Overview

Kallmann Syndrome (KS) is a rare genetic disorder characterised by anosmia (lack of smell) and absent or delayed puberty.¹ KS is a type of hypogonadotropic hypogonadism (HH).² HH is a group of conditions where the body does not make enough of the hormones responsible for sexual development.¹ In the case of KS, there is a lack of gonadotropin-releasing hormone (GnRH).² GnRH is produced in the brain, in a region called the hypothalamus. GnRH signals the pituitary gland to release two key hormones: follicle-stimulating hormone (FSH) and luteinising hormone (LH). FSH and LH signal the testes in people assigned male at birth (AMAB) and the ovaries in people assigned female at birth (AFAB) to produce sex hormones. For people AMAB, this is testosterone, and for people AFAB, this is oestrogen. Therefore, GnRH is responsible for sexual development and the onset of puberty. In people AFAB, GnRH is important for the regulation of ovulation.³ 

KS is thought to affect 1 in 8000-10,000 people AMAB and 1 in 50,000 people AFAB.² Due to the rare nature of the disorder, it can be difficult for patients to understand what is happening. Puberty tends to affect individuals differently; some young people start puberty earlier than others. Therefore, diagnosis occurs a lot later with KS as patients can often be considered ‘late bloomers’. However, dealing with being ‘left behind’ compared to their peers can often leave patients feeling shame and fear. Many have imposed isolation on themselves to hide their delay in puberty.⁴ This has a disproportionate impact on social well-being and self-esteem. 

This article will explore KS in more detail, the psychological effects associated with the condition and available treatment options and coping strategies.

Understanding the condition

Biological aspects of KS

KS is characterised by a reduced or complete loss of smell and GnRH deficiency.⁵ The dysfunction caused by the inadequate production of GnRH causes a delay or an absence of puberty.¹ KS has a genetic component and can be passed down from parents to children. KS can be transmitted through three forms: X-linked recessive, autosomal dominant or autosomal recessive inheritance. This means KS can be passed down from one or both parents. However, most cases of KS are sporadic, with no clear link to family history.⁵ 

KS is more common in people AMAB. One reason is that a mutation in the ANOS1 gene, located on the X chromosome, is a common cause of KS.² This is more likely to affect people AMAB because they only have one X chromosome in their cells. People AFAB have two X chromosomes, so if one X chromosome shows the mutation, the other usually can compensate. Moreover, in people AFAB who may have KS, their symptoms can be more difficult to detect or are often overlooked. Some symptoms that are displayed can also be milder compared to people AMAB who are affected by KS.⁵ 

How is KS diagnosed?

KS is usually diagnosed during adolescence, when a child fails to display the usual signs of the onset of puberty, but this can be overlooked, and the diagnosis could be delayed due to the highly variable manner this period develops in every individual. At this stage, constitutional delay in growth and puberty (CDGP) also affects 2.5% of the general population.¹ It is, therefore, often difficult to determine whether the onset of puberty will occur, just at a later stage or if the child will not undergo puberty at all. However, if there is a family history, the diagnosis may occur earlier. Some people AMAB with KS are sometimes born with cryptorchidism (undescended testicles) and a micropenis.² 

KS can present with other traits. The most commonly associated characteristic is the loss of smell, affecting about 60% of the patients.² Other traits are shown in Tables 1 and Figure 1, respectively. In some cases, diagnosis does not occur until late adulthood, when an individual experiences infertility. 

Table 1: Table 1 shows the differences in signs of delayed or absence of puberty by gender¹

Methods of diagnosis

When a delay in puberty occurs, parents often raise initial concern. A diagnosis generally takes place after ruling out other possible cases, such as CDGP – which is not associated with a lack of a sense of smell, a typical hallmark characteristic of KS. Moreover, in KS, patients may present with cryptorchidism, micropenis or a cleft lip or palate.² This can help to rule out other causes of delayed puberty.

