What is Kallmann syndrome?

This is the 2828th article of Da Yi Xiao Hu

Xiao Wang's experience

At that time, Xiao Wang was a junior in college at the age of 22. He was 1.6 meters tall, with long limbs, but he looked strong and sturdy. He was born with a baby face and fair skin. However, although Xiao Wang looked normal, he was weak and insensitive to smells.

What puzzles Xiao Wang even more is that he has not experienced puberty even after growing up. He has no beard, no armpit or pubic hair, and a very small Adam's apple. What makes Xiao Wang even more inferior is that his important organs are still like those of a child. This puts an increasingly heavy psychological burden on him. He is afraid of being noticed by others, so he dares not interact with girls. His personality becomes more and more withdrawn and silent.

Later, he finally plucked up the courage to go to the hospital for treatment. After careful examination by the doctor, it was diagnosed that Xiao Wang suffered from a congenital disease called "Kallmann syndrome".

What is Kallmann syndrome?

Kallmann syndrome is a type of hypogonadotropic hypogonadism with hyposmia or anosmia, and is a clinically and genetically heterogeneous disease. Kallmann syndrome can be familial or sporadic, and there are three ways of inheritance: X-linked recessive inheritance, autosomal recessive inheritance, and autosomal dominant inheritance. The epidemiological characteristics of the disease are still unclear, and it is roughly estimated that the incidence rate in boys is 1/8000, and the incidence rate in girls is about 1/5 of that in boys.

What are the symptoms of Kallmann syndrome?

1. Hypogonadism

Most male patients have a lower body that is larger than the upper body, a eunuch-like body shape, immature external genitalia, a short penis, small testicles or cryptorchidism, and lack of secondary sexual characteristics during puberty (no beard, armpit hair, pubic hair growth, no voice change). Female patients have dysplastic internal and external genitalia, no breast development during puberty, no armpit hair, pubic hair growth, and no menstruation.

2. Loss or decreased sense of smell

Patients experience complete anosmia, inability to distinguish between sweet and odorous smells, but some patients may only experience a decreased sense of smell.

3. Related physical abnormalities

In addition to gonadotropin-releasing hormone deficiency and anosmia, Kallmann syndrome is associated with a variety of physical abnormalities, including midline facial defects such as cleft palate and cleft lip, short metacarpal bones, and renal abnormalities. Neurological manifestations include sensory hearing loss, mirror movements (synkinesis), eye movement abnormalities, and cerebellar ataxia. To date, renal abnormalities and mirror movements have only been found in X-linked Kallmann syndrome.

How is Kallmann syndrome treated?

Currently, the main treatment options for Kallmann syndrome in men are:

1. Androgens

For patients who do not have the desire to have children for the time being, androgen treatment can be given after the age of 14 to promote the development of male secondary sexual characteristics, maintain normal sexual function, bone density, and body fat composition, and help maintain normal emotions and cognition. However, androgen treatment cannot restore fertility.

2. Gonadotropin

Gonadotropin therapy may restore fertility in patients, and studies have shown that the median time to sperm production is 7 months.

3. Gonadotropin-releasing hormone pulse therapy

When the anterior pituitary function is normal, gonadotropin-releasing hormone pulse therapy can be considered. Studies have reported that after 12 months of gonadotropin-releasing hormone pulse therapy, the sperm production rate of patients can reach 77%.

For female patients, when there is no desire to have children, cyclical estrogen-progestin combined replacement therapy can be given to promote the development of secondary sexual characteristics. If there is a desire to have children, gonadotropin ovulation induction therapy or gonadotropin-releasing hormone pulse therapy can be performed.

Author: Baoshan Branch of Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine

Dr. Xia Lemin, MD, Department of Hematology