last Modified On:March 28, 2019

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