Chromosomes are the genetic material found in all cells. They consist of proteins and deoxyribonucleic acid (DNA). Each cell has 23 pairs of chromosomes, including one pair of sex chromosomes and 22 pairs of non-sex chromosomes. There are two sex chromosomes, called the X chromosome and the Y chromosome. Females have two X chromosomes, while males have one X chromosome and one Y chromosome. Autosomes are the non-sex chromosomes that are numbered chromosome 1 through 22. Each autosomal gene has two copies and one copy (or allele) is inherited from each parent. Variations of the genes are also known as alleles.
A person inherits genes from his or her parents. One gene is inherited from the mother, and the other gene is inherited from the father. Each parent can only pass one of their genes on to the child. Which gene gets passed down is determined purely by chance. When both alleles of a gene are the same, a person is said to be homozygous for that gene. If different alleles of the gene are inherited from each parent, the person is said to be heterozygous for that gene.
Autosomal recessive disorders are inherited disorders caused by a mutation in a gene. In order to have an autosomal recessive disorder, both copies of the gene (one inherited from each parent) need to contain the mutation. In other words, to be affected by an autosomal recessive disorder, the person needs to be homozygous for that gene. This is different from autosomal dominant disorders, for which a person only needs to inherit one copy of the mutant gene to be affected by the disorder.
When only one mutant gene is inherited in an autosomal recessive disorder, the person does not have the disease and is known as a genetic carrier of the disease. Carriers are able to pass their mutant gene to their children. If both parents are genetic carriers of an autosomal recessive disorder, there is a one in four chance that the child will have the disease. There is a 25% chance the child will have two normal genes and a 50% chance the child will be a carrier and not have the disease. If only one parent has a faulty gene, there is no chance the child will develop the disease. In this case, there is a 25% chance of the child being a carrier. If both parents are affected by an autosomal recessive disorder, then all of their children will most likely have that condition as well.
Cystic fibrosis, Tay-Sachs disease, thalassemia, Gaucher's disease, Wilson's disease, spinal muscular atrophy, and sickle cell disease are all examples of autosomal recessive disorders.
Because males and females share the same autosomal chromosomes, they are affected equally by autosomal recessive disorders. Some autosomal recessive disorders are more common in certain populations. For example, sickle cell disease occurs more frequently in sub-Saharan Africa and other tropical or sub-tropical regions. French Canadians and those of Ashkenazi Jewish descent historically had a higher incidence of Tay-Sachs disease. Among populations that are closely related (or among people who share a common ancestor), autosomal recessive disorders can also be more common.
A child may inherit an autosomal recessive disorder if both parents are carriers of the abnormal gene. If only one parent is a carrier, the child will not inherit the disorder. However, there is a 50% chance that the child will be a carrier.
A child of two carrier parents has a 25% chance of inheriting two abnormal copies of the gene. Thus, each child has a 25% chance of being affected by the disorder. There is a 25% chance the child will inherit both normal genes and neither have the disease nor be a carrier. This means that there is a 50% chance a child will inherit one faulty gene and one normal gene. This child will be a genetic carrier, but will not be affected by the disorder.
If one parent has the disorder (and therefore has two copies of the mutant gene) and the other parent is a carrier, the chance of a child having the disorder increases to 50%. There is also a 50% chance the child will be a carrier and no chance of the child having a normal pair of genes. If both parents have the same autosomal recessive disorder, their children will most likely have the disease.
Each pregnancy holds the same risk, and each child of two carriers has a 25% chance of developing the disease.
General: Currently, there is a significant amount of research devoted to genetic testing for autosomal recessive genes. For some conditions, it is possible to check if a person is a carrier of a recessive disorder. Children and growing fetuses may be tested for some genetic conditions. However, not all genes or genetic disorders can be tested. Ongoing research will increase the number of genes and genetic disorders that can be tested.
Genetic testing is available for several autosomal recessive disorders, including Tay-Sachs disease, cystic fibrosis, Canavan disease, sickle cell anemia, Familial dysautonomia, Niemann-Pick disease, Bloom syndrome, Gaucher disease, Fanconi anemia, and mucolipidosis type IV.
