Overview of Genetic Disorders

Some birth defects, such as cleft lip or palate Cleft Lip and Cleft Palate A cleft is an opening that can form in the lip (cleft lip), roof of the mouth (cleft palate), or both if the tissue does not join together completely during pregnancy. Cleft lip and cleft palate... read more , result from abnormalities in one or more genes plus exposure to certain other factors, including substances in the environment (called multifactorial inheritance). That is, the abnormal gene makes the fetus more likely to develop a birth defect, but the birth defect usually does not develop unless the fetus is exposed to specific substances, such as certain drugs or alcohol Overview of Substance-Related Disorders Medications and other substances, whether used for legitimate medical purposes, as a habit (for example, caffeine), or recreationally, are an integral part of everyday life for many people ... read more . Many common birth defects, such as heart malformations, are inherited in this way.

Neural tube defects Neural Tube Defects and Spina Bifida Neural tube defects are a certain type of birth defect of the brain, spine, and/or spinal cord. Neural tube defects can result in nerve damage, learning disabilities, paralysis, and death. The... read more are birth defects of the brain or spinal cord. (The brain and spinal cord develop from a part of the embryo called the neural tube). Examples are spina bifida (in which the spine does not completely close, sometimes exposing the spinal cord) and anencephaly (in which a large part of the brain and skull is missing). In the United States, neural tube defects occur in about 1 in 1,000 births. For most of these defects, inheritance is multifactorial (abnormal genes plus other factors). Other factors include

A few neural tube defects result from hereditary abnormalities in a single gene, from chromosomal abnormalities, or from exposure to drugs.

Counseling about prenatal diagnosis by amniocentesis Amniocentesis Prenatal diagnostic testing involves testing the fetus before birth (prenatally) to determine whether the fetus has certain abnormalities, including certain hereditary or spontaneous genetic... read more and ultrasonography Ultrasonography Prenatal diagnostic testing involves testing the fetus before birth (prenatally) to determine whether the fetus has certain abnormalities, including certain hereditary or spontaneous genetic... read more is recommended for couples who have at least a 1% risk of having a baby with a neural tube defect.

Many chromosomal abnormalities Overview of Chromosome and Gene Disorders Chromosomes are structures within cells that contain a person's genes. A gene is a segment of deoxyribonucleic acid ( DNA) and contains the code for a specific protein that functions in one... read more , mainly those involving an abnormal number of chromosomes or an abnormality in a chromosome's structure, can be detected by standard chromosomal testing. These abnormalities occur in about 1 of 250 live births in the United States and account for at least half of all miscarriages that occur during the 1st trimester. Most fetuses that have chromosomal abnormalities die before birth. Among live-born babies, Down syndrome Down Syndrome (Trisomy 21) Down syndrome is a chromosome disorder caused by an extra chromosome 21 that results in intellectual disability and physical abnormalities. Down syndrome is caused by an extra chromosome 21... read more is the most common chromosomal abnormality.

Several factors increase the risk of having a baby with a chromosomal abnormality:

Some chromosomal abnormalities cannot be detected by standard chromosomal testing. Most of these abnormalities are too small to be seen with a microscope, so they are sometimes called submicroscopic abnormalities (or copy-number variants). For example, a very small part of a chromosome may be missing (called a microdeletion), or a chromosome may have a very small extra part (called a microduplication). How often microdeletions and microduplications occur is unknown. However, about 6% of children with structural birth defects have them, even though results of standard chromosomal testing are normal. Tests called chromosomal microarray testing can detect microdeletions and microduplications. Doctors may offer microarray testing before birth in certain circumstances—for example, when birth defects are suspected in a fetus.

In single-gene disorders, only one pair of genes is involved. A gene may have a mutation, which interferes with its normal function and can lead to disease or birth defects. The risk of such disorders depends on whether the disorder develops when only one gene in the pair has a mutation (such genes are dominant Dominant disorders Genes are segments of deoxyribonucleic acid (DNA) that contain the code for a specific protein that functions in one or more types of cells in the body. Chromosomes are made of a very long strand... read more ) or when both genes must have mutations (such genes are recessive Recessive disorders Genes are segments of deoxyribonucleic acid (DNA) that contain the code for a specific protein that functions in one or more types of cells in the body. Chromosomes are made of a very long strand... read more ).

Risk also depends on whether the gene is located on the X chromosome. There are 23 pairs of chromosomes. One pair, the X and Y chromosomes (sex chromosomes), determines sex. All the rest of the chromosomes are called autosomal chromosomes. Women have two X chromosomes, and men have one X chromosome and one Y chromosome. If the abnormal gene is located on the X chromosome, the disorder it causes is called an X-linked X-Linked Inheritance Genes are segments of deoxyribonucleic acid (DNA) that contain the code for a specific protein that functions in one or more types of cells in the body. Chromosomes are made of a very long strand... read more (sex-linked) disorder.

If boys inherit an abnormal gene for an X-linked disorder (on the X chromosome), they have the disorder even if the gene is recessive because they have only one X chromosome, which has an abnormal gene. They do not have a normal X chromosome to override the one with the abnormal gene. If a male fetus inherits a dominant X-linked gene, the pregnancy typically ends in miscarriage Miscarriage A miscarriage is the loss of a fetus before 20 weeks of pregnancy. Miscarriages may occur because of a problem in the fetus (such as a genetic disorder or birth defect) or in the woman (such... read more .

However, girls must inherit two abnormal genes to develop an X-linked disorder if the gene is recessive. If the abnormal gene is dominant, only one abnormal gene is required for the disorder to develop.

If the prospective mother and father are related, they are more likely to have the same mutation in one or more of the genes that cause autosomal recessive disorders. Thus, the risk of such disorders is increased.