Kallmann syndrome is a congenital endocrine disorder that adversely affects the development of sexual organs in both males and females. Get detailed information about the condition, including its causes, symptoms, diagnosis, and treatment methods.
Kallmann syndrome Definition
This hormonal condition is characterized by delayed, incomplete or absent puberty. It is simply abbreviated as KS.
Kallmann syndrome Synonyms
The disorder is also known by various other names, such as:
- Anosmic hypogonadism
- Anosmic idiopathic hypogonadotropic hypogonadism
- Hypogonadotropic hypogonadism-anosmia syndrome
Kallmann syndrome Incidence
KS is 5 times more common in males than females. It affects 1 in 10,000 male births and 1 in 70,000 female births. It is a very rare condition that often goes underreported. Hence, a more accurate idea of the epidemiology may be difficult to establish.
Kallmann syndrome Symptoms
A simple constitutional delay of puberty could often be confused with KS, owing to the absence of reproductive features. The condition normally has the following clinical manifestations:
- Presence of small penis in males
- Failure of testicular development in males called Cryptorchidism
- Decreased libido and erectile dysfunction in males
- Absence of a menstrual period in females
- Incomplete development of secondary sexual characteristics in both genders
- Total absence of sense of smell (known as Anosmia)
- Hyposmia, or partial impairment of sense of smell
- Shortness of breath
- Bluish discoloration of the skin called cyanosis
- Loss of muscle tone
- Sensorineural hearing loss
- Impairment in motor or sensory function of the lower extremities
- Color blindness
- Decreased vaginal lubrication in females
- Craniofacial anomalies
- Abnormal ocular movements
- Dental defects
- Bimanual synkinesis
- Excessive bone growth
- Congenital absence or severe malformation of one or both kidneys
Kallmann syndrome Causes
There is a genetic defect underlying KS that causes a miscommunication between the hypothalamus and the anterior pituitary gland of the brain. Hypothalamus is a small portion of the brain, which normally secretes chemicals responsible for stimulating the master gland of the endocrine system called pituitary to release hormones that help in controlling functions like:
- Sexual development in both males and females
- Breast milk production
- Control of reabsorption of water by the kidneys
- Energy production
KS is a type of Hypogonadotropic Hypogonadism (HH) – a condition manifested by reduced functional activity of the testes and ovaries in males and females, respectively. HH normally exhibits these symptoms due to lack of secretion of gonadotropins, including follicle-stimulating hormone (FSH) and luteinizing hormone (LH) by the endocrine cells in the anterior pituitary gland. In both sexes, FSH regulates the development, growth, pubertal maturation, and reproductive processes of the body. In females, LH regulates the menstrual cycle and the process of ovulation whereas in males it stimulates the production of testosterone, which plays an essential role in sperm production. Genetic abnormalities impair the function of hypothalamus, causing decreased production of gonadotrophin releasing hormone GnRH responsible for the release of FSH and LH from the anterior pituitary. The end result is a failure of puberty and absence of secondary sexual characteristics.
Kallmann syndrome Pathophysiology
KS is caused by genetic mutations in AL1, FGFR1, PROKR2, and PROK2. These genes have a crucial role in the migration of olfactory and GnRH neurons in the fetal brain. Anomalies in the genes disrupt an individual’s sense of smell and interfere with the normal sexual development. The additional features of KS have been ascribed to the impact of various other genetic and environmental factors by several medical scientists. KS follows an X-linked recessive pattern of inheritance and can be passed from one generation to another. The KAL1 gene is located on the X chromosome, one of the two sex chromosomes present in each cell. As males carry a single X chromosome, one altered copy of the gene in each cell is sufficient to cause the disorder. However, mutation in the two copies of KAL1 gene is a prerequisite for causing KS in females, owing to the presence of two X chromosomes in them. Thus, males are more likely to develop the X-linked recessive disorder than females.
Kallmann syndrome Diagnosis
During a physical examination, clinicians can easily suspect the possibility of KS as signs like delayed puberty and impaired sense are symptomatic of this disorder. The family medical history is crucial to track the ailment as it may provide some information about the genetic makeup of the affected individuals. Some medical tests and exams for the diagnosis of KS include:
In KS-affected patients, a simple hematology test reveals a problem in the hypothalamus or the pituitary gland by showing the following features:
- Low levels of LH and FSH in males as well as in females
- Low serum testosterone in males
- Reduced levels of serum estrogen in females
- Decreased pituitary hormones in both genders
The highly-specialized technique can identify mutations in the KAL 1 gene and the other genes involved in this disorder.
A bone age study can be conducted using the X-ray technique to evaluate how an individual’s bones are maturing. A delayed growth or puberty is obvious when the test reveals a bone age lesser than the chronological or actual age of the patients.
Magnetic resonance imaging
Damaged olfactory neurons in the nose and deformity in the pituitary gland or hypothalamus can be confirmed with the help of MRI findings.
Commercially available testing kits, containing a variety of odorous chemicals are placed beneath the nostrils of the patients. These various sources of smell are then made to be identified. The inability of the patients to perceive the odors signifies some kind of malformation in the olfactory system.
Kallmann syndrome Treatment
The condition can be treated through therapeutic procedures like:
Hormone replacement therapy
The estrogen or combination estrogen /progesterone treatment is performed to raise the levels of the sex hormones in females and can be given in pill, patch, or gel form. Estrogen signals the start of a menstrual cycle. It is also responsible for causing development of the sex organs, including breast tissue. Progesterone regulates the estrogen level, and plays an important role in fertility by building up the endometrial lining and shedding it during menstruation when no pregnancy occurs. Testosterone replacement therapy can be prescribed as an intramuscular injection or in the form of capsules, patches or gels on the skin. Testosterone is needed to form and maintain the male sex organs as well as promote secondary male sex characteristics. It even facilitation the muscle growth as well as bone development and maintenance.
Health specialists can advice the patients to go for in vitro fertilization (IVF) or intake of fertility drugs like clomiphene, gonadotropins or bromocriptine to stimulate the production, and release of eggs and sperms. Administration of human chorionic gonadotrophin (hCG) can evoke testosterone production in males and ovulation induction in females.
Additional medical therapies are also used to treat the other symptoms, including osteoporosis.
If you are worried about delayed puberty, and have a family history of Kallmann syndrome, get quickly in touch with a healthcare provider. Early detection and quick treatment can restore normal pubertal development and fertility.