Genetic carrier testing: It is possible to test whether a person is a carrier for certain autosomal recessive disorders. The genetic carrier test will either look at the products of a specific gene or test if the gene itself is faulty. A sample of a person's blood or saliva 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 analyze. The test is usually only performed if there is a family history of an autosomal recessive disorder. This test may also be performed if the parents are of a certain ethnic or cultural background that is associated with an autosomal recessive disorder.
Couples may discuss the decision to get genetic carrier testing with a genetic counselor. Together, they may decide whether carrier testing is appropriate. This test may be performed at any time before, during, or after pregnancy. Reliability of the test depends on what condition is being tested for and to what lab it is being sent.
Diagnostic testing: Genetic testing may be used to diagnose a child that may have an autosomal recessive disorder. Like genetic carrier testing, a sample of saliva and blood is taken from the patient and sent to a lab. At the lab, the sample is tested for a defect in the gene and may take a few days or weeks to analyze. A child that shows signs and symptoms of a disease may get genetic testing to confirm a diagnosis. The patient or parents of the patient may talk with a doctor or genetic counselor if they suspect the child has an autosomal recessive disorder, and they can then decide whether a genetic test is necessary. However, not all diseases can be genetically tested.
Prenatal testing: Prenatal testing may be used to check if a growing fetus has a mutation in the gene or chromosome. Prenatal screening tests may be able to detect if a fetus is at increased risk of getting the disease. Prenatal diagnostic tests may be able to see if a fetus actually has a disorder or is a carrier.
An ultrasound may be used to see if the fetus has any physical abnormalities associated with the 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 specific as other tests. An ultrasound is the least reliable genetic test because it does not look at the actual DNA or chromosomes of the fetus. Sometimes ultrasound may seem normal even if the fetus has the disorder.
Amniocentesis uses a needle to remove amniotic fluid from the sac surrounding the developing fetus. The DNA of the fetus is examined for genetic mutations. Amniocentesis may result in miscarriage, but the incidence is less than that of chorionic villus sampling and cordocentesis. Other risks include infection and injury to the fetus.
Chorionic villus sampling (CVS) looks for genetic defects by removing a small piece of the uterus tissue, called the chorionic villus. This is done by making an incision in the uterus and inserting a small, plastic tube. The sample is used to study the DNA, chromosomes, and enzymes of the fetus, which makes it a more reliable test than an ultrasound. There is a risk of miscarriage, which occurs in about 2% of patients. Other risks include bleeding, infection, and rupture of membranes. This test is used when results are desired early in pregnancy because amniocentesis is performed later in pregnancy.
Cordocentesis uses a needle to take out 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. Polymerase chain reaction is used to multiply the DNA and test for genetic disorders before implantation. 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.
Genetic testing and counseling: Individuals who have autosomal recessive 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 an autosomal recessive disorder may meet with genetic counselors to determine whether they carry the faulty gene.
Carriers can be determined through detailed family histories or by genetic testing. Known carriers of an autosomal recessive disorder may choose to undergo genetic counseling before they conceive 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).
Pre-implantation genetic diagnosis (PGD) may be used with in vitro (artificial) fertilization. In PGD, embryos are tested for the faulty gene in question, and only the embryos that are free of these mutations may be implanted.
Because certain autosomal recessive 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.
Because autosomal recessive disorders are inherited, there is no way to prevent them. Couples may work with genetic counselors to evaluate the probability of having children with autosomal recessive disorders. Counselors may also help prospective parents decide the appropriate testing methods.
Genetic screening is possible through a relatively inexpensive and widely available enzyme assay. Individuals with positive or inconclusive results with the enzyme assay test may undergo DNA testing, which is highly accurate but more expensive.
Having an autosomal recessive disorder or being a carrier can affect a couple's decision to have children. Some parents may not want to have children because of the risk of a child inheriting the disorder. These parents may instead choose to adopt a child or to not have children at all.
For some autosomal recessive disorders, the responsible gene (or genes) may not be known. For genetic disorders, much research focuses on identifying the gene(s) involved, as well as the mutations that are responsible for the disorders. This type of research could help identify carriers of rare diseases. It may also help to diagnose these diseases so that treatment can be started as soon as possible.
The information in this monograph is intended for informational purposes only, and is meant to help users better understand health concerns. Information is based on review of scientific research data, historical practice patterns, and clinical experience. This information should not be interpreted as specific medical advice. Users should consult with a qualified healthcare provider for specific questions regarding therapies, diagnosis and/or health conditions, prior to making therapeutic decisions.