Kleinfelter's syndrome, a sex chromosome abnormality that can be detected early by NIPT


To provide a clear explanation of meiosis and sex chromosome aberrations, we use the example of Klinefelter's syndrome.
I want you to know through this page that NIPT (new prenatal diagnosis) is suitable for early detection and treatment because the symptoms are less obvious.

Symptoms are difficult to recognize. Early detection method is NIPT (new prenatal diagnosis).

Klinefelter's syndrome is designated as an incurable disease.
Symptoms are not apparent in childhood.
In many cases, it is discovered after a visit to a fertility clinic.

Symptoms that are difficult to see and understand include

  • Tall (not extreme) azoospermia
  • The male hormone testosterone is not secreted.
  • Slight learning disability
  • Language development delay
  • Secondary sexual characteristics are difficult to see

These are difficult to determine by subjective symptoms and may not occur in everyone.
However, knowing about them during NIPT (new prenatal diagnosis) can help prevent the complications discussed below.

ICSI if natural conception is difficult

In recent years, it has become possible to have a child through ICSI even after a diagnosis of azoospermia.
This is because sperm can be retrieved by intra-ovarian sperm retrieval under a microscope.

A person diagnosed with azoospermia is unable to produce sperm because of damage to the testes.

However, there are parts of the testes that are not damaged as well.

The microscopic intracytoplasmic sperm retrieval is the process of finding undamaged areas under the microscope and taking sperm from them.

The recovered sperm are used for ICSI.

Meiotic failure is a chromosomal aberration.

Meiosis failure results in a change in the number of sex chromosomes.
The effect of the altered number of sex chromosomes is Klinefelter's syndrome.

Meiotic failure is the majority cause of Klinefelter's syndrome.

But doesn't this beg the question?

What is meiosis anyway?

What kind of chromosomes are sex chromosomes?

What is a failure when it happens?

The following items are intended to address these questions.

What is meiosis?

Division occurs twice before the sperm and egg are fertilized.
The two divisions cut the number of chromosomes in half.
The reason for halving the number of chromosomes is to prevent the number of chromosomes from continuously increasing with each fertilization.

If a sperm and an egg have one chromosome each, then after fertilization they have two chromosomes.
After fertilization, a child is born, and the child has two chromosomes.
What if, for example, meiosis does not occur?
Sperm and egg each have two chromosomes, right?
When a sperm with two chromosomes fertilizes an egg (with two chromosomes), the number of chromosomes increases to four.
In the next generation, the number of chromosomes is 8, and in the next generation, 16, 32, and 64.
Since the number of chromosomes in humans is 46, doesn't this mean that our ancestors have not been around for many generations?

The purpose of meiosis is to create sperm and eggs and pass them on to the next generation while maintaining a certain number of chromosomes.

What constitutes a meiosis failure?

Meiotic disjunction is when multiple chromosomes enter a cell that can only contain one chromosome. Meiotic disjunctions can occur in both the first and second mitosis.

If meiosis does not fail, the number of chromosomes that can enter one cell is one.
That cell is transformed into a sperm or an egg.

It is normal for humans to have two chromosomes once fertilized.

When meiosis fails, there are multiple chromosomes in one cell.
When these chromosomes are fertilized, they are different from the normal number, right?
This is the abnormal number of sex chromosomes.

Types of Chromosomal Aberrations

They are called differently depending on the number of sex chromosomes after fertilization.

Number of Chromosomes Designation

Dysomy is normal for humans, while Klinefelter's syndrome is trisomy and tetrasomy.

For example, replace meiotic inseparability with gender

To help visualize the non-separation of the reducible separation, we replace the following conditions

  • Chromosomes of female origin are female.
  • Chromosomes of male origin are male.
  • Cells are rooms.
  • Meiosis is originally two times, but in the example it is made once.

(1) The four women who were playing together are about to go home, and each of them intends to go back to their rooms.

