Overview

Definition of autosomal dominant disorders

Autosomal dominant disorder is a genetic disease which occurs when one of the autosomal genes is mutated. The disease is called dominant because a single copy of the gene inherited by the child, from one infected parent, is enough to cause the disorder. There is a 50% chance that a person will have a dominant disorder if one of the parents has the mutant gene. It can also affect a person with no prior family history of mutated genes.¹

Importance of understanding genetic inheritance

The knowledge of basic genetic inheritance is important for everyone, it gives an idea of how a disorder or condition is passed through generations in a family and it also helps to identify potential risks. A person has two copies of the gene inherited one from each parent. A change in genes can lead to genetic disease, while a slight change does not affect the person.²

Overview of the outline 

The following article includes all aspects of the autosomal dominant disease, its inheritance pattern, diagnosis, genetic screening, treatment management, and general counseling. Some examples of autosomal dominant disorders are briefly described in the article. 

Genetic basics

Explanation of chromosomes and genes

To understand the article better, understanding the following terms will be helpful. 

Chromosomes are genetic molecules of an organism. All organisms have different sets of chromosomes. The total number of chromosomes in humans is 46 or 23 pairs of chromosomes. Each set of chromosomes contains one copy from the mother and one from the father. Out of the 23 pairs only one pair called a sex chromosome determines the sex of the organism while 22 pairs are called autosomes, which help in other functions of the body.³ Mutations in chromosomes can lead to genetic disorders 

Gene is a small unit of heredity located on the chromosome. Genes contain the genetic information that passes through generations. The human genome contains 25000 genes. 

 Autosomes vs. sex chromosomes

44 chromosomes are called autosomes, they control all the characteristics of organisms except sex-linked ones. Any slight change in the autosomal chromosomes, that is addition or deletion of chromosomes, can result in serious disability and disorder.

Sex chromosomes are the 23rd pair of chromosomes containing X & Y that determine the sex of an organism, females contain XX and males contain XY chromosomes.⁵

Role of dominant and recessive alleles

An organism inherits two versions of each gene from both parents. In dominant disorder, only one copy of the defective gene is enough to express the damaged trait in the child. That means there is a 50% chance of acquiring the disease.⁶ In a recessive disorder, the gene inherited from each parent needs to have the defective gene to express the trait in offspring. If only one gene is damaged, there won't be a problem.⁷

The changes can range from a change in hair colour or eye to serious health conditions. 

Inheritance pattern

Knowledge of basic hereditary law is important to understand how a trait is passed through generations. Disorder due to mutation in a single gene shows a simple inheritance pattern.

As mentioned above, a person acquires a copy of the gene from each parent, in some cases one of the genes inherited is a mutant gene. In the case of autosomal dominant disorder. If any parent has a mutant gene located on the autosomal chromosome, the offspring may inherit the disease. This disorder is passed down through generations and can equally affect males or females. However, the symptoms may not be expressed similarly in every person infected, even in the family.⁸

Examples of autosomal dominant disorders

Huntington's disease (HD)

A neurodegenerative genetic disease that causes brain nerve cells to degenerate. This disorder attacks the part of the brain responsible for voluntary movements and other brain areas. An individual affected by HD suffers from uncontrollable movements and abnormal body posture.

The disease is passed from parent to offspring through a mutant gene located on autosomal chromosome 4 which is responsible for protein huntingtin. The mutation causes abnormal repetition of cytosine, adenosine, and guanine nucleotides that form DNA. The symptoms are divided into physical changes, behavioural changes, and emotional changes.

The symptoms generally appear in adults to middle age groups but can also be rarely seen in children. The physical symptoms include speech disability, difficulty in eating, speaking, walking, and difficulty in balance and movements. The behavioural changes disappear as the disease grows, but can be a lifetime change in some people, they include mood swings, irritation, anger, and depression. Some other symptoms are insomnia, inactivity, weight loss, fatigue, unusual eye movements, and difficulty in thinking and understanding.⁹

Marfan syndrome

A common disease that affects people of all races and genders. The frequency of Marfan syndrome is 1 in 5000, and out of 4 cases of the disease 3 are inherited. It occurs due to a mutation in a gene that codes for fibrillin 1 protein, responsible for making connective tissue and normal growth and development of the body. The mutation causes abnormality in the formation of protein resulting in changes in the strength and growth of tissues, including blood vessels, heart, skin, and tendons. The protein also happens to affect the performance of another protein TGG-beta which has roles in normal cell functioning throughout the body

