Autosomal dominant disease

Related Terms

Allele, autosome, chromosome, dominant inheritance, familial adenomatous polyposis, gene therapy, genetic counseling, genetic testing, HTT gene, huntingtin gene, Huntington's disease, Marfan syndrome, neurofibromatosis-1, penetrance, prenatal testing.

Background

Chromosomes contain the genetic material found in all cells. Each human cell has 23 pairs of chromosomes, including one pair of sex chromosomes and 22 pairs of non-sex chromosomes called autosomes. The sex chromosomes include the X chromosome and the Y chromosome. Females have two X chromosomes, while males have one X chromosome and one Y chromosome.
Genes are found within the chromosomes of all organisms. An individual's genes are present in a large molecule called deoxyribonucleic acid (DNA). DNA is made up of different combinations of four nucleic acids (adenine, thymine, cytosine, guanine), which are arranged in different lengths. The sequence of these molecules provides the "code," or instructions, for construction of each of the proteins involved in the development, growth, and function of all the cells in the body. An autosomal dominant disorder may occur when the nucleic acid sequences that make up individual genes are incorrect, or mutated. When a gene is mutated, the protein that it codes for may stop functioning or may no longer function properly, which can cause a disorder or disease.
Autosomes are the non-sex chromosomes. Individuals have two copies or alleles of the 22 autosomes (one copy inherited from each parent). Each parent can only pass one allele, or version of their genes, to their child. Which copy is passed down is determined by chance.
Autosomal dominant disorders are caused by a mutation in an autosomal gene. In order to have an autosomal dominant disorder, only one copy of the gene (inherited from either parent) needs to contain a disease-causing mutation. This is different from autosomal recessive disorders, in which a person needs to inherit two copies of a mutant gene to be affected by the disorder. Because males and females share the same autosomal chromosomes, they are affected equally by autosomal dominant disorders.
Huntington's disease, Marfan syndrome, familial adenomatous polyposis, and neurofibromatosis-1 are examples of autosomal dominant disorders. Huntington's disease is a neurological disorder characterized by abnormal body movements and a lack of coordination. Marfan syndrome is a connective tissue disorder characterized by abnormally long arms, legs, and fingers and a predisposition to cardiovascular problems. Familiar adenomatous polyposis is characterized by cancer of the large intestine and rectum. Neurofibromatosis-1 is characterized by tumors of the nervous tissue.

Signs and symptoms

Each autosomal dominant disease has different symptoms, depending on the gene that is mutated. In some cases, people who have an autosomal dominant disease do not exhibit symptoms until adulthood. Symptoms may also be triggered by certain events, such as illness or exposure to certain environmental toxins.
Patients with Huntington's disease have abnormal body movements and a lack of coordination. Symptoms of Marfan syndrome include abnormally long arms, legs, and fingers and cardiovascular problems. Symptoms of familial adenomatous polyposis include gastrointestinal problems. Symptoms of neurofibromatosis-1 may include mental disabilities and tumors near the skin.

