Rare Genetic Conditions That Can Cause Male Infertility!

Most of us know that DNA is the fundamental building block of life, and even a small alteration to it can have a significant impact on how our body functions, responds, or behaves. However, what may come as a surprise is that such minor modifications or alterations in the genetic material (DNA) can also affect your fertility!¹ Sounds surprising? This blog will put all your questions to rest! So, without further ado, let’s learn about some rare genetic conditions that can cause male infertility. 

4 Lesser-Known Genetic Conditions That Can Cause Male Infertility 

A genetic condition, also known as a genetic disease, results from a change or alteration in an individual's genetic material or DNA sequence, which can be caused by a mutation.² Moreover, genetic conditions can be both inherited (from parents to children) or could occur denovo* ( mutation not present in parents).³ 

*A genetic mutation present for the first time in the family.

So let’s take a look at the rare disorders that can cause male infertility.

1. Androgen Insensitivity Syndrome

Androgen insensitivity syndrome (AIS) is a rare X-linked genetic condition that affects a person's sexual development. In this condition, a specific mutation linked to the X-chromosome inhibits the body's response to the male hormone - androgen. Despite having both X and Y chromosomes, individuals with AIS do not display typical secondary male sexual characteristics, such as visible facial hair or a deep voice. Instead, they may exhibit pronounced female-like traits or a combination of male and female traits.^4,5 

AIS has two types listed below:

i. Complete Androgen Insensitivity Syndrome (CAIS)

Complete androgen insensitivity syndrome (CAIS) occurs when the body develops complete androgen resistance. Individuals with CAIS exhibit fully feminized characteristics such as breast development, but have an absence of a uterus and/or ovaries. They also have undescended testicles and elevated testosterone levels.⁶ 

CIAS affects 2-3 out of every 1,00,000 genetically “male individuals,” making it one of the rarest genetic conditions that can cause male infertility.⁶ 

ii. Partial Androgen Insensitivity Syndrome (PAIS)

PAIS is caused by the body’s partial or comparatively low sensitivity to androgen. Individuals with this genetic condition have genital organs that resemble either male or female sexual organs. However, in some cases, they have genitalia with both male and female characteristics.⁴

In contrast to complete AIS, individuals with PAIS exhibit both male and female characteristics. They may even have a short vagina, partial closure of the outer vagina, and an enlarged clitoris. This condition does not typically cause infertility, as individuals with PAIS typically have a functional reproductive system.⁵

Individuals with AIS exhibit following characteristics:⁵

• Vagina without uterus or cervix
• Inguinal hernia (when organs protrude through the skin at the abdominal region⁷)
• Grown female breasts
• Undescended testes or testes present at an anatomically wrong position

As AIS restricts the growth of male sex organs, individuals born with AIS are infertile.

2. Disorders Of Sexual Differentiation

Disorders of sexual differentiation (DSD) is an umbrella term for conditions that affect the body's sexual development. Individuals with sexual differentiation have either undefined sexual organs or genitals of both genders.⁸ These conditions are also known as “intersex disorders” or “ambiguous genitalia” because determining a person's gender solely based on physical examination is difficult.^8,9 

Males with ambigous genitalia, a result of disorder of sexual differentiation may have:⁸

• Hypospadias (congenital birth defect in which the tip of penis doesn’t have urethera opening)
• Small penis
• Small or undefined scortum
• Undescened testicals

DSDs are congenital, meaning they occur at birth and result from abnormalities during the development stage of reproductive organs inside the womb. However, these abnormalities can also arise due to high exposure to male hormones in the womb.⁹ 

Some sexual differentiation disorders can be diagnosed by examining the patient’s genitalia. Signs associated with these disorders include:^9,10

• Ambiguous genitalia, a rare condition where the external genitals do not appear to be male or female. Newborns with ambiguous genitalia may be incompletely developed or have characteristics of both sexes.¹¹
• Absence of sexual characteristics such as reproductive organs
• Delayed puberty or abrupt changes during puberty
• Enlarged clitoris (female sex organ that is located in the above region of vagina)
• Issues with adrenal glands
• Undescended testes