Symptoms of Marfan syndrome include: (The symptoms can vary from mild and few to serious)

• Overgrowth of arms, legs, fingers, toes, chest walls
• Change in the curvature of the spine
• Flat feet
• Headaches
• Faster heartbeat, fluttering in heart
• Loose joints
• Back pain and numbness in legs
• Shortness of breath
• Changes in vision, cataracts, blurry visions
• Stretch marks on the skin¹⁰

Familial hypercholesterolemia (FH)

A genetic disorder characterized by a high level of low-density lipoprotein (LDL) in the bloodstream. LDL in general terms is known as bad cholesterol. The normal level of LDL in the body is 100mg/dl, but in FH's case, the level increases to 400 mg/dl. The LDL cholesterol blocks the artery that prevents normal blood flow leading to heart attack and other heart diseases.

The level of LDL in the people inheriting the disease starts increasing since birth, therefore early treatment can decrease the risk up to 80%. The mutation in the gene of chromosome 19, responsible for developing proteins that flush out LDL from blood, doesn't act properly. Symptoms are generally hidden until someone develops a cardiovascular disease.

Some of the symptoms are angina, heart attack, stroke, calf cramps, bumps or lumps around joints of body, swelling or pain Achilles tendon, yellowness around the eyes or a white-gray curve around the cornea.¹²

Diagnosis and management

Genetic testing and counseling

Genetic test is a technique used in diagnosis. They are of different kinds and can be used for different purposes. The genetic test is of three types:

• Cytogenetic testing: it is an examination of the whole chromosome to check the abnormal chromosome or gene
• Biochemical tests: examine different types of proteins present in the body to check any dysfunction in protein synthesis
• Molecular testing: small DNA mutations are examined using molecular tests by using a small amount of sample

Uses of genetic testing: (Genetic tests can be used according to your needs)

• Newborn screening
• Carrier testing Prenatal diagnostic testing
• Predictive or predisposition testing

Genetic counseling

Genetic counsellors are healthcare professionals who educate and provide information about genetic diseases and risks to affected families. They help families identify possible risks of having a genetic disorder by collecting sufficient information about the disease, family history,and inheritance patterns, and calculating any chance of recurrence of the disease.

If a person has a genetic disease, they provide the patient with a disease management plan, risks, and benefits of testing, and reduce stress and anxiety of families.²

Treatment options

Early diagnosis can help in minimizing the risks and symptoms of genetic disorders to a significant extent. Some genetic disorders can be controlled using particular medications, while many depend on gene therapies. Medications targeting symptoms can be used in the management of disease. Potential gene therapies are used in targeting different types of genetic diseases. Further research is needed to treat genetic disorders by using various techniques and management systems.

Implication for families

An individual suffering from a genetic disease suffers from physical difficulties as well as emotional and social distress. It also impacts the person's families. Therefore, sufficient knowledge of genetic diseases of the individual and their family is important to decrease their sadness and stress. Counselling by professional genetic counsellors is very impactful in helping the family of affected people.

Summary

The autosomal dominant disorder is an inherited genetic disease that can impact people of any group and gender. Most of the dominant disorders are inherited by infected parents but in some cases, it can be spontaneous in people. In dominant genetic disease, if one of the parents is a carrier or has the mutation gene, the dysfunctional gene is in their child and it goes down in generations.

Gene defects in any autosomal chromosome number can lead to different types of autosomal dominant disease. Different disorders have different symptoms and target particular organs of the body. The diagnosis of genetic diseases is conducted through genetic testing, which examines the person's genes or chromosomes.

Families with a history of genetic disorders should undergo genetic testing to prevent the severity of these conditions. There are different kinds of genetic tests that examine the risk of disease. People considering starting a family with a genetic history should go for carrier testing, to check if the foetus suffers any gene defect the tests conducted are prenatal tests. The treatment of genetic disorders involves symptom management and gene therapy.

Genetic disease can impact a person's as well as the family members' physical, mental, and social well-being. Therefore, genetic counseling happens to be an important session for the person and their family for the right disease management and mental health. Further research and studies need to be done in the files of treatment of genetic disorders.