Kallman syndrome: symptoms, causes and treatment

Kallman syndrome is a genetic disorder that affects the sexual characteristics.

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 males than in females, in a ratio of 5:1.

In this article we will see what Kallman's syndrome consists ofThe main clinical manifestations and symptoms, how it is diagnosed and what is the indicated treatment.

What is Kallman syndrome?

The Kallman syndrome is a rare hereditary disease characterized by the combination of hypogonadotropic hypogonadism and anosmia or hyposmia. (absence or decrease of the 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.

The syndrome syndrome is named in honor of the psychiatrist Franz Kallmanwho in 1944 described this disease in detail in three families, postulating its hereditary nature.

People suffering from hypogonadotropic hypogonadism have insufficient or no sexual development, due to a deficiency of sex hormones and low levels of luteinizing hormone and follicle-stimulating hormone (hormones released by the hypogonadotropic (hormones released by the pituitary gland that regulate sexual reproduction), as well as infertility. Anosmia or hyposmia, on the other hand, is related to the absence or hypoplasia (incomplete development) of the olfactory bulb and its 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, about 5 times less than men.

It is a genetically heterogeneous condition and in 60% of cases it is sporadic, with no family history. Research has determined that there are three types of inheritance patterns 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 within families.

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

In women, amenorrhea, absence of breast development and dyspareunia may occur. amenorrhea, absence of mammary development and dyspareunia (painful coitus),

Moreover, patients with Kallmann syndrome may have other associated symptoms, which are also due to defects in embryonic genesis and are therefore related to the chain of fibroblast growth factors (substances responsible for functions such as the formation of Blood vessels or embryonic development).

Among the most common alterations associated with this syndrome include the following: synkinesias (involuntary and unconscious jerks that occur when performing voluntary movements), agenesis of the corpus callosum, visuospatial disorder, congenital palpebral ptosis, auditory disturbancesThe following are some of the less common disorders: hypodontia (defective development of one or more teeth), unilateral renal agenesis, cleft lip or palate, structural alterations in the feet or hands, obesity and other less frequent disorders.

Diagnosis

The vast majority of cases of Kallman syndrome are diagnosed in adolescence, due to the absence of secondary sexual characteristics, which translates, as far as males are concerned, into prepubertal testicles and absence of virilization; and in females, poor breast development and the presence of primary amenorrhea.

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

On the other hand, the pituitary gland is maintained under normal conditions, as is 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 by using specific olfactory tests for odor identification.

Neuroimaging techniquesIn the case of Kallman's syndrome, molecular techniques, such as magnetic resonance imaging, contribute to the diagnosis by detecting 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 performed to provide more clues for an accurate diagnosis.

For the diagnosis of Kallman syndrome there are also molecular techniques such as: fluorescent in situ hybridization, a chromosome marking technique by which chromosomes are hybridized with probes that emit fluorescence and allow visualization, distinction and study of chromosomes and their abnormalities; and comparative genomic hybridization, another cytogenetic technique that allows analysis of the quantity and structure of chromosomes compared with a reference chromosome.

Treatment

Treatment of patients with Kallman's syndrome has two goals: improve fertility and treat hypogonadism.. For the latter, it is necessary to stimulate the development of secondary sexual characteristics. This is achieved by hormone replacement therapy with testosterone, in the case of men; and with combined estrogens and progesterone, if women are affected.

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

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

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

Regarding anosmia or hyposmia, also characteristic of Kallman's syndrome, no specific treatment is yet available. available. Patients are usually advised to reduce the associated risks, such as: avoiding foods that may have expired, if there is no one else who can confirm whether a food is fresh; or 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 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:

• González, G. C., & Bonet, M. U. (2006). Etiopathogenesis of Kallmann's syndrome. Genotypic-phenotypic relationship. Endocrinology and Nutrition, 53(8), 519-524.
• Gutiérrez-Amavizca, B. E., Figuera, L. E., & Orozco-Castellanos, R. (2012). Kallmann syndrome. Genetic aspects and phenotypic variants. Revista Médica del Instituto Mexicano del Seguro Social, 50(2), 157-161.
• Rubio, L. R., de Paz Balboa, F., Sánchez, J. D., Herrera, P. A., & Fernández, J. T. (1981). Hypogonadotrophic hypogonadism and anosmia (Maestre San Juan-Kallman's syndrome)(author's transl). Anales españoles de pediatría, 15(4), 390-396.