Sex Selection to Prevent Sex-Linked Disorders: The Most Common Disorders and Prevention Strategies

Sex selection, often wrongly termed gender selection, is a process in which doctors and patients (couples/parents-to-be) are legally and ethically permitted to use IVF and associated ART techniques to select an embryo of a certain sex for transfer because of medical reasons. 

The most common medical reason to perform sex selection is to help parents from passing on their sex-linked disorders to their children. A sex-linked disorder is a common genetic disorder caused by or linked to gene(s) located on either of the sex chromosomes (X or Y).

There are hundreds of genes located on the X chromosome, however the Y chromosome is much smaller than the X chromosome and thus, carries relatively far fewer genes.

Disorders on the Y-Chromosome, such as Hypertrichosis of the ears, webbed toes, or porcupine man, can only be transmitted from father to son, since all male children will get the fathers Y chromosome, and all female children will get the fathers X chromosome. So, to avoid a Y-chromosome disorder then the solution is simple sex selection for a female child. 

Inheritance for disorders on the X-chromosome is much more complicated. The inheritance can happen in either a dominant or a recessive manner, dependent upon the disorder and the sex of the child.  

If on the fathers X-chromosome then likely the father will be affected, and that all his male children will be unaffected (they get his Y chromosome) and all female children will be carriers. So, where the father is a carrier on either chromosome X or Y, simple sex selection will remove the disorder (for a boy if the disorder is on the fathers’ X-chromosome, and for a girl if it is on the fathers Y-Chromosome).

If on one of the mother’s X-chromosomes, then;

1. 50% of male children will be affected, and 50% of male children will be unaffected
2. 50% of female children will be unaffected, and 50% of female children will be carriers
3. Further complicated for female carriers, where for some disorders they will be dominant carriers and affected, and for other disorders they will be recessive carriers and unaffected.

In this article, we will walk you through some of the most common X-linked genetic disorders and what you can do to protect your child from inheriting it.

The 5 Most Common X-Linked Genetic Disorders

1. Fragile-X Syndrome

Fragile X syndrome (FXS) is the most common form of inherited intellectual and development disability. The disorder mainly causes intellectual disability or a condition in which there are limits to a person’s ability to learn at an expected level and function in daily life. However, many times it also triggers various behavioral and medical issues including hyperactivity, hand flapping, hand biting, temper tantrums, and autism. 

The disorder is inherited in an X-linked dominant pattern, meaning basically it can affect both males and females (“dominant”) but will affect males more severely than females because females have another X chromosome to offset the damaged X (XX), while males have only one X chromosome (XY) no backup, and the symptom is fully and severely expressed. 

2. Duchenne Muscular Dystrophy

Duchenne muscular dystrophy (DMD) is a rare muscle disorder, but it is one of the most common and most severe genetic conditions in children. Duchene is caused by a mutation in the DMD gene on the X-Chromosome. This mutation prevents the body from producing dystrophin, a protein that muscles needs to work properly. Without dystrophin, almost every muscle cell become damaged and weakened, and will deteriorate over time to the point where children will usually end up needing assisted ventilation and face premature death. The disorder is a multi-systemic condition, meaning if affects many parts of the body, whether it be the skeletal, heart or lung muscles.

The disorder is inherited in an X-linked recessive pattern, meaning basically that it will usually only affect males, with females only a “carrier.” The word “recessive” refers to a situation where a mutation would have to occur in both copies of the gene to cause the disorder, and because it is unlikely that a female will have two altered copies of such a gene, she will usually at worst end up being a carrier.

3. Hemophilia 

Hemophilia is an inherited bleeding disorder in which blood does not clot normally when there is a wound or injury, causing one to bleed longer than other people. The bleeding can occur internally, within joints and muscles, or externally, from minor cuts, dental procedures, or injuries. According to the Centre for Disease Control and Prevention (CDC), “Hemophilia occurs in about 1 out of every 5,000 male births” and “death can occur if the bleeding cannot be stopped or if it occurs in a vital organ such as the brain.”

Like DMD, Hemophilia is inherited in an X-linked recessive pattern, meaning basically that it will usually only affect males, while females are only a “carrier.” 

4. Red-Green Color Blindness

Red-green color blindness, also known as deuteranopia, is the most common type of color deficiency. People with red-green color blindness find it hard to tell the difference between red and green and their whole color spectrum is then often affected. 

Like DMD and Hemophilia, red-green color blindness is inherited in an X-linked recessive pattern, meaning basically that it will usually only affect males, while females are only a “carrier.” 

5. X-Linked Agammaglobulinemia 

X-linked agammaglobulinemia, or XLA, is a genetic immune system disorder. Children born with XLA have very few B cells, which are crucial white blood cells to protect their body against infections. This results in infections taking longer to get cured and often recurring even with antibiotic medications. Individuals with XLA are more susceptible to infections because their body makes very few antibodies. The most common bacterial infections that occur in people with XLA include lung infections (pneumonia and bronchitis), ear infections (otitis), pink eye (conjunctivitis), sinus infections (sinusitis) and chronic diarrhea. Recurrent infections can lead to organ damage.

The disorder is inherited in an X-linked recessive pattern, meaning basically that it will usually only affect males, while females are only a “carrier.” 

Treatment Approaches: IVF, PGT-M, PGT-A for Sex Selection

Most of sex-linked genetic disorders are incurable, but they are certainly preventable. 

For disorders carried by the father, we can use IVF together with Pre-implantation Genetic Testing for aneuploidy (PGT-A), to choose a euploid (correct number of chromosomes) of the right sex. So, where the father is a carrier on either chromosome X or Y, simple sex selection will remove the disorder (for a boy if the disorder is on the fathers’ X-chromosome, and for a girl if it is on the fathers Y-Chromosome).

For disorders carried by the mother, we can use IVF together with Pre-implantation Genetic Testing for monogenetic disorders (PGT-M), to select and transfer only an embryo or embryos that are free or unaffected by your hereditary condition. For X-linked recessive conditions that also allows transfer of female carriers, while for X-linked dominant conditions female carriers cannot be transferred. PGT-M (previously known as PGD) is an early genetic diagnosis test for embryos produced during IVF, prior to their transfer to the uterus. At Superior A.R.T, we use Karyomappping, the latest technology for PGT-M which requires only 1-3 weeks to complete a test workup, unlike other PGT-M tests that usually take months to finish, and has reported higher reliability and accuracy. With Karyomappping, DNA fingerprints of embryos and family members will be compared to determine which embryos are free from the disorder. To learn more about our unique PGT-M and Karyomappping, click here.

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