Kallmann syndrome is a congenital disorder. It involves an underactivity of the gonads and loss of the sense of smell.
What is Kallmann syndrome?
Kallmann syndrome (KS) is also known as olfactogenital syndrome. In this disease, affected individuals suffer from a diminished or completely absent sense of smell. Furthermore, there is an underfunction of the gonads (hypogonadism) such as the male testes or female ovaries. Kallmann syndrome is congenital and is a rare disease. Men are affected by it significantly more often than women. Thus, the frequency in men is 1:10,000, while in the female sex it is 1:50,000. The disease was named after the German psychiatrist Franz Josef Kallmann (1897-1965). Kallmann syndrome was first mentioned in 1856 by the Spanish physician Aureliano Maestre de San Juan. Therefore, the disease also bears the name Sindrome de Maestre-Kallman-Morsier in Spanish-speaking regions.
Causes
Kallmann syndrome is triggered by genetic defects, or more precisely, by mutations that are evident in a protein. This protein is exceedingly important for the development of the olfactory bulb (bulbus olfactorius) as well as various nuclear areas of the hypothalamus. Cells producing gonadoliberin (GnRH) enter the forebrain from the nasal placode during embryonic development. However, the exact pathway remains unclear to date. The cell bodies are located in the hypothalamus in the regio supraoptica, while the extensions extend into the eminentia mediana. From there, they release releasing hormones toward the portal circulation. The hormones ensure the release of the gonadotropins LH and FSH. In this way, the female menstrual cycle and spermatogenesis and testosterone production in the male are controlled. In the case of Kallmann syndrome, however, aplasia (non-formation) of the olfactory bulb occurs for genetic reasons. Up to now, two mutations could be described which are considered to be responsible for the development of Kallmann syndrome. These are the KAL mutation on the X chromosome and the FGFR1 gene on chromosome 8. These mutations cause a developmental disorder of the central nervous system (CNS). There is a disturbance in the immigration of nerve cells to the place that is physiologically determined for them. The disorder is manifested by abnormalities of the hypothalamus. Due to the impairment of the hypothalamus, the hormone GnRH can only be insufficiently released, which has a negative effect on the release of FSH and LH as gonadotropins. The maldevelopment of the olfactory bulb in turn results in the loss of the sense of smell.
Symptoms, complaints, and signs
The symptoms that occur in Kallmann syndrome can vary widely. The leading symptom is an impaired sense of smell, known as hyposmia, or complete loss of the sense of smell, known as anosmia. The second defining symptom is the delay or total absence of puberty. In this case, the affected individuals do not develop secondary sexual characteristics. In the male sex, for example, the voice does not break. Beard growth and body hair are also affected. In the female sex, menstruation does not occur. In some cases, a craniofacial malformation also occurs. In this case, disproportions appear on the face and head. If Kallmann syndrome is X-linked, which occurs in about one third of all patients, a kidney is often missing. If, on the other hand, there is a mutation of the FGFR1 gene, cleft lip and palate malformation is also possible.
Diagnosis and course of the disease
Diagnosing Kallmann syndrome is often difficult. Particularly in women, symptoms are often inconspicuous in nature, sometimes causing the physician to overlook them during an examination. In addition, problems with odor development are usually not even noticed by patients because they are not familiar with other odors. As a result, Kallmann syndrome is not detected in some patients until they are older. An important diagnostic option is to check the level of testosterone or estrogen in the body. Gonadotropin levels become apparent through a prepubertal pattern. GnRH stimulation results in increased release of gonadotropins.The disorder of the sense of smell can be detected by olfactory testing. Abnormalities in the central nervous system can be detected by imaging methods such as magnetic resonance imaging (MRI). Both adolescent and adult males suffering from Kallmann syndrome require replacement therapy with testosterone throughout their lives. If appropriate treatment is given, normalization of puberty and sexual life is possible.
Complications
Kallmann syndrome results in most cases in an impaired sense of smell. This can also be completely lost as the disease progresses. As a result, patients experience significant difficulties in everyday life, and the quality of life is significantly reduced and limited by Kallmann syndrome. Furthermore, in addition to the limitations of the sense of smell, there is usually a complete absence of puberty. This absence has a very negative effect on the development of the child. Thus, for example, menstruation does not occur, nor does sexual development. Not infrequently, the patients also suffer from malformations in the head region. Furthermore, a kidney may also be missing. Due to a cleft palate, the patient’s aesthetics may also be impaired, resulting in significant inferiority complexes or greatly reduced self-esteem. However, the symptoms of Kallmann syndrome do not have to appear immediately after birth. In many cases, patients do not suffer from the symptoms of this disease until adulthood. Treatment of Kallmann syndrome can be carried out with the help of medications and hormones. No complications occur in this process. However, psychological treatment is usually also necessary to prevent complications in adulthood.
