This is an inherited condition that develops when the body does not produce sufficient gonadotrophin-releasing hormone (GnRH). This is essential for the stimulation of the testicles and the ovaries to produce sex hormones. As the result of this, this syndrome is characterized by the delayed or the absent puberty and impaired sense of smell. Kallman syndrome appears to affect more males than the females and the prevalence is estimated at 1 in 30,000 males and 1 in 120,000 females.
Causes
Around 20 genetic mutations are associated with this syndrome and some of the common genetic mutations identified include ANOS1, CHD7, FGF8, FGFR1, PROK2 or PROKR2. They are involved in the migration of nerve cells from the nose moving to the structure in front of the brain known as olfactory bulb which is important for the perception of smell. These genes are also involved in the migration of neurons from the nose to the front of the brain that produces the GnRH which are important for the function of the ovaries and the testes. The genetic mutation disrupts the migration process of the olfactory nerve cells to the olfactory bulb and the GnRH-producing nerve cells in the brain. As the result, the sense of smell is affected and the production of the sex hormones is prevented. When the ANOS1 genetic mutation is identified, the inheritance mode is the X-linked recessive pattern where the defective gene is located in one of the sex chromosomes and as the males only have one X chromosome, they are prone to have this condition. Autosomal dominant and autosomal recessive pattern of inheritance has also been identified depending on the particular gene involved.
Symptoms
The affected individuals have difficulty with the sense of smell which can be very poor or non-existent. The boys present small penis and delayed puberty. The secondary sexual characteristics are also absent such as body hair growth, genital enlargement, decreased pubic hair and facial hair growth. The girls have the delay in their breast growth and the absence of menstruation. These individuals often don’t have sexual interest and poor sexual function. If this condition is left untreated, these cases will be infertile. Additional features include cleft lip or palate, a problem with the development of one kidney, short fingers, abnormality with eye movement, bent spine (scoliosis) and deafness.
Diagnosis
The diagnosis of this condition is based on the identification of the problem with the sexual maturation that is established with the physical examination. The stimulation test with children is done to diagnose this syndrome. This involves an injection of GnRH and the levels of the sex hormones are assessed. If the level remains low, this condition is diagnosed. Among the adults, the blood test can determine the hormone levels which can confirm the syndrome.
Treatment
The hormone replacement is the treatment options to help the affected children reach puberty. This involves giving testosterone for the boys and estrogen and progesterone for the girls. This is usually a long-term treatment which is based on the type of hormone required for different aged children. There is no treatment to activate the sense of smell for these individuals.
References
https://rarediseases.org/rare-diseases/kallmann-syndrome/
http://www.rch.org.au/kidsinfo/fact_sheets/Kallmann_syndrome_an_overview/
https://ghr.nlm.nih.gov/condition/kallmann-syndrome#inheritance
