Kallmann’s syndrome causes loss of sense of smell, hindering puberty – VnExpress

Kallmann syndrome is a genetic disorder that interferes with the function of the hypothalamus – pituitary gland, causing delayed or absent puberty, impaired olfactory function.

Doctor CKI Phan Thi Thuy Dung (Department of Endocrinology – Diabetes, Tam Anh General Hospital in Ho Chi Minh City) said that Kallmann’s syndrome is a form of congenital hypogonadism caused by a lack of certain hormones produced by the body. direction of sexual development. Normally, the hypothalamus – pituitary gland on the brain secretes gonadotropic hormones that activate puberty and reproductive functions. The disease is present at birth, however, it is often diagnosed late at 14-16 years old when parents notice that the child does not have the characteristics of puberty.

There are many causes that lead to the hypothalamus – pituitary gland to reduce the secretion of gonadotropic hormones, affecting the process of puberty. According to Dr. Dung, Kallmann syndrome accounts for about half of all causes of hypogonadism due to hypothalamic-pituitary dysfunction. Impaired olfactory function (inability to perceive odors) is the main symptom that helps early recognition and differentiation of Kallmann syndrome.

Other symptoms include: cleft lip, cleft palate, single kidney, hearing loss, abnormal eye movement, undescended testicle, finger bone abnormalities, hand syncope (tendency to mimic) movement of the other hand during movement makes it difficult to perform tasks that require separate hand movements, such as playing an instrument).

Dr. Dung added, Kallmann syndrome is a rare disease, occurring more in men than in women, with an incidence of 1 in 30,000 men and 1 in 120,000 women. Due to the genetic nature, this syndrome can be present from birth. Male patients often have an abnormally small penis and undescended testicles. During puberty, most people do not develop sexual characteristics such as: no beard, high-pitched voice (in boys), no menstrual periods, no breast development (in girls), no or less pubic hair, armpit hair…. If not treated soon, the patient will have infertility and psychological abnormalities, accompanied by metabolic disorders due to the decline in sex hormones.

Three inheritance patterns of Kallmann syndrome

Kallmann syndrome is inherited in three ways: X-linked inheritance, dominant inheritance and autosomal recessive inheritance.

X-linked inheritance: Men only need to receive an X chromosome carrying the mutated gene from their mother to be able to manifest the disease. For females (who have two X chromosomes), two mutated genes are needed. This type of inheritance also means that the father cannot pass the disease on to his son (since a son only receives a Y chromosome from his father). An example of Kallmann syndrome inherited in this way is the ANOS1 gene mutation.

Autosomal dominant inheritance: Only one of the parents carrying the mutated gene can pass it on to their children and cause the disease. A child only needs to carry a mutated gene to manifest the disease. Kallmann syndrome caused by mutations in genes such as PROKR2, PROK2, CHD7, FGF8 will have an autosomal dominant inheritance pattern.

Autosomal recessive inheritance: Both parents (often asymptomatic) can give birth to a child with Kallmann syndrome. In this case, the child must carry two disease-causing genes from the father and mother. The mutated genes in this case are PROKR and PROK2.

In people with Kallmann syndrome, genetic mutations change the movement or function of certain nerve cells in the brain, Dr. Dung explains. Before a baby is born, olfactory neurons (which are responsible for smell) and neurons that produce gonadotropin-releasing hormone (GnRH) are formed as the nose is developing. GnRH is a hormone in the hypothalamus that stimulates the pituitary gland to produce gonadotropins. Gonadotropin is a gonadotropin hormone in the pituitary gland, which acts on the sex organs such as the testes in men and the ovaries in women to secrete sex hormones…

Normally, when the fetus matures, nerve cells begin to move from the nose to the brain, to the hypothalamus (which is responsible for secreting the hormone GnRH, which regulates body temperature and breathing). However, due to certain genetic mutations, these neurons do not migrate properly during development in patients with Kallmann syndrome. As a result, after birth, people with Kallmann syndrome show a decline in olfactory function, difficulty perceiving scents. This also means that the brain does not release GnRH at normal levels.

When GnRH from the hypothalamus is depleted, the pituitary gland does not adequately secrete gonadotropic hormones such as FSH and LH. FSH is a hormone that stimulates follicle growth and spermatogenesis. LH is a hormone that releases eggs and stimulates the ovaries and testes to produce sex hormones such as estrogen and testosterone.

In the normal person, these hormones promote the gonads to produce testosterone and estrogen, which, in turn, promote the development of secondary sexual characteristics (such as breast growth, pubic hair growth, facial hair). People with Kallman syndrome may need hormone replacement therapy to promote the release of these hormones.

Diagnosis and treatment

The health abnormalities caused by this syndrome are usually present at birth but can be diagnosed later (puberty 14-16 years). The doctor diagnoses the disease based on a physical exam, performing endocrine tests, imaging, and genetic testing.

The doctor does a physical exam and tests to diagnose Kallmann syndrome. Image: Shutterstock

According to Dr. Dung, the main goal of treatment for Kallmann’s syndrome is to stimulate puberty and reestablish fertility. Hormone replacement therapy may begin with replacement of sex hormones such as testosterone for men; estrogen and progesterone for women. Testosterone and estrogen or progesterone replacement therapy by itself will not restore fertility. The goal of this therapy is to stimulate puberty and the development of secondary sex characteristics. Hormone therapy is also important for maintaining bone density, which can be impaired by a lack of sex hormones.

However, injectable therapy with hormones such as FSH or LH, as well as synthetic forms of GnRH, can help restore fertility as well as stimulate the ovaries and testes to synthesize sex hormones.

Dr. Dung cites several studies that show that 10-20% of people with congenital hypogonadism recover on their own to produce these hormones. This recovery may not last long, though. As adults, people with Kallmann syndrome also face the possibility of having a baby if left untreated. Hormone replacement treatments can be effective in enhancing fertility. Estimates suggest that fertility can be achieved in 75-80% of male patients. Therapies such as pulsed GnRH can also help stimulate ovulation in women. Assisted reproductive therapy is also an option for people with Kallmann syndrome who want to conceive.

Hoang Trang


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