Kallman syndrome: symptoms, causes and treatment

Kallman syndrome is a rare disease that causes fertility problems and affects both sex hormone production and 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 is the Kallman syndrome, What are its main symptoms and clinical manifestations, how is it diagnosed and what treatment is indicated.

    What is Kallman Syndrome?

    Kallman syndrome is a rare inherited disorder characterized by the combination of hypogonadotropic hypogonadism and anosmia or hypoosmia (Absence or reduction of smell), due to a deficiency in the secretion of gonadotropin releasing hormones secondary to a defect in the migration of neurons which release these same substances from the nostrils to the hypothalamus.

    the syndrome it is named in honor of the psychiatrist Franz Kallman, Who in 1944 described in detail this disease in three families, postulating the hereditary nature of the same.

    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), as well as infertility. Anosmia or hypoosmia, on the other hand, is related to the absence or hypoplasia (incomplete development) of the olfactory bulb and its treatments.

    Kallman syndrome can be sporadic or familial, and although it can affect both men and women, women tend to have 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 they exist three types of inheritance patterns: X-linked, autosomal dominant and autosomal recessive.


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

    In humans, hypogonadotropic hypogonadism secondary to a deficiency in gonadotropin-releasing hormone can manifest as: 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.

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

    On the other hand, patients with Kallmann syndrome may have other associated symptoms, which are also due to abnormalities in embryonic genesis and are therefore linked to the chain of fibroblast growth factors (substances responsible for such functions. than blood vessel formation or embryonic development).

    Among the most common disorders associated with this syndrome are: synkinesia (involuntary and unconscious shocks occurring when performing voluntary movements) corpus callosum agenesis, visuospatial disorder, congenital eyelid ptosis, hearing impairment, Hypodontia (defective development of one or more teeth), unilateral renal agenesis, labial or palatal bile, structural changes in the feet or hands, obesity and other less common disorders.


      The vast majority of cases of Kallman syndrome are diagnosed in adolescence, due to the absence of secondary sexual characteristics, which results, for men, in prepubertal testes and a lack of virilization; and in women, poor breast development and the presence of primary amenorrhea.

      When diagnosed with Kallman syndrome, they can be found low or normal serum levels of luteinizing and follicle stimulating hormone, With a poor initial response to administration of gonadotropin releasing hormone (GnRH), but with a normal response when hormones are repeatedly injected into legumes.

      On the other hand, the pituitary gland is maintained under normal conditions, as is the secretion of pituitary hormones. There is a decrease in steroid sex hormones and serum prolactin levels are at normal levels. Anosmia or hypoosmia can be confirmed by a medical history or by using specific scent tests for odor identification.

      Neuroimaging techniques, Such as magnetic resonance imaging, help in diagnosing because they detect 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 must be done in order to be able to throw 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 they hybridize with fluorescent emitting probes and make it possible to visualize, distinguish and study chromosomes and its anomalies; and comparative genomic hybridization, another cytogenetic technique that allows the number and structure of chromosomes to be analyzed by comparing them to a reference chromosome.


      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 estrogen and progesterone, if women are affected.

      Testosterone therapy is safe treatment today and can be achieved by intramuscular injections, or by using topical gels and fluids.

      Hormone replacement therapy in women it usually consists of taking oral pills and medications, with medical supervision to ensure an appropriate therapeutic process.

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

      Regarding anosmia or hypoosmia, also characteristic of Kallman’s syndrome, there is still no specific treatment. available. Patients are often advised to reduce the associated risks, such as: avoiding foods that may have expired if no one else 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 suffers from other types of disorders, 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 to prevent the onset of osteoporosis.

      Bibliographical references:

      • González, GC and Bonet, MU (2006). Etiopathogenesis of Kallmann syndrome. Genotypic-phenotypic relationship. Endocrinology and Nutrition, 53 (8), 519-524.
      • Gutiérrez-Amavizca, BE, Figuera, LI and Orozco-Castellanos, R. (2012). Kallmann syndrome. Genetic aspects and phenotypic variants. Medical Journal of the Mexican Social Security Institute, 50 (2), 157-161.
      • Rubio, LR, by Pau Balboa, F., Sánchez, JD, Herrera, PA, and Fernández, JT (1981). Hypogonadotrophic hypogonadism and anosmia (Maestre Sant Joan-Kallman syndrome) (author’s translation). Spanish Annals of Pediatrics, 15 (4), 390-396.

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