Genetic Disorders

Genetic disorders may be classified as follows:

• X-linked disorders occur when genes on the X chromosome (one of the sex chromosomes) are faulty.
• Autosomal dominant disorders occur when only one copy of a gene (from either parent) is faulty.
• Autosomal recessive disorders occur when both copies of a gene (from each parent) are faulty.
• Mitochondrial disorders occur due to mutations in the mitochondria, which are specialised energy-producing structures inside cells.
• Chromosomal disorders are caused by alterations in the chromosomal structure or number.
• Multifactorial disorders develop due to genetic and environmental factors.

Each genetic disorder has its own set of features and inheritance patterns, which greatly affect how these conditions are managed. The treatment of these disorders can therefore vary greatly. Below are some genetic disorders along with their clinical manifestations:

• Cystic fibrosis (autosomal recessive) is a genetic condition that causes thick, sticky mucous to build up in the lungs and digestive system. This leads to breathing difficulties, repeated chest infections, and problems digesting food. It is usually detected in infancy or early childhood.
• Haemophilia (X-linked) affects the blood’s ability to clot, leading to frequent or prolonged bleeding, easy bruising, and sometimes joint pain or swelling from internal bleeding. It is typically detected in infancy or early childhood.
• Mitochondrial disorders (mitochondrial inheritance) interfere with the body’s ability to produce energy. This may cause muscle weakness, tiredness, poor growth with vision or hearing problems, and sometimes seizures. They can be detected at any age, from infancy to adulthood depending on the severity.
• Down’s syndrome (chromosomal disorder) is characterised by an extra copy of chromosome 21. It is usually detected at birth or in some cases, during pregnancy, via screening tests. Features may include distinctive facial characteristics, developmental delays, learning difficulties, and in some cases heart or digestive problems.
• Hereditary cancers include certain breast, ovarian, and colorectal cancers linked to inherited mutations (e.g., those in the BRCA1/2 genes).
• Hereditary cardiac conditions include hypertrophic cardiomyopathy and long QT syndrome, which may cause arrhythmias or sudden cardiac events.
• Chromosomal abnormalities may cause birth defects, intellectual disabilities, or reproductive problems.
• Inherited metabolic disorders such as phenylketonuria, maple syrup urine disease, interfere with the body’s ability to process certain proteins, fats, and carbohydrates.
• Single-gene disorders are conditions that arise due to mutations in one gene. Depending on the faulty gene inherited, they may be X-linked or autosomal dominant or recessive. Single-gene disorders include:
  • Thalassaemia: Characterised by anaemia occurring due to abnormal haemoglobin production.
  • Muscular dystrophy: Characterised by progressive muscle weakness.
  • Huntington’s disease (autosomal dominant): A disease affecting the brain and nervous system, characterised by uncontrolled movements, memory issues, mood changes, and difficulty with speech or swallowing.
  • Sickle cell anaemia: Characterised by the formation of abnormal red blood cells, leading to anaemia, episodes of severe pain, and organ complications.
• Birth defects with a genetic component include neural tube defects, cleft lip/palate.

Genetic disorders can arise from several factors:

• Changes or mutations in a single gene.
• Complex interactions between multiple genes and environmental factors.
• Environmental exposures, such as toxins, radiation, or certain medications, can trigger or worsen genetic conditions.

Inherited conditions are often diagnosed via the following methods:

• A medical assessment involving a comprehensive review of the family’s medical history and physical examination.
• Genetic testing is recommended based on the case presentation.

These tests might be performed during pregnancy, after childbirth (neonatal and paediatric testing), or during adulthood, depending on the suspected disorder and individual circumstances.

Most genetic disorders have no permanent cure. Treatments mainly focus on symptom management, prevention of complications, and enhancing the quality of life. Because these conditions present with diverse manifestations, their management requires a multidisciplinary approach that includes: 

• Medical therapies such as clotting factor replacement in haemophilia or enzyme replacement therapy in certain metabolic disorders.
• Lifestyle modification, for example, a low phenylalanine diet in phenylketonuria.
• Surgical interventions, such as cleft lip repair or corrective surgery for congenital heart conditions.
• Genetic counselling plays an important role as both a supportive and preventive strategy. It helps individuals and families cope with the emotional, social, and practical challenges of living with a genetic condition.

You should consult a doctor or a genetic specialist if: 

• There is a family history of a known genetic disorder (e.g., thalassaemia, haemophilia, Huntington’s disease).
• Your child shows unexplained developmental delays, learning difficulties, or intellectual disabilities.
• An adult shows unexplained cognitive decline (memory loss or reduced ability to perform daily activities)
• There are recurrent or unusual health problems, such as frequent chest infections (as in the case of cystic fibrosis) or unexplained muscle weakness (muscular dystrophy).
• Physical symptoms, such as cleft lip or cleft palate, are present in a newborn child.
• Congenital birth defects diagnosed at birth or shortly after.
• You are planning a pregnancy and want to understand your risk of passing on a genetic condition (e.g., if you are a known carrier of sickle cell disease).
• Prenatal screening tests suggest possible chromosomal abnormalities such as Down’s syndrome.
• Sudden health issues arise, suggesting inherited cardiac or metabolic conditions.

While genetic conditions cannot be fully prevented, the following steps can help reduce risk, enable early detection, and support informed decision making: 

• Genetic counselling helps patients with a family history of genetic disorders understand their risks before planning a pregnancy.
• Carrier screening helps ascertain whether prospective parents harbour specific genetic mutations, such as thalassaemia, cystic fibrosis, or sickle-cell disease.
• Prenatal testing, including chorionic villus sampling (CVS) or amniocentesis, can help detect chromosomal abnormalities (e.g., Down’s syndrome) during pregnancy.
• Preimplantation genetic testing (PGT) is used for couples undergoing in vitro fertilisation (IVF), where embryos are screened for certain genetic disorders before implantation.
• Healthy lifestyle choices, such as avoiding alcohol and certain medications during pregnancy can help reduce the risks of triggering or worsening some genetic conditions.

Consult a genetic specialist or genetic counsellor for evaluation, risk assessment, and guidance on inherited conditions.