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 is it diagnosed and what is the indicated treatment.
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 nasal passages 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 who suffer from hypogonadotropic hypogonadism have insufficient sexual development, or lack thereof, 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 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, 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
The clinical symptoms of Kallman syndrome show great variability between patients, even within families.
In men, hypogonadotropic hypogonadism secondary to gonadotropin-releasing hormone deficiency 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 may appear amenorrhea, absence of breast development and dyspareunia (painful intercourse),
On the other hand, patients who suffer from Kallmann syndrome may present other associated symptoms, which are also due to defects in embryonic genesis and, therefore, are related to the chain of growth factors of fibroblasts (substances responsible for functions such as the formation of blood vessels or embryonic development).
Among the most common alterations associated with this syndrome, the following should be highlighted: synkinesis (involuntary and unconscious jerks that occur when performing voluntary movements), agenesis of the corpus callosum, visuospatial disorder, congenital eyelid ptosis, hearing 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 common 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 men are concerned, into prepubertal testicles and 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 the administration of gonadotropin-releasing hormone (GnRH), but with a normal response when the hormones are injected repeatedly in pulses.
On the other hand, the pituitary gland is maintained in normal conditions, as well as the secretion of pituitary hormones. There is a decrease in steroid sex hormones and serum prolactin levels are at normal levels. Anosmia or hyposmia can be confirmed by clinical history or using specific olfactory tests for the identification of odors.
Neuroimaging techniques, like magnetic resonance imaging, contribute to making the diagnosis, since they allow the absence or hypoplasia of the olfactory bulbs to be detected; However, in up to 25% of patients this brain structure may be in perfect condition, and in these cases genetic studies must be performed that can provide more clues for an accurate diagnosis.
To diagnose Kallman syndrome, there are also molecular techniques such as: fluorescent in situ hybridization, a chromosome labeling technique by which chromosomes are hybridized with probes that emit fluorescence and allow the chromosomes and their anomalies to be visualized, distinguished and studied; and comparative genomic hybridization, another cytogenetic technique that allows analyzing the quantity and structure of chromosomes by comparing them with a reference one.
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 hormone replacement therapy with testosterone, in the case of men; and with combined estrogens and progesterone, if women are affected.
Testosterone therapy is now a safe treatment and it can be done through intramuscular injections, or using topical gels and liquids.
Hormone replacement treatment in women It usually consists of taking pills and oral drugs, with medical monitoring that guarantees a correct therapeutic process.
Regarding fertility treatment, human menopausal gonadotropin, or recombinant follicle-stimulating hormone (FSH), can be used to stimulate sperm production; and to stimulate folliculogenesis, the maturation process of the ovarian follicle, recombinant FSH or gonadotropin-releasing hormone can be administered in pulses.
In relation to 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 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 who suffers from this disease may suffer other types of alterations, such as deterioration in 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.