Anosmia (lack of sense of smell) can often be seen on a magnetic resonance imaging (MRI) scan, which would show underdeveloped or affected regions of the brain responsible for the sense of smell, known as the olfactory bulb.^2,5

Laboratory testing can also help with diagnosis, as it can test for hormone levels. In people AMAB, KS will present with low levels of testosterone and in people AFAB, oestrogen levels will be low. Regardless of gender, affected people will have low levels of LH and FSH.²

Psychological effects of delayed puberty

Body image concerns

There are several psychological effects caused by delayed puberty. In individuals with KS, since diagnosis often occurs around adolescence, there is a common feeling of being left behind. With delayed puberty, healthcare professionals often take on an observer approach, which is waiting for the child in question to eventually experience puberty.¹ This is because CDGP is more common and thus more likely to occur. When there is a continued absence of puberty, healthcare professionals will start to factor out causes and determine a diagnosis. However, this diagnosis delay can cause young people to lack an understanding of what is happening to them. These numerous questions, with no answers, can make young people feel dismissed.¹ To label them as ‘late bloomers’ and not consider other factors may cause teenagers to feel neglected by healthcare professionals and like they are not taken seriously.¹ This uncertainty, exemplified by their peers achieving key milestones, can lead to feelings of low self-esteem and shame. 

Social anxiety

It can be very difficult to want to be involved in social events or any environment, interacting with peers, when the shame and embarrassment of not starting puberty or showing any signs of puberty can affect teenage relationships. In a study, it was found that participants with KS who were diagnosed later often found that they missed out on development that generally occurs in those teenage, formative years. One participant stated, “I was diagnosed at 23. So that’s why I say I ‘missed out’ on that…emotional and physical development”.⁴

Emotional distress

Experiencing delays in puberty can be frustrating and quite scary for teenagers. Puberty is something that everyone experiences, which may make teenagers experiencing delays feel afraid of what this means for them. This can feel even worse when a delay in a diagnosis occurs, especially when considering how reluctant one may feel to share a condition they may consider to be embarrassing. Since KS is a rare disorder, as is common with most rare disorders, delays or incorrect diagnoses do occur.¹ This can affect the trust a teenager may have in the healthcare system as a whole, as well as affect the trust they may have for healthcare professionals. 

Psychological impact of infertility

Infertility is associated with KS due to a deficiency in sex hormones.⁶ The psychological impact of infertility is vast; it is linked to long-term mental health risks such as anxiety and depression, and plays a role in low self-image and self-esteem issues.⁷

Individuals with KS who suffer from infertility may experience a sense of grief and loss, especially if they expected or wanted biological children. The lack of choice in that matter can cause a significant blow and be very painful. In a study conducted on young girls diagnosed with hypogonadotropic hypogonadism (HH), one key fear was infertility, and both the parents and the girls were “devastated”.⁸

In romantic relationships, those with KS may fear rejection or may struggle to find a suitable partner.⁷ This can cause low self-esteem, emotional distress and a decrease in quality of life. 

Coping strategies and psychological support

Medical interventions

There are various treatment options available that can significantly improve the quality of life. Hormone therapy is utilised to induce puberty and the formation of secondary sexual characteristics in young people diagnosed with KS.⁶ In people AMAB, this is testosterone therapy, and in people AFAB, it is oestrogen therapy. Lifelong hormonal therapy is needed to ensure the right amount of hormones is being produced. This is also important for bone density, as a deficiency in sex hormones is linked to diseases like osteoporosis.²

Fertility-based treatment options include gonadotropin therapy. Most patients seeking fertility treatments present a good response. However, in some cases, individuals remain infertile despite adequate intervention.²

Psychological therapy

Due to the impact of a disorder like KS, therapy and counselling treatments are necessary.² KS can be a very distressing condition. For young people who have been diagnosed and adults alike, it is important to seek help. It is normal to feel frustrated or scared of the impact KS may have on the future. It is important to speak to a healthcare professional so they can provide support with treatment options.

Summary 

Kallmann syndrome is a rare disorder that causes a delay or absence in puberty and is also usually associated with a lack of a sense of smell. This is caused by a deficiency in the sex hormones. For those facing this, it can be distressing. Fortunately, there are many treatment options available. With a diagnosis, the right care and treatment, quality of life can improve.