Diagnosis

Genetic testing: Currently, genetic tests are available to diagnose more than 1,000 different types of genetic disorders. Genetic testing may be used to diagnose children or adults with an autosomal dominant disorder. In addition, genetic tests can diagnose the presence of an autosomal dominant disorder in a developing fetus.
Genetic tests are typically performed if there is a family history of a disorder, if the individual belongs to a certain ethnic or cultural group in which the disorder is common, or when patients display symptoms of specific genetic disorders. In some cases, genetic testing is done to confirm a diagnosis of an autosomal dominant disease that was based on symptoms alone. Some autosomal dominant disorders do not develop until later in life, in which case individuals may pass the disease to their children before symptoms appear and the disease is detected.
A genetic test will either look at the products of a specific gene or test if the gene itself is faulty. A sample of an individual's blood, saliva, or tissue is taken and sent to a lab to look for the defective gene. The results of the test may take anywhere from a few days to a few weeks to be available. Researchers need to identify a causative mutation in a specific gene to be able to do genetic testing and diagnose a disease. Therefore, genetic tests do not yet exist for all genes and genetic disorders. Ongoing research will increase the number of autosomal dominant disorders that can be diagnosed using genetic testing.
Newborn screening: Newborn screening is the practice of testing every newborn for certain harmful or potentially fatal disorders that are not otherwise apparent at birth. Requirements for newborn screening depend on the state in which the child is born. Some states screen for 10 different disorders while others screen for more than 30 possible disorders. These simple tests can determine whether newborns have certain conditions that could eventually cause health problems. Even though these conditions are considered rare and most babies are given a clean bill of health, early diagnosis and proper treatment can make the difference between lifelong impairment and healthy development. For example, newborn screening is used to detect a form of hearing impairment that is inherited in an autosomal dominant manner. Early detection allows for early treatment, which decreases hearing loss and allows those affected to lead relatively normal lives.
Genetic counseling: Before and after genetic testing, it is recommended that people meet with genetic counselors. A genetic counselor can explain the different types of genetic tests, including their potential risks and benefits, and can help individuals decide whether genetic testing is appropriate. These counselors can also help patients understand and interpret test results, which helps individuals understand the risks and limits of genetic testing.
Prenatal testing:
General: Prenatal testing may be used to check if a growing fetus has a mutation in a gene that is associated with a disease. Prenatal screening tests may be able to detect if a fetus is at increased risk of getting a disease or is a carrier of a genetic mutation. Prenatal diagnostic tests may be able to diagnose a developing fetus with a specific genetic disorder. Although rare, there are serious risks associated with prenatal tests. Patients should discuss the potential health benefits and risks associated with these procedures before making any medical decisions.
Ultrasound: An ultrasound may be used to see if the fetus has any physical abnormalities associated with an autosomal dominant disorder. An ultrasound uses high-frequency sound waves to make a picture of the fetus. Ultrasounds are generally regarded as safe, but they may not be as sensitive as other tests. An ultrasound is generally the least reliable prenatal test because it does not look at the actual DNA or chromosomes of the fetus and can only detect physical signs of the disorder. Ultrasound results may appear normal even if the fetus has a disorder.
Amniocentesis: During amniocentesis, a long, thin needle is inserted through the abdominal wall into the uterus and a small amount of amniotic fluid is removed from the sac surrounding the fetus. The fluid is then analyzed for a mutated gene. This test is performed after 15 weeks of gestation. However, amniocentesis is associated with a risk of miscarriage. Some experts estimate that the risk of miscarriage is between one in 200 and one in 400 patients. Risk of miscarriage is highest when the procedure is done early in pregnancy, before the two layers of fetal membranes have sealed. A woman's particular risk depends in large part on the skill and experience of the doctor performing the procedure. Some patients may experience minor complications, such as cramping, leaking fluid, or irritation where the needle was inserted.
Chorionic villus sampling (CVS): During chorionic villus sampling (CVS), a small piece of tissue called the chorionic villus is removed from the placenta during early pregnancy. Depending on where the placenta is located, CVS can be performed through the cervix or through the abdomen. The tissue sample is then analyzed for a mutated gene. This procedure may be performed between the ninth and 14th week of pregnancy. The risks of infection or damage to the fetus are slightly higher than with amniocentesis. Miscarriage occurs in about two out of 100 women who undergo this procedure. There appears to be an even higher risk of miscarriage when the needle is inserted through the cervix compared with when the needle is inserted through the abdomen. Other factors that further increase the risks of CVS include having multiple procedures and having a fetus that is smaller than normal. The physician's skill and experience also play an important role.
Cordocentesis: Cordocentesis uses a needle to remove blood from the fetus' umbilical cord. This process is very similar to amniocentesis, except that it looks at the blood of the fetus rather than at the amniotic fluid. Miscarriage may occur in about one or two out of 100 patients. Other risks include bleeding, infection, and rupture of membranes.
Preimplantation genetic diagnosis (PGD): Preimplantation genetic diagnosis (PGD) is a test used for embryos in in vitro fertilization. When the embryo comprises fewer than 10 cells, a couple of the cells are removed and sent to a lab. The DNA is tested for genetic abnormalities that are known to cause diseases. The procedure is expensive, costing a few thousand dollars, and may not be covered by insurance. Parents should discuss PGD with their doctors and genetic counselors before having it done.

Complications

Complications vary depending on the type of autosomal dominant disease. For example, complications associated with Huntington's disease include pneumonia and heart disease. Complications associated with Marfan syndrome include cardiovascular, skeletal, and eye problems. Complications associated with familial adenomatous polyposis include bleeding in or blockage of the digestive system and colorectal cancer. Complications that may be seen with neurofibromatosis-1 include blindness, brain tumors, and depression.