When should you go to the doctor?
If symptoms such as an impaired sense of smell or a failure to reach puberty are noticed, Kallmann syndrome may be underlying. A doctor should be consulted if the symptoms persist longer than usual or possibly even become permanent. If further symptoms occur, the family doctor must be consulted immediately. Girls and women who are not menstruating should talk to their gynecologist. Men who suffer from malformations in the genital area are best advised to consult a urologist. Kallmann syndrome can manifest itself through a wide variety of symptoms, which is why a doctor should be consulted at the first sign of the disease. Persons suffering from a hereditary disease should inform the responsible physician. With children, it is best to go to the pediatrician. In many cases, Kallmann syndrome is diagnosed and treated immediately after birth. Suitable contacts are speech therapists, orthopedists, gynecologists, urologists and specialists in hereditary diseases. In case of serious complications, the child should be taken to a clinic immediately.
Treatment and therapy
Therapy for Kallmann syndrome consists primarily of the administration of hormones such as testosterone or progesterone/estrogen. While the man receives testosterone, the woman is administered estrogen and progesterone, respectively. The supply of hormones can take place through the administration of gels, injections or special patches. Substitution treatment allows normal puberty to occur, enabling patients to lead relatively normal lives. It may even be possible to father children. If the patient has the desire to have children, replacement therapy with gonadotropins takes place. In most affected patients, sperm formation or oogenesis (formation of oocytes) can take place in this way. Especially in men, however, there is a limitation of fertility. It is also important to counteract bone loss (osteoporosis), because Kallmann syndrome also results in a reduction in bone density. The absence of the sense of smell, on the other hand, cannot be treated. Psychotherapy and human genetic counseling are also considered important therapeutic factors. It is also essential to treat the presence of anemia, which is often present in this disease.
Outlook and prognosis
If hormone therapy is initiated in a timely manner in affected individuals, normal pubertal development occurs. Males are assured, through lifelong administration of testosterone, of a normal sex life in adulthood.After adequate and timely hormone administration of estrogen and progesterone, there are no sexual functional limitations even in women. The hormones are usually injected via gels or patches. Hormone treatment at puberty results in feminization or masculinization in all patients. Psychological consequences can sometimes result from these hormone therapies, such as listlessness, mood swings or a change in libido. Therefore, under certain circumstances, psychological support for patients should be considered in addition to hormone therapy. If there is an existing desire to have children, the hormone administration of gonadotropin or gonadoliberin can stimulate the maturation of sperm cells or oocytes. On average, it can take between 18 and 24 months for sperm production to be fully restored. In about 80% of these cases, normal fertility is achieved. One empirical study reported five patients with Kallmann syndrome who experienced spontaneous recovery of gonadal function after several years of hormone replacement therapy.
Prevention
Because Kallmann syndrome is congenital and caused by a genetic defect, it cannot be effectively prevented.
Follow-up
Because Kallmann syndrome is hereditary and therefore a congenital disease, it cannot be completely cured or treated. In this regard, a physician should be contacted at the first symptoms and signs of the syndrome to prevent further complications or further worsening of symptoms. Early detection of the symptoms can lead to a positive course of the disease, although in most cases the measures and the possibilities of follow-up care are severely limited. The treatment of Kallmann syndrome is usually carried out by taking various medications. Affected persons should pay attention to a correct dosage and also to a regular intake of the medication in order to alleviate the symptoms permanently. Especially in the case of children, parents must ensure that the medication is taken regularly. Not all of the symptoms of Kallmann syndrome can be completely alleviated, so that many patients are dependent on the help and support of their own family in their daily lives. In most cases, the life expectancy of those affected is not reduced by this disease. Further measures of aftercare are not available to patients with Kallmann syndrome.
Here’s what you can do yourself
Individuals who have Kallmann syndrome usually have diverse symptoms and therefore require comprehensive medical treatment. Since the individual symptoms often persist for a lifetime and this can place a considerable burden on the psychological state of those affected, therapeutic counseling is also usually indicated. In discussions with a therapist, the affected person learns how to deal with the disease and the problems it entails. In most cases, psychological counseling can also establish contact with other sufferers. This makes it easier to deal with Kallmann syndrome and offers the sufferer the opportunity to learn new strategies and tips for coping with everyday problems. In addition to these therapeutic measures, the sufferer can also support the treatment of the symptoms. The doctor will first recommend that the sufferer change his or her eating habits. A balanced diet can support hormone treatment. Regular exercise, sufficient sleep and the avoidance of stress contribute to this treatment. Accompanying medical monitoring is always indicated, as this is the only way to avoid complications. Should unusual symptoms develop or severe psychological problems occur, a visit to the doctor in charge is indicated.
