Kallmann Syndrome

Kallmann syndrome (KS) is a genetic disorder that delays puberty and may affect your sense of smell (anosmia). It happens when certain genes change during fetal development. Biological parents can pass the genetic change down to their children. But the gene changes may happen for no known reason.

The condition is more common in males than females. When puberty doesn’t begin in adolescence, your child’s healthcare provider may start to look for possible causes. For this reason, most people are between the ages 8 to 15 when they receive the diagnosis.

Healthcare providers may call this a form of hypogonadotropic hypogonadism. Hypogonadism is when your testicles or ovaries don’t produce the usual amount of sex hormones.

Symptoms of Kallmann syndrome

The syndrome can cause a range of symptoms that may appear in childhood or adulthood:

• Lack of breast development (girls)
• No periods or significantly delayed periods (girls)
• Small penis and testicles (boys)
• Infertility (boys and girls)
• Balance issues
• Cleft palate
• Dental abnormalities (such as missing teeth or unusually small teeth)
• Eye movement disorders (like nystagmus)
• Fatigue
• Irregular periods (in women)
• Low sex drive
• Loss of sense of smell (anosmia)
• Mood changes
• Renal agenesis (missing kidney)
• Scoliosis
• Weight gain

Sometimes, it doesn’t affect your sense of smell.

Kallmann syndrome causes

Changes in certain genes cause the syndrome. These changes, or variations, disrupt the process that drives puberty. This process begins when your child’s hypothalamus gland makes gonadotropin-releasing hormone (GnRH). In Kallmann syndrome, your child’s hypothalamus doesn’t make enough GnRH. Without this signal, puberty doesn’t begin.

GnRH supports sexual maturity, sex drive and fertility. Blood vessels carry the hormone to your pituitary gland (part of your brain). GnRH tells your pituitary gland to make two more hormones:

• Follicle-stimulating hormone (FSH)
• Luteinizing hormone (LH)

Some of the gene changes also affect how your child’s brain processes smells. Normally, olfactory nerve cells detect and send information about smells to their olfactory bulb. With Kallmann syndrome, these signals don’t reach your child’s brain.

This can lead to a reduced or absent sense of smell. If your child’s sense of smell isn’t affected, their healthcare provider may call their condition normosmic idiopathic hypogonadotropic hypogonadism (nIHH).

Researchers have identified more than 25 genetic changes that cause Kallmann syndrome and other types of hypogonadotropic hypogonadism. Research shows the following genes are most often linked to the condition:

• KAL1 (ANOS1)
• CHD7
• FGFR1
• GNRHR
• IL17RD
• PROK2
• SOX10
• TACR3

The gene changes happen during fetal development. Sometimes, the changes happen for no known reason. But children can inherit the changes from their biological parents.

Researchers have identified different ways a person can inherit these gene variations from their biological parents (inheritance patterns). Inheritance patterns in the syndrome are:

• Autosomal recessive inheritance, which means both parents carry some genetic variations
• Autosomal dominance inheritance, which is when one parent passes a genetic variation to their children
• X-linked inheritance, which means both parents pass the gene variation to their children in genes on the X chromosome

Kallmann syndrome complications

Puberty is an important milestone in child development. Kallmann syndrome can keep your child from reaching that milestone. It can delay or prevent your child’s sexual development. Your child may not go through the same physical changes as their peers. That can cause depression or anxiety.

How doctors diagnose Kallmann syndrome

Pediatricians start with a physical exam. They’ll ask your child and you about changes that typically happen when children are ages 8 to 15. They may ask if any family members went through puberty later than usual or didn’t go through it.

They may do the following tests if they think your child may have the syndrome:

• Blood tests to check hormone levels
• Tests to check your child’s sense of smell
• Genetic tests for specific genetic variations

How is Kallmann syndrome treated?

Hormone replacement therapy is a common treatment. The specific treatments will vary, but may include:

• Testosterone injections, skin patches or skin gels for males
• Estrogen and progesterone pills or skin patches for females
• GnRH injections to bring on ovulation or periods
• HCG injections (human chorionic gonadotropin) to boost testosterone and sperm in males and increase the chance of pregnancy in females

What can I expect if my child has this condition?

Your child may always need hormone replacement therapy. That said, infertility in males with the syndrome may go away. Healthcare providers may call this reversible Kallmann syndrome.