India’s genetic disorders: prevalent kinds, risk factors, and stopping transmission

The field of reproductive medicine has seen significant progress in promoting good family planning, with one potential path being the critical role that IVF and PGT play in reducing the risk of genetic problem transmission. For people and couples struggling with genetic abnormalities, in vitro fertilization (IVF) offers a viable means of conception that greatly reduces the likelihood of passing these problems on to offspring.

Comprehending Genetic Disorders
Dr. Sneha Sathe, a fertility consultant at Nova IVF Fertility in Chembur, said in an interview with HT Lifestyle that genes, the basic building blocks of heredity, are crucial in defining our characteristics and general health. Each gene is inherited in two copies by each person, one from each parent. Deoxyribonucleic acid, or DNA, the building block of genes, carries the instructions needed to make proteins. Since they perform vital tasks for both cell upkeep and normal bodily function, proteins are very crucial to cells.

She disclosed that sometimes a mutation occurs in one or more genes, saying, “The mutation modifies the gene’s instructions for generating a protein, so the protein does not function correctly or is absent totally. Certain mutations have no obvious consequences, while others may affect our health and increase our chance of developing a genetic condition. These gene mutations may develop spontaneously over a person’s lifespan or can be inherited from one or both parents.

Genetic illnesses often fall into three primary groups, according to Dr. Sneha Sathe:

Single-gene disorders: These conditions arise when a single gene is impacted by a mutation. such as sickle cell disease.
Chromosome disorders: These conditions are caused by variations in the quantity or configuration of chromosomes. For instance, Down syndrome.
Multiple genes may be impacted by mutations in complex illnesses. These disorders are often exacerbated by environmental and lifestyle variables as well. For instance, colon cancer.
Genetic diseases’ prevalence in India
India has a high frequency of genetic abnormalities because of its vast population, rapid birth rate, and extensive practice of consanguineous marriages across different ethnicities. Dr. Sneha Sathe enumerated a few of the prevalent hereditary illnesses seen in India, including:

Reduced hemoglobin synthesis is the hallmark of the hereditary blood condition thalassemia. It happens as a result of changes or mutations in the genes that make hemoglobin. The two chains of hemoglobin are alpha and beta. Alpha thalassemia is caused by insufficient alpha, whereas beta-thalassemia is caused by insufficient beta. Thalassemia is inherited in an autosomal recessive manner. Each kid has a 25% chance of inheriting two faulty genes (thalassemia major), a 50% chance of receiving the thalassemia trait from both parents and a 25% chance of inheriting normal genes from both parents if both parents possess the trait. While people with thalassemia major often need blood transfusions, individuals with thalassemia trait may not exhibit any symptoms at all.

Sickle Cell Anaemia: Abnormal hemoglobin, which causes malformed red blood cells, is the hallmark of this genetic blood condition. Sickle cell anemia causes red blood cells to become hard and sickle-shaped, while normal red blood cells are round and flexible. The cells get lodged in blood arteries as a result of this shapeshift, which may cause discomfort, anemia, and other issues. There is an autosomal recessive pattern to the inheritance. A kid has a 25% probability of having sickle cell anemia if both parents possess the defective gene, a 50% chance of carrying one aberrant gene (being a carrier like the parents), and a 25% chance of inheriting normal genes from both parents.

Genetic disorders predominantly affecting the lungs and digestive tract are known as cystic fibrosis (CF). Due to a faulty gene, the body produces thick, sticky mucus that clogs pancreatic and other organ ducts and obstructs airways. This mucus accumulation affects other organs and causes recurrent lung infections, respiratory problems, and digestive problems. Given that CF is transmitted in an autosomal recessive manner, a child must have two defective copies of the gene—one from each parent—in order to become affected.

Duchenne muscular dystrophy (DMD): increasing muscle deterioration and weakening are hallmarks of this severe hereditary condition. It is brought on by a mutation in the gene that makes the protein dystrophin, which is essential for preserving muscle integrity. Boys are most affected by DMD, and symptoms often start to show in early infancy. Because the illness is inherited recessively via the X chromosome, the defective gene is found there. Because men have one X chromosome and one Y chromosome, they are more likely to acquire DMD if they inherit the defective gene on their X chromosome. With two X chromosomes, females are usually carriers of the defective gene; they may not exhibit symptoms, but they may still pass it on to their progeny.

