Kallmann Syndrome - Symptoms, Causes, and Treatment

What Is Kallmann Syndrome?

Kallmann syndrome (KS) is a congenital condition characterized by a hormonal imbalance that results in hypogonadotropic hypogonadism (HH) and a loss of smell. It begins at birth and is caused by a lack of gonadotropin-releasing hormone (GnRH). Due to a lack of sexual development, Kallmann syndrome is frequently diagnosed during adolescence. The majority of cases of Kallmann syndrome are not hereditary, although some are. The mode of inheritance is defined by the gene involved. Hormone replacement therapy for sexual development is the mode of treatment. In most cases, fertility can be attained.

What Are the Symptoms of Kallmann Syndrome?

Kallmann syndrome (KS) is not a life-threatening disorder. The main symptoms are as follows-

• Delayed or absent signs of puberty.

• Absent sense of smell (anosmia).

• A diminished sense of smell (hyposmia).

• Undescended or partially descended testicles in males.

• The small size of the penis.

• Facial defects like cleft lip or palate.

• Short fingers and toes (especially the fourth finger).

• Development of only one kidney

• Hearing loss.

• Color blindness.

• Abnormal eye movements.

• Abnormal teeth development.

• Mirror hand movements (bimanual synkinesis).

• Females have delayed breast and pubic hair development and no menstruation.

• If not treated, both males and females can become infertile.

• Neural hearing impairment.

• Cerebral ataxia (poor balance or coordination).

• Eye defects such as coloboma or ptosis.

• Increased incidence of color-blindness.

What Are the Causes of Kallmann Syndrome?

The condition known as normosmic idiopathic hypogonadotropic hypogonadism (nIHH) occurs when a person has a hormone deficiency characteristic of Kallmann syndrome but has a normal sense of smell.

Kallmann syndrome is a genetic disorder caused by mutations in a variety of genes, some of which have been identified and inheritance patterns mapped. Kallmann syndrome is caused by a variety of gene mutations that have different inheritance patterns.

The following types of inheritance can be seen,

1. Autosomal Recessive Inheritance - Some genes are passed down through both parents. Both parents may be carriers in these cases, meaning they have no symptoms of the disease.

2. Autosomal Dominant Inheritance - Genes inherited from either the mother or the father.

3. X-Linked Inheritance - Males have (express) the condition, while females are carriers. The condition can be passed down from mothers to sons, but not from fathers to sons in these cases. As a carrier, either parent can pass the disease to a daughter.

4. Oligogenic Inheritance - Mutations in more than one gene may combine to cause the condition.

How Is Kallmann Syndrome Diagnosed?

• Signs and symptoms related to delayed puberty and impairments to the patient's sense of smell are observed. The doctors may perform a physical examination.

• As this is an inherited condition, the doctor may inquire about relatives who have had problems with fertility or puberty.

• With evidence of sexual maturation or hypogonadism and Tanner staging (Tanner staging is a well-established method for evaluating the development of primary and secondary sexual characteristics that endocrinologists use all over the world), evidence of incomplete sexual maturity, Kallmann syndrome may be suspected.

• Other tests include,

  • Olfactory Function Testing - It involves the evaluation of the sense of smell.

  • Blood tests look at hormone levels in the pituitary gland's peripheral veins.

  • Anatomical abnormalities in the hypothalamus, pituitary gland, and nose are investigated using magnetic resonance imaging (MRI).

  • Testing for specific gene mutations using molecular genetics.

What Is the Treatment for Kallmann Syndrome?

The following measures can be taken to manage Kallmann syndrome -

• Hormone replacement therapy is used to treat Kallmann syndrome, with medications and doses tailored to the patient's needs. The first goal of this treatment is to induce puberty and maintain normal hormone levels. It is also possible that the treatment will be changed later to induce fertility.

• Infertility in males with Kallmann syndrome is caused by a lack of sperm production in the testis. GnRH administered via a micro infusion pump or gonadotropin injections can both be used to produce sperm.

• Infertility is caused by a lack of maturation of eggs within the ovaries in females with Kallmann syndrome. Ovulation induction can be accomplished with either pulsatile GnRH therapy or gonadotropin injections given at predetermined intervals to initiate the maturation and release of the egg for natural conception.

• Medication may also be required to restore bone health, as the same lack of hormones that causes delayed puberty can also cause bone density and strength to deteriorate.

• When medication is used to supplement hormone production, it is necessary to conduct periodic follow-up tests to ensure that the treatment is still effective. Over time, dosage levels and medication combinations may need to be tweaked.

• There is no cure for lack of a sense of smell. Being unable to smell properly can be dangerous, as the person will be unable to detect smoke or recognize when food has gone bad.

What Are the Complications of Kallmann Syndrome?

• A small subset of patients with Kallmann syndrome has been reported to have a variety of congenital heart disorders.

• Bony disorders like osteoporosis (a condition in which the bones become brittle and weak) or osteopenia (when the body fails to make new bone as quickly as it reabsorbs old bone).

• A developmental bone malformation, such as a cleft palate, is also possible and would be recognized from birth.

• Hypogonadic conditions like Kallmann syndrome can also cause dry skin as a side effect.

• A patient may have adrenocortical insufficiency as a child or adolescent.

Conclusion

Kallmann syndrome is an inherited disorder in which the body produces insufficient sex hormones. The sense of smell is also affected by Kallmann syndrome. If the child is not treated, they will not reach puberty and become infertile. Long-term hormone therapy is required for normal growth and development and to avoid infertility. Although Kallmann syndrome is not linked to a shorter life expectancy, it is linked to heart disease, osteoporosis, and reduced fertility, which may impact the patient's health and longevity.