India has a high prevalence of genetic disorders, which are a leading cause of death among infants and children in the poorest districts. However, recent advancements in reproductive medicine have opened up new avenues to prevent the transmission of these disorders. In this article, we will explore the common types of genetic disorders in India, their risk factors, and the role of IVF and PGT in mitigating them.

What are genetic disorders?

Genetic disorders are conditions that occur when a mutation affects one or more genes or chromosomes. Genes are the units of heredity that contain instructions for making proteins, which are essential for various functions in the body. Chromosomes are structures that carry genes and are present in pairs in every cell. Sometimes, due to various factors, genes or chromosomes can undergo changes that disrupt their normal functioning. This can lead to physical and mental abnormalities, diseases, and disabilities.

Common types of genetic disorders in India

According to Dr Sneha Sathe, Fertility Consultant at Nova IVF Fertility in Chembur, some of the common genetic disorders observed in India include:

Thalassemia: Thalassemia is a blood disorder that reduces the production of hemoglobin, the protein that carries oxygen in the blood. It occurs due to mutations in the genes that make hemoglobin. There are two types of thalassemia: alpha and beta, depending on which part of the hemoglobin molecule is affected. Thalassemia is inherited in an autosomal recessive pattern, meaning that both parents must carry the faulty gene for the child to have the condition. Thalassemia can cause anemia, fatigue, weakness, jaundice, and organ damage.
Sickle Cell Anemia: Sickle cell anemia is another blood disorder that affects the shape and function of red blood cells. It is caused by a mutation in the gene that makes hemoglobin, which causes the red blood cells to become rigid and sickle-shaped. This makes them prone to getting stuck in blood vessels, causing pain, inflammation, and reduced blood flow. Sickle cell anemia is also inherited in an autosomal recessive pattern, and can lead to complications such as infections, stroke, and organ failure.
Cystic Fibrosis: Cystic fibrosis is a disorder that affects the lungs and digestive system. It is caused by a mutation in the gene that makes a protein called CFTR, which regulates the movement of salt and water across cell membranes. This mutation causes the body to produce thick, sticky mucus that clogs the airways and ducts in the lungs, pancreas, and other organs. This leads to frequent lung infections, breathing difficulties, and digestive issues. Cystic fibrosis is inherited in an autosomal recessive pattern, and can affect other organs as well.
Duchenne Muscular Dystrophy (DMD): DMD is a severe disorder that causes progressive muscle degeneration and weakness. It is caused by a mutation in the gene that makes a protein called dystrophin, which is crucial for maintaining muscle integrity. DMD primarily affects boys, and symptoms usually appear in early childhood. The disorder follows an X-linked recessive inheritance pattern, meaning that the faulty gene is located on the X chromosome. Since males have one X chromosome and one Y chromosome, if they inherit the mutated gene on their X chromosome, they will likely develop DMD. Females, who have two X chromosomes, are typically carriers and may not show symptoms but can pass the faulty gene to their offspring.
Fragile X Syndrome (FXS): FXS is the most common genetic cause of inherited intellectual disability and autism spectrum disorder (ASD). It results from a mutation in the FMR1 gene, which makes a protein that is involved in brain development and function. This mutation causes the gene to be turned off or silenced, leading to reduced or absent production of the protein. FXS is inherited in an X-linked dominant pattern, meaning that a mutation in one copy of the gene can cause the disorder. Males with the mutated gene are more severely affected because they have only one X chromosome, while females, who have two X chromosomes, may have milder symptoms or be carriers of the condition.
Down Syndrome: Down syndrome is a chromosomal disorder that occurs when a person has an extra copy of chromosome 21. Normally, a person has two copies of each chromosome, but individuals with Down syndrome have three copies of chromosome 21. This additional genetic material disrupts the normal course of development, leading to physical and intellectual disabilities. Down syndrome is one of the most common chromosomal disorders observed in India, as it is globally. The risk factors associated with Down syndrome include advanced maternal age, previous child with Down syndrome, genetic translocation, and family history.

Role of IVF and PGT in preventing transmission of genetic disorders

IVF, or in vitro fertilization, is a technique that involves fertilizing an egg with a sperm outside the body, and then transferring the resulting embryo into the uterus. PGT, or preimplantation genetic testing, is a technique that involves screening the embryos for specific genetic abnormalities, before transferring them into the uterus. These techniques can help couples with genetic disorders to conceive while significantly reducing the chance of passing these disorders to their children.

Dr Sneha Sathe explained, “IVF, combined with PGT, allows the screening of embryos for specific genetic abnormalities, enabling the selection of unaffected embryos for transfer into the uterus. The initial steps are the same as those of a standard IVF/ICSI cycle- ovarian stimulation, egg retrieval and fertilization in the IVF laboratory, and embryo culture to the blastocyst stage. For PGT, blastocyst biopsy is carried out, where some cells are removed from the outer layer of cells of the developing embryo (trophectoderm) and tested for specific genetic abnormalities. This allows the selection and transfer of only unaffected embryos that do not carry the identified genetic condition, reducing the risk of transmission of the genetic disorder.”

There are different types of PGT, depending on the type of genetic abnormality being tested for. PGT-A tests for aneuploidy, or abnormal chromosome numbers, such as those associated with Down syndrome. PGT-M tests for single-gene disorders, or monogenic diseases, such as cystic fibrosis, sickle cell anemia, or DMD. PGT-SR tests for structural rearrangements, or changes in the shape of chromosomes, such as translocations or inversions.

IVF and PGT can also offer additional options to further diminish the risk of passing on genetic disorders. For instance, in cases where both parents carry the same genetic mutation, donor gamete/s could be considered as an option. This involves using donated eggs and/or sperm from unaffected donors, thereby eliminating the risk of passing on the genetic disorder to the offspring.

Dr Sneha Sathe concluded, “It is important to acknowledge that while IVF and PGT offer promising avenues, they may not be foolproof solutions for all genetic disorders. Additionally, these procedures can be emotionally and financially challenging for couples, and hence require careful consideration, counseling, and support throughout the process. IVF with PGT has transformed the landscape of reproductive medicine by empowering individuals and couples with genetic disorders to make informed choices and significantly reduce the risk of passing on genetic disorders to their children. With continued technological advancements, these approaches continue to hold the potential to assist couples in establishing healthy families despite inherited genetic conditions.”