The most prevalent genetic cause of hereditary intellectual impairment and autism spectrum disorder (ASD) is fragile X syndrome or FXS. A mutation in the FMR1 gene is the cause of it. Because this syndrome is inherited in an X-linked dominant manner, the condition may be brought on by a mutation in only one copy of the gene. Because they only have one X chromosome, men with the mutant gene are more seriously afflicted; females, on the other hand, may have fewer symptoms or be carriers of the illness.

Down syndrome: An additional copy of chromosome 21 causes Down syndrome, a genetic disease. Chromosome 21 normally contains two copies, however people with Down syndrome have a third copy, for a total of three copies. Physical and intellectual problems result from this extra genetic material interfering with normal development. One of the most prevalent chromosomal abnormalities in India, as well as around the world, is Down syndrome. i) Advanced maternal age: Having a child with Down syndrome rises with maternal age. This is one of the risk factors related to Down syndrome. A baby born to a woman over 35 years old is more likely to have Down syndrome.

ii) Previous Down syndrome kid: There is a modestly increased likelihood of a second Down syndrome child for parents who already have one.

iii) Genetic translocation: A parent may sometimes possess a rearranged copy of chromosome 21, which raises the possibility that their offspring would inherit an additional copy of this chromosome.

iv) Family History: Those who have the genetic translocation linked to Down syndrome or who have a family history of the disorder are more likely to have children with the disorder.

It’s crucial to remember that, despite the possibility being higher, most kids with Down syndrome are born to parents who do not have any recognized risk factors.

Preimplantation genetic testing (PGT) and in vitro fertilization (IVF): their roles in halting the spread of hereditary diseases
In order to identify undamaged embryos for uterine transfer, Dr. Sneha Sathe said, “IVF in conjunction with Preimplantation Genetic Testing (PGT) allows the screening of embryos for specific genetic abnormalities.” Ovarian stimulation, egg harvesting and fertilization in the IVF lab, and embryo culture to the blastocyst stage are the same first stages as in a typical IVF/ICSI cycle. A blastocyst biopsy is used in PGT, in which a sample of the trophectoderm—the outer layer of cells—is taken and examined for certain genetic abnormalities. This lowers the chance of the genetic problem spreading by enabling the selection and transfer of only unaffected embryos devoid of the known genetic defect.

She went on to explain that preimplantation genetic testing, or PGT, uses a variety of methods to check embryos for certain genetic disorders.

PGT-A (Aneuploidy): PGT-A examines embryos for aberrant chromosomal counts, with a focus on detecting aneuploidy (an erroneous chromosomal count). It assists in identifying embryos that have the appropriate number of chromosomes, preventing the transfer of embryos that have chromosomal abnormalities, such as those that are often linked to Down syndrome.

Screening for single-gene abnormalities or monogenic illnesses is done using PGT-M (Monogenic illnesses). It examines embryos for certain genetic variants connected to genetic disorders such as sickle cell anemia, DMD, cystic fibrosis, and so on. By selecting embryos devoid of the detected genetic abnormalities, this test lowers the likelihood that these disorders will be passed on to progeny.

PGT-SR, or structural rearrangements, is used when one or both parents have chromosomal rearrangements, such as inversions or translocations. By identifying and choosing embryos with healthy chromosomal configurations, this test lowers the risk of miscarriage or genetic abnormalities brought on by these rearrangements.

In order to choose and transfer embryos lacking a particular genetic defect, each PGT type has a distinct function in recognizing certain kinds of genetic abnormalities. This lowers the possibility that the genetic condition will be passed on to the kids.

Gametes from donors
“IVF techniques also offer additional options to further diminish the risk of passing on genetic disorders,” said Dr. Sneha Sathe. One possibility would be to use donor gametes if, for example, both parents had the same genetic mutation. By doing this, the possibility of the genetic condition being passed on to the progeny is eliminated via the use of donated eggs and/or sperm from unaffected donors. IVF has an effect on more than just the immediate marriage in terms of reducing the transfer of genetic diseases. By ending the cycle of hereditary illnesses within a family, it may have a favorable impact on subsequent generations.

“Although IVF and PGT offer promising avenues, they may not be foolproof solutions for all genetic disorders,” the speaker added. Couples may find these operations emotionally and financially taxing as well, so they should be carefully considered, counseled, and supported throughout the process. By enabling people and couples with genetic abnormalities to make educated decisions and drastically lower the chance of passing on genetic illnesses to their offspring, IVF with PGT has completely changed the landscape of reproductive medicine. These methods have the ability to help couples have healthy kids in spite of inherited genetic disorders as long as technology development continues.