Klinefelter’s Syndrome: The Complete guide

What is Klinefelter’s Syndrome

Kallmann Syndrome (KS), or otherwise known as anosmic hypogonadism, is a rare genetic condition whereby the body does not make enough gonadotropin-releasing hormone (GnRH), a hormone required for the production of sex hormones in both genders.^1,2 If left untreated, people with Kallmann Syndrome will remain sexually underdeve loped, and infertile.

There are two distinct features of Kallmann Syndrome that physicians look out for when prompting for diagnosis:

• A lack of physical change / sexual development associated with puberty.
• An impaired or absent sense of smell.

Gonadotropin-releasing hormone causes the pituitary gland in the brain to make and secrete the hormones luteinizing hormone (LH) and follicle-stimulating hormone (FSH). In men, these hormones cause the testicles to produce testosterone; and in women, they cause the ovaries to make oestrogen and progesterone.³

A deficiency in GnRH is associated with a normal sense of smell in approximately 40% of affected individuals and an impaired sense of smell in approximately 60%. Only when the sense of smell is affected can it be classified as Kallmann syndrome.⁴

Symptoms

From birth, males may exhibit features such as micropenis or undescended testicles, signalling early signs of the condition. However, the most noticeable symptoms typically arise at puberty due to the lack of sexual maturation.1,2,5

Symptoms in Males:

• Little to no testicular growth.
• Decreased bone density.
• Reduced muscle mass.
• Erectile dysfunction.
• Low libido.
• Infertility.
• Micropenis.
• Undescended testes.

Symptoms in Females:

• Amenorrhea (absence of menstrual periods).
• Insufficient breast development.
• Infertility.

Symptoms Affecting Both Genders:

• Impaired or absent sense of smell (anosmia or hyposmia).
• Delayed or absent puberty signs.
• Decreased bone density (increasing the risk of osteoporosis).
• Non-reproductive features that may be present include:
• Cleft lip or palate.
• Hearing impairment.
• Skeletal anomalies such as shortened digits.
• Dental anomalies.
• Ocular motor disturbances.
• Renal anomalies.

Diagnosis

So how do you tell the difference between these clinically identical conditions? Well, due to the noticeable lack of sexual development, diagnosis of Kallmann Syndrome is typically made by an endocrinologist when examining a patient going through puberty. However, signs such as undescended testicles or a small penis in infancy can also prompt early investigation.^1,2

An endocrinologist can confirm a diagnosis through clinical examination, blood testing, imaging, and using the Tanner staging tool – an established diagnostic method used in the field of endocrinology to determine the development stage of certain sexual characteristics. In some cases, genetic testing may be requested to further assist in diagnosing various forms of this disease. ⁵

Treatment

Currently there is no cure for Kallmann Syndrome, but there are treatments that are effective at managing the disease.² Treatment is usually lifelong and involves hormone replacement therapy, with further options available for those seeking fertility. Without treatment, most affected men and women are unable to have biological children due to infertility.¹

However, getting the right treatment for Kallmann Syndrome can at times be difficult, given the rather private nature of the disease. This has led to a cultural hesitancy among many UK doctors to initiate discussions about hypogonadism, which inadvertently causes delays in treatment. This reluctance can make it challenging for patients to seek help, with some individuals only receiving treatment to induce puberty in their 40s.⁷

Learn more about hypogonadism: The Complete Guide

On the contrary, Kallmann Syndrome is considered a lifelong condition, about 10-15% of patients may experience spontaneous recovery of their hormonal system, though the reasons for this remain unclear.⁵

Kallmann syndrome is not associated with decreased life expectancy and treated individuals have a normal appearance and function that is indistinguishable from individuals without the condition.6 Untreated, the condition can lead to various complications in adulthood, including decreased bone density, muscle mass, infertility, erectile dysfunction in males, and abnormal menstruation (amenorrhea) and insufficient breast development in females.

Prognosis

Currently there is no cure for Kallmann Syndrome, but there are treatments that are effective at managing the disease.² Treatment is usually lifelong and involves hormone replacement therapy, with further options available for those seeking fertility. Without treatment, most affected men and women are unable to have biological children due to infertility.¹

However, getting the right treatment for Kallmann Syndrome can at times be difficult, given the rather private nature of the disease. This has led to a cultural hesitancy among many UK doctors to initiate discussions about hypogonadism, which inadvertently causes delays in treatment. This reluctance can make it challenging for patients to seek help, with some