Individuals with sexual differentiation disorders may also have other congenital problems, such as developmental delays and deformities in the hands, feet, legs, and so on.¹⁰

3. Hypogonadotropic Hypogonadism

Hypogonadotropic hypogonadism (HH), also known as Kallmann syndrome (when inherited), is a type of hypogonadism that affects the function of the pituitary gland in men.^11,12 

HH can occur as a congenital condition, as well as due to external factors such as:¹²

• Abrupt weight loss or gain
• Drug abuse
• Damage or injury to pituitary gland
• High prolactin levels
• High/severe stress levels
• Prolonged use of high doses of opioids

Symptoms

In adults, HH can be diagnosed by looking for certain warning signs listed below:¹²

• Decreased libido in men
• Fatigue 
• Inconsistent moods
• Infertility 

4. Syndromic Causes Of Infertility

Syndromic disorders encompass another set of genetic conditions that can cause male infertility. The term “syndromic” refers to a collection of signs, symptoms, and clinicopathological characteristics that may or may not have a genetic basis, defining an abnormal condition as a whole.¹³

Two major types of genetic condition that can cause male infertility are:¹⁴ 

i. Single Gene Defects

Mutations or changes that occur in genetic material (DNA) that codes for a particular gene can often lead to genetic conditions that can cause male infertility. Some of these genetic conditions are listed below:¹⁴

• Canavan disease
• Cystic fibrosis
• Tay Sachs disease
• Thalassemia
• Sickle cell anemia
• Spinal muscular dystrophy

ii. Chromosomal Abnormalities

Chromosome abnormalities are caused by abnormalities or changes in the number, structure, or position of the “chromosomes,” which carry our DNA.¹⁴ Similar to single gene defects, chromosomal abnormalities also give rise to genetic conditions that can cause male infertility. Such genetic conditions that may affect fertility include:¹⁴

• Down syndrome: A common genetic disorder caused by mutations in chromosome 21. Chromosomes are the bearers of genomic information and are responsible for all inherited features such as height, eye colour, and so on.¹⁵ 
• Klinefelter syndrome: Men usually have two sex chromosomes i.e., “X” & “Y.” However, individuals with Klinefelter syndrome have one extra “X” chromosome.¹⁶ 
• Turner syndrome: A condition wherein females are born with complete or partial absence of X chromosome.¹⁷ 

You've already learned about some lesser-known genetic conditions that can lead to male infertility. However, in order to determine the exact cause of one’s inability to have children, a deeper examination, such as genetic testing may be required. And that’s where the need for tests like LifeCell’s InferGenes arises!

InferGenes- Male Test: Your Diagnosis Partner!

“InferGenes- Male” Test can help you find answers for unknown male infertility and related concerns that may be caused by genetic conditions. It enables individuals struggling with infertility to gain a better understanding of their condition. To take LifeCell's InferGenes test, simply order the kit online, collect your saliva sample, schedule a prepaid sample pick-up and our team of experts will take care of rest! 

Moreover, we use the NGS technique to examine “36 genes” that can aid in diagnosing conditions that may cause male infertility. These conditions include cystic fibrosis, congenital bilateral absence of the vas deferens, adrenal insufficiency, congenital adrenal hyperplasia, persistent Mullerian duct syndrome, among others. 

In addition to embarking on your reproductive journey, you could have your own reason to take the InferGenes test. At LifeCell no questions are asked! However, if you or your partner have recently encountered any of the situations listed below, selecting InferGenes would be a good idea.

1. Family history of genetic conditions or diseases
2. Abnormal semen analysis results
3. Abnormal hormone test results

Taking LifeCell’s InferGenes will automatically qualify you for valuable insights from our experts on how to manage your genetic condition (if any, as per the test result). Not only that, but you’ll also receive expert genetic counseling, which will assist you in taking appropriate steps for the future.

In Conclusion

Having a genetic condition does not always result in obvious signs of a disorder. In many cases, individuals may only carry a “carrier gene” for a specific genetic condition, which means that they may or may not have the disorder but may pass it on to their children.¹⁸ And this is why genetic testing, such as InferGenes is essential, particularly for those who have been repeatedly unable to conceive or are planning to start a family.

Curious to learn more? Call us at 1800 266 5533