(2) Two of the four of us decided we wanted to drink again, so we went back to the room together.

(3) Then you have one room with two people, two rooms with one person, and one room with no one in it.

(4) A man who lives with two women in a room with two women has returned.

(5) Is inseparable in meiosis.
(6) Is fertilization and trisomy.

In this example, it was caused by the female side, but it can also be caused by the male side.

Why meiotic disjunctions are bad

This is because the substance increases too much and causes problems in the body.

A higher than normal number of chromosomes also increases gene expression.
Gene expression is the production of hormones and other protein-based substances.

For example, let's replace it with cooking.

Seasonings are essential for seasoning, but too many can spoil the flavor.
A balance of seasonings is important for good food.

The same is true in the body, where various substances are balanced in moderation to maintain a healthy body.

Difference between chromosomes and sex chromosomes

A sex chromosome is one of the chromosomes.
Chromosomes are divided into sex chromosomes and autosomes.
Humans have two sex chromosomes and 44 autosomes.
Sex chromosomes are involved in sex determination, and the rest are called autosomes.

Sex chromosomes are represented by X and Y, where XY is male and XX is female.
XY and XX are the normal forms of sex chromosomes.

Klinefelter syndrome occurs only in males.
Having at least one Y chromosome and two X chromosomes is a requirement for Klinefelter's syndrome.

How to describe sex chromosome abnormalities

In much of the literature, only the number of chromosomes and sex chromosome phenotypes are described.

Sex chromosome aberration with 47 chromosomes and sex chromosome phenotype XXY.
This is hard to put in writing, so it is denoted by (47/XXY).

The normal sex chromosome phenotype is (46/XY).
The sex chromosome abnormality in Klinefelter's syndrome is mostly (47/XXY), although there is also (48/XXYY).

Why a high number of X chromosomes is not good

This is because gene expression is increased above normal, causing the body to malfunction.

Doubling the number of Xs does not double all of the gene expression in the Xs.
In humans and mice, all but one X chromosome is suppressed in gene expression, and which X chromosome is left is random.

This is called lionization (X-chromosome inactivation) and is performed to equalize the gene expression in males and females.
Lionization is the reason that sex chromosome aberrations are less life-threatening than autosomal aberrations.

That would seem to indicate that there is no problem, would it not?

However, there are areas of gene expression that are not repressed.
The pseudo autosomal region (PAR) is not suppressed.
It is the genes in the PAR that increase in expression in proportion to the number of X's.

One of the symptoms of Klinefelter's syndrome was your tall stature.
PAR has the SHOX gene, which affects height.
The symptoms of tall stature are caused by increased expression of the SHOX gene.

The failure of meiosis results in a change in the number of X chromosomes.
Depending on the number of X chromosomes, the normal gene expression level is not achieved, and various physical symptoms occur in Klinefelter syndrome.

Early detection with NIPT (new prenatal diagnosis) can help prevent complications

Symptoms of Klinefelter's syndrome can lead to a variety of complications.
Early detection and treatment with NIPT (new prenatal diagnosis) is effective in preventing complications.

Sex chromosome abnormalities cannot be symptomatically controlled without treatment.
Since sex chromosome abnormalities, as well as Klinefelter's syndrome, cannot be fundamentally cured, treatment is symptom relief.

Complications of Klinefelter's syndrome include


②Bone loss

③Muscle weakness

④Type 2 diabetes

⑤Malignant tumors (breast cancer is the most common)

Of these, (1) through (3) are complications caused by low testosterone.
Take preventive measures against complications by taking male hormones from puberty.
To do so, it is necessary to know if you have Klinefelter's syndrome by NIPT (new prenatal diagnosis).

(4) and (5) are complications that are congenital in patients with Klinefelter's syndrome.
These are lifestyle-related diseases.

Early detection by NIPT (new prenatal diagnosis) and careful lifestyle habits from infancy will lead to prevention.