Genetic disorders in India: Common types, risk factors, preventing transmission

Understanding Genetic Disorders

In an interview with HT Lifestyle, Dr Sneha Sathe, Fertility Consultant at Nova IVF Fertility in Chembur, shared, “Genes, the fundamental units of heredity, play a pivotal role in determining our traits and overall health. Every individual has two copies of each gene, one inherited from each parent. Genes are made of DNA (deoxyribonucleic acid) that contains instructions for making proteins. Proteins are incredibly important in cells as they carry out essential functions necessary for cell maintenance and overall body function.”

Revealing that sometimes there is a mutation (a change) in a gene or genes, she said, “The mutation changes the gene's instructions for making a protein, so the protein does not work properly or is missing entirely. While some mutations don't cause any visible effects or problems, others can impact our health and raise the risk of having a genetic disorder. These gene mutations can be inherited from one or both parents or can also occur spontaneously during an individual's lifetime.”

According to Dr Sneha Sathe, genetic disorders typically fall into three main categories -

• Single-gene disorders: These disorders occur when a mutation impacts just one gene. Eg. sickle cell anemia.
• Chromosomal disorders: These disorders result from a change in the number or structure of chromosomes. Eg. Down syndrome.
• Complex disorders: In these disorders, mutations might affect multiple genes. Additionally, lifestyle and environmental factors often contribute to these conditions. Eg. colon cancer.

Prevalence of genetic disorders in India

Due to India's large population, high birth rate, and widespread practice of consanguineous marriages within various communities, there is a high prevalence of genetic disorders in the country. Dr Sneha Sathe listed some of the common genetic disorders observed in India include -

• Thalassemia: Thalassemia is an inherited blood disorder characterised by reduced production of hemoglobin. It occurs due to mutations or alterations in the genes responsible for producing hemoglobin. Haemoglobin comprises alpha and beta chains. A shortage of alpha causes alpha thalassemia, and low beta leads to beta-thalassemia. The inheritance of thalassemia follows an autosomal recessive pattern. If both parents carry the thalassemia trait, each child has a 25% chance of inheriting two abnormal genes (thalassemia major), a 50% chance of being a carrier (thalassemia trait) like the parents, and a 25% chance of inheriting normal genes from both parents. Those with thalassemia trait may show no symptoms, while those with thalassemia major often require frequent blood transfusions.
• Sickle Cell Anaemia: Sickle cell anemia is an inherited blood disorder characterized by abnormal hemoglobin, resulting in misshapen red blood cells. Normal red blood cells are round and flexible, but in sickle cell anemia, they become rigid and sickle-shaped. This change in shape causes the cells to get stuck in blood vessels, leading to pain, anemia, and various complications. The inheritance follows an autosomal recessive pattern. If both parents carry the abnormal gene, there's a 25% chance that the child will have sickle cell anemia, a 50% chance the child will carry one abnormal gene (being a carrier like the parents), and a 25% chance the child will inherit normal genes from both parents.
• Cystic Fibrosis: Cystic fibrosis (CF) is a genetic disorder primarily affecting the lungs and digestive system. It results from a defective gene, causing the body to produce thick, sticky mucus that obstructs airways and blocks ducts in the pancreas and other organs. This build-up of mucus leads to frequent lung infections, breathing difficulties, and digestive issues, and can affect other organs. CF is inherited in an autosomal recessive pattern, meaning a child must inherit two abnormal copies of the gene (one from each parent) to develop the condition.
• Duchenne Muscular Dystrophy (DMD): DMD is a severe genetic disorder characterised by progressive muscle degeneration and weakness. It is caused by a mutation in the gene responsible for producing a protein called dystrophin, 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 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, with 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. This syndrome is inherited in an X-linked dominant pattern, meaning 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.
• Downs Syndrome: Downs syndrome is a genetic disorder caused by the presence of an extra copy of chromosome 21. Typically, a person has two copies of chromosome 21, but individuals with Down syndrome have a third, resulting in a total of three copies. 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 -

i) Advanced maternal age: The risk of having a child with Down syndrome increases with maternal age. Women over 35 years old have a higher likelihood of giving birth to a baby with Down syndrome.

ii) Previous child with Down syndrome: Parents who have one child with Down syndrome have a slightly higher chance of having another child with the same condition.

iii) Genetic translocation: In some cases, a parent can carry a rearranged chromosome 21 that increases the likelihood of passing on an extra copy of this chromosome to their child.

iv) Family History: Individuals with a family history of Down syndrome or carriers of the genetic translocation associated with this condition have an increased risk of having a child with Downs syndrome.

It's important to note that while these factors may increase the likelihood, most babies born with Down syndrome are born to parents with no known risk factors.

Role of IVF and Preimplantation Genetic Testing (PGT) in preventing transmission of genetic disorders

Dr Sneha Sathe explained, “IVF, combined with Preimplantation Genetic Testing (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.”

Stating that Preimplantation Genetic Testing (PGT) comprises various techniques to screen embryos for specific genetic conditions, she elaborated -

• PGT-A (Aneuploidy): PGT-A assesses embryos for abnormal chromosome numbers, specifically checking for aneuploidy (an incorrect number of chromosomes). It helps identify embryos with the correct number of chromosomes, allowing us to avoid transferring embryos with chromosomal abnormalities, such as those commonly associated with Down syndrome.
• PGT-M (Monogenic Diseases): PGT-M is used to screen for single-gene disorders or monogenic diseases. It tests embryos for specific genetic mutations linked to hereditary conditions like cystic fibrosis, sickle cell anemia, DMD etc. This test enables the selection of embryos without the identified genetic mutations, reducing the risk of passing these conditions to offspring.
• PGT-SR (Structural Rearrangements): PGT-SR is employed when one or both parents carry structural rearrangements in their chromosomes, such as translocations or inversions. This test detects and selects embryos with normal chromosomal structures, decreasing the chance of miscarriage or genetic disorders associated with these rearrangements.

Each PGT type serves a specific purpose in identifying specific types of genetic abnormalities, allowing for the selection and transfer of embryos without the specific genetic abnormality, thereby reducing the likelihood of passing on the genetic disorder to the offspring.

Donor gametes

Dr Sneha Sathe said, “IVF techniques 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. The impact of IVF on preventing the transmission of genetic disorders extends beyond just the immediate couple. It can positively influence future generations by breaking the cycle of inherited diseases within a family.”

She 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.”