Gene Disorders

Disorders that result from inheriting an altered gene or genes

  • Always present at birth but effects may not become apparent until later
  • Gender as a risk factor depends on the type
  • Lifestyle is not a significant factor for most disorders

Genes provide instructions to the cells to make enzymes and other proteins and molecules that the body needs to grow and function. A defective gene may have mild, moderate, or potentially fatal consequences or no effect at all, depending on the role of the protein or molecule for which the gene codes. The development of many common disorders, such as diabetes mellitus and asthma, is linked with genetic factors but is also influenced by environment and lifestyle.

Several thousand disorders are the result of alterations in single genes, but the majority of these conditions are extremely rare. Some of the most common single gene disorders include haemophilia (see Haemophilia and Christmas disease), cystic fibrosis, sickle-cell disease, and thalassaemia. About 1 in 100 babies is born with a disorder that is caused by an alteration in one or both copies of a single gene.

Some communities have high frequencies of abnormal genes for certain disorders. For example, the gene that produces Tay–Sachs disease is more common among Ashkenazi Jews, and the gene for thalassaemia is more common in people from Mediterranean countries and Asia.

Some gene disorders are obvious soon after birth or in the first few months of life. Symptoms of other disorders caused by a single altered gene, such as Huntington’s disease, do not appear until adult life.

What are the causes?

In most gene disorders, an individual has an altered gene in all body cells from conception. There are two possible reasons for the presence of the altered gene. First, and most commonly, the altered gene may have been passed on from parent to child. Second, the gene may have become changed (mutated) during meiosis, the process of division by which eggs and sperm form. This is one reason why somebody with a genetic condition may be the only person in the family who is affected.

What are the types?

Genes occur in pairs; one of each pair is inherited from the mother, the other from the father. Genes are located on the 22 pairs of chromosomes known as autosomes and also on the X and Y sex chromosomes. Single gene disorders are classified by their pattern of inheritance: autosomal dominant, autosomal recessive, or X-linked. In addition, many common disorders are the result of an interaction between genes, the environment, and lifestyle. These are known as multifactorial (or common complex) disorders.

Autosomal dominant disorders

A person with an autosomal dominant condition has one gene of a particular pair with an alteration; the other gene of the pair is the usual form. The effect of the altered gene (the dominant trait) overrides the effect of the usual gene (the recessive trait). Each child of a person with an autosomal dominant disorder has a 1 in 2 chance of inheriting the altered gene and developing the disorder. Familial hypercholesterolaemia is one of the most common conditions to follow this pattern of inheritance (see Inherited hyperlipidaemias). In this disorder, high levels of blood cholesterol lead to an increased risk of early coronary artery disease. About 1 in 500 people of European descent has this gene and is affected by the disorder.

Autosomal dominant disorder

In this example, one of the parents has the altered gene and the other parent is unaffected. Each child has a 1 in 2 chance of inheriting the altered gene and therefore developing the disorder.

Autosomal recessive disorders

A person with an autosomal recessive condition has two copies of an altered gene, one from each parent. If a person has one copy of the altered gene but the second copy is normal, the person is a carrier. A carrier does not develop the disease but may pass the altered gene on to his or her children. Most autosomal recessive disorders are rare. Cystic fibrosis, a disease that affects certain glands, is the most common autosomal recessive disorder in white Europeans. In the UK population, about 1 in 25 people is a carrier of the disease. The chance of two carriers meeting is therefore about 1 in 625. If two carriers have a child, there is a 1 in 4 probability of the child inheriting two altered genes and so overall, cystic fibrosis affects about 1 in 2,500 people. The most common autosomal recessive disorder among black people is sickle-cell disease: 1 in 10 people is a carrier and about 1 in 400 has the disorder.

Autosomal recessive inheritance

In this example, both parents carry the altered gene but do not have the disease. Their children may be unaffected (1 in 4 chance), may be carriers of the altered gene (1 in 2), or may have the disease (1 in 4).

X-linked recessive disorders

In a disorder of this type, such as haemophilia, the altered gene is on the X chromosome. Women who have one altered gene are usually unaffected carriers because the usual gene on the second X chromosome counterbalances the effects of the altered gene. However, they may pass on the altered gene to their children. Since each child inherits one X chromosome from the mother, each child of a carrier has a 1 in 2 chance of inheriting the altered gene. If a boy inherits the altered gene, he will develop the disorder because he has a Y chromosome and not a second X chromosome. Girls are carriers because the normal gene on the X chromosome inherited from their father masks the effects of the altered gene. A man with an X-linked autosomal recessive condition will pass on the altered gene to all his daughters (who will be carriers) but not to his sons.

X-linked recessive inheritance

In this example, a mother carries the altered gene on the X chromosome but is unaffected. Each son has a 1 in 2 chance of inheriting the disease; each daughter has a 1 in 2 chance of being a carrier but is unlikely to have symptoms of the disease.

Multifactorial disorders

There are many common disorders, including asthma, that run in families but for which no single gene appears to be responsible. In these disorders, it is likely that several different genes interact with lifestyle and environmental factors to cause the disease. Certain disorders are known to be associated with a group of proteins called HLAs, which form part of the body’s immune system and determine a person’s tissue type. HLAs are inherited, and each individual has a unique combination of them. In some people, particular HLAs increase susceptibility to certain disorders, such as ankylosing spondylitis and systemic lupus erythematosus.

What might be done?

The underlying cause of single gene disorders cannot be treated. Gene therapy, in which a normal copy of a gene is inserted into cells, holds promise for some conditions but is technically very challenging. However, the symptoms of many gene disorders can be treated successfully. For example, people who have haemophilia are unable to produce a protein involved in blood clotting, and are treated with injections of the missing protein. Similarly, improved treatment for people with cystic fibrosis, has increased life expectancy. However, some disorders due to a single gene, such as Huntington’s disease, are not easily treated and have severe consequences.

Can they be prevented?

People who have a blood relative with an inherited disorder may be able to have a genetic test to determine whether they have the altered gene, but tests are available only for certain disorders, such as cystic fibrosis and sickle-cell disease, in which the altered gene has been identified. A couple with a family history of a gene disorder may opt for genetic counselling before conceiving or have antenatal genetic tests for fetal abnormalities. Screening may be offered to whole communities in which there is a high incidence of a faulty gene. For example, Ashkenazi Jews may be screened for Tay–Sachs disease.

Test: Genetic Counselling

From the 2010 revision of the Complete Home Medical Guide © Dorling Kindersley Limited.

The subjects, conditions and treatments covered in this encyclopaedia are for information only and may not be covered by your insurance product should you make a claim.

Back to top