Treatment

To date, there are no cures available for autosomal dominant diseases. Treatment instead focuses on reducing symptoms and preventing complications. Individuals known to carry a mutant gene that causes an autosomal dominant disease may be able to take steps to prevent the onset or decrease the severity of symptoms or complications.
Gene therapy: Gene therapy is an experimental technique that may help treat or prevent inherited disorders by providing a "normal" copy of a certain gene. The normal copy would then provide instructions for making "normal" proteins that function properly and prevent disease development. There are several different methods of gene therapy that are currently being studied. In some methods, gene therapy will either replace or inactivate the mutated gene that is causing the disorder. Other gene therapy methods involve inserting a new gene to help the body fight against a specific disease.
Although gene therapy appears to be a promising treatment, further research is needed to determine its safety and effectiveness. Because the safety of gene therapy remains unknown and the treatment is considered "high risk," it is only being studied for the treatment of diseases that have no known cure. Gene therapy products have not been approved for sale in the United States, and the treatment is only available through participation in research studies. Gene therapy is a growing area of research, however, and hundreds of trials are ongoing.

Integrative therapies

Currently, there is a lack of scientific data on the use of integrative therapies for the treatment or prevention of autosomal dominant disease.

Prevention

Because autosomal dominant disorders are inherited, there is no known way to prevent them. However, in some cases, if they are detected early, it is possible to prevent some symptoms or complications.
Genetic testing and counseling: Individuals who have autosomal dominant disorders may meet with genetic counselors to discuss the risks of having children with the disease. Individuals from high-risk populations or those with family histories of autosomal dominant disorders may meet with genetic counselors to determine whether they carry the causative genes.
Individuals with histories of autosomal dominant disorders may choose to undergo genetic counseling before conceiving a child. Genetic counselors can explain the options and the associated risks of various tests, including pre-implantation genetic diagnosis (PGD), amniocentesis, and chorionic villus sampling (CVS). Because certain autosomal dominant disorders can be detected in a growing fetus, parents may choose whether or not to continue the pregnancy. Genetic counselors may assist parents with these difficult decisions.
Some prospective parents may choose not to have children due to the risk of the child inheriting the disorder. Therefore, some individuals may choose to adopt a child or to not have children at all.

Author information

This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

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Causes

Inheritance: Autosomal dominant diseases are caused by mutations, or errors, in a patient's genes. Individuals receive two copies of most genes (one copy from each parent). To inherit an autosomal dominant disorder, an individual need only inherit one copy of the defective gene. If an individual has a parent with one mutant copy, that individual has a 50% chance of inheriting the mutant gene.
To inherit the neurological disorder called Huntington's disease, for example, only one mutant copy of the Huntington gene (referred to as HTT) must be inherited. The one defective copy of the HTT gene leads to production of a defective protein that is toxic to nerve tissue, which causes poor coordination and abnormal body movements distinctive of the disease.
At least 36 other diseases are known to be inherited in an autosomal dominant manner. One example is Marfan syndrome, a connective tissue disorder characterized by abnormally long arms, legs, and fingers and a predisposition to cardiovascular problems. Marfan syndrome is caused by mutations in the FBN1 gene on chromosome 15. Familial adenomatous polyposis, which is caused by mutations in the APC gene on chromosome 5, results in cancer of the large intestine and rectum. Neurofibromatosis type 1, which is characterized by tumors of the nervous tissue and is caused by mutations in the NF1 gene on chromosome 17, is also inherited in an autosomal dominant manner.
Random occurrence: Most cases of autosomal dominant diseases are inherited, meaning that a defective gene is transmitted from parent to child. However, it is possible for these diseases to result from a spontaneously and random mutation in the egg or sperm, during early embryonic development, or even after birth. An individuals who has an autosomal dominant disorder as the result of a spontaneous genetic mutation may pass the condition to his/her children.

Risk factors

Individuals have two copies of most genes (one inherited from the father and one from the mother). In an autosomal dominant genetic condition, only one copy of a certain gene needs to be defective for the condition to develop. If an individual has a parent with one mutant copy, that individual has a 50% chance of inheriting the mutant gene. If one parent has two copies of the mutant gene, there is a 100% chance of inheriting the mutant gene. If each parent has one copy of the mutant gene, there is a 75% chance of the child getting at least one copy of the mutant gene, and therefore, having the disease. Depending on the disease, the symptoms can be more severe if the child inherits two mutant copies of the gene.

Types of the disease

Penetrance: Penetrance is a genetic term used to describe the proportion of individuals carrying a particular variation of a gene (an allele) that also express a particular trait (called the phenotype). For example, mutations in the huntingtin (HTT) gene responsible for Huntington's disease have 95% penetrance, meaning 95% of those with the allele for Huntington's disease develop the disease while 5% do not. Therefore, although Huntington's disease is inherited in an autosomal dominant manner, not every person who inherits the mutated gene will show symptoms of the disease. The degree of penetrance varies between diseases and cannot be predicted by genetic testing.