Kallman syndrome: symptoms, causes and treatment

Kallman syndrome is a rare disease that causes fertility problems and affects both the production of sex hormones and the sense of smell, causing hypogonadism and anosmia, respectively. This disorder occurs more in men than in women, in a ratio of 5:1.

In this article We will see what Kallman syndrome consists of, what are its main manifestations and clinical symptoms, how it is diagnosed and what is the indicated treatment.

• Related article: "The 9 main sexual and psychosexual disorders"

What is Kallman syndrome?

Kallman syndrome is a rare inherited disease characterized by the combination of hypogonadotropic hypogonadism and anosmia or hyposmia (absence or decreased sense of smell), due to a deficiency in the secretion of gonadotropin-releasing hormones secondary to a defect in the migration of neurons that release these same substances from the nostrils to the hypothalamus.

Syndrome It is named after the psychiatrist Franz Kallman, who in 1944 described this disease in detail in three families, postulating its hereditary nature.

People with hypogonadotropic hypogonadism have insufficient or no sexual development, due to a deficiency of sex hormones and low levels of luteinizing and follicle-stimulating hormone (hormones released by the pituitary gland that regulate sexual reproduction), and also infertility. Anosmia or hyposmia, for its part, is related to the absence or hypoplasia (incomplete development) of the olfactory bulb and their tracts.

Kallman syndrome can be sporadic or familial, and although it can affect both men and women, the latter tend to suffer from it less frequently, around 5 times less than men.

It is a genetically heterogeneous condition and in 60% of cases it is sporadic, with no family history. The investigations carried out have determined that there are three types of inheritance patterns: X-linked, autosomal dominant, and autosomal recessive.

Symptoms

The clinical symptoms of Kallman syndrome show great variability between patients, even at the intrafamilial level.

In men, hypogonadotropic hypogonadism secondary to deficiency of hormone-releasing hormones gonadotropins can manifest with: micropenis, cryptorchidism (incomplete descent of one or both testicles into the scrotum), absence or incomplete development of secondary sexual characteristics, decreased libido, infertility and erectile dysfunction.

In women, it can appear amenorrhea, lack of breast development, and dyspareunia (painful intercourse),

On the other hand, patients suffering from Kallmann syndrome may present other associated symptoms, which are also due to defects in embryonic genesis and, therefore, Therefore, they are related to the chain of fibroblast growth factors (substances responsible for functions such as the formation of blood vessels or the development embryonic).

Among the most common alterations associated with this syndrome, the following should be highlighted: synkinesias (involuntary and unconscious jerks that occur when making movements volunteers), corpus callosum agenesis, visuospatial disorder, congenital ptosis, hearing impairment, hypodontia (defective development of one or several teeth), unilateral renal agenesis, lip or cleft palate, structural alterations in feet or hands, obesity and other less frequent.

• You may be interested in: "Types of hormones and their functions in the human body"

Diagnosis

The vast majority of cases of Kallman syndrome are diagnosed in adolescence, due to the absence of characters secondary sexual intercourse, which translates, as far as men are concerned, into prepubescent testicles and the absence of virilization; and in women, poor breast development and the presence of primary amenorrhea.

When diagnosing Kallman syndrome, one can find low or normal serum levels of luteinizing and follicle-stimulating hormone, with a poor initial response to gonadotropin-releasing hormone (GnRH) administration, but a normal response when the hormones are injected repeatedly in pulses.

On the other hand, the pituitary remains in normal conditions, as well as the secretion of pituitary hormones. There is a decrease in sex steroid hormones and serum prolactin levels are at normal levels. Anosmia or hyposmia can be confirmed by clinical history or using specific olfactory tests for odor identification.

neuroimaging techniques, such as magnetic resonance, help to make the diagnosis, since they allow the detection of the absence or hypoplasia of the olfactory bulbs; however, in up to 25% of patients this brain structure may be in perfect condition, and in these cases, genetic studies should be carried out that can shed more clues for a diagnosis accurate.

To diagnose Kallman syndrome, there are also molecular techniques such as: fluorescent in situ hybridization, a technique for labeling chromosomes through which they are hybridized with probes that emit fluorescence and allow to visualize, distinguish and study the chromosomes and their anomalies; and comparative genomic hybridization, another cytogenetic technique that allows the quantity and structure of chromosomes to be analyzed by comparing them with a reference chromosome.

Treatment

The treatment of patients with Kallman syndrome has two objectives: improve fertility and treat hypogonadism. For the latter, it is necessary to stimulate the development of secondary sexual characteristics. This is achieved through testosterone hormone replacement therapy, in the case of men; and with combined estrogen and progesterone, if women are affected.

Testosterone therapy is nowadays a safe treatment and it can be done by intramuscular injections, or using topical gels and liquids.

Hormone replacement therapy in women It usually consists of taking pills and oral drugs, with medical follow-up to guarantee a correct therapeutic process.

With regard to fertility treatment, to stimulate the production of spermatozoa, can use human menopausal gonadotropin, or also follicle-stimulating hormone (FSH) recombinant; and to stimulate folliculogenesis, the maturation process of the ovarian follicle, recombinant FSH or pulsed gonadotropin-releasing hormone can be administered.

Regarding anosmia or hyposmia, also characteristic of Kallman syndrome, there is still no specific treatment available. Patients are often advised to reduce associated risks, such as: avoiding foods that may have expired, if there is no one else who can confirm if a food is cool; o not cooking or heating with natural gas at home, as they may have difficulty detecting possible leaks.

Finally, it should be noted that it is possible that the person suffering from this disease may suffer other types of alterations, such as the deterioration of bone health, for example. It is important to perform a bone mineral density test to measure the amount of calcium and other minerals and prevent the onset of osteoporosis.

Bibliographic references:

• Gonzalez, G. C., & Bonet, M. OR. (2006). Etiopathogenesis of Kallmann syndrome. Genotypic-phenotypic relationship. Endocrinology and Nutrition, 53(8), 519-524.
• Gutierrez-Amavizca, B. E., Figuera, L. E., & Orozco-Castellanos, R. (2012). Kallman's syndrome. Genetic aspects and phenotypic variants. Medical Journal of the Mexican Social Security Institute, 50(2), 157-161.
• Rubio, L. R., de Paz Balboa, F., Sánchez, J. D., Herrera, P. A., & Fernandez, J. T. (1981). Hypogonadotrophic hypogonadism and anosmia (Maestre San Juan-Kallman's syndrome)(author's transl). Spanish Annals of Pediatrics, 15(4), 390-396.