women s health issues
Overview of Genetic Disorders
Risk Factors for Genetic Disorders or Birth Defects
All pregnancies involve some risk of genetic abnormalities. The following percentage of all babies have an abnormality: 0.5% have a chromosomal disorder. 1% have a single-gene (mendelian) disorder. 1% have a disorder caused by defects in several genes. The percentage of stillborn babies with an abnormality is even higher. However, certain conditions increase risk. Some birth defects, such as Cleft Lip and Cleft Palate , 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 Neural Tube Defects and Spina Bifida 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 Family history:The risk of having a baby with a neural tube defect is increased by having a family member, including the couple’s children, with such a defect (family history). For couples who have had a baby with spina bifida or anencephaly, the risk of having another baby with one of these defects is 2 to 3%. For couples who have had two children with one of these defects, the risk is 5 to 10%. However, about 95% of neural tube defects occur in families without a history of neural tube defects. Folate Deficiency : Geographic location:Risk also varies based on where a person lives. For example, risk is higher in the United Kingdom than in the United States. 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 and Many Overview of Chromosome and Gene Disorders , 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, Several factors increase the risk of having a baby with a chromosomal abnormality: Woman’s age:The risk of having a baby with Down syndrome increases with a woman’s age—steeply after age 35. The chance of having a baby with Down syndrome is about 1 in 365 at age 35 and 1 in 100 at age 40. Family history:Having a family history (including the couple’s children) of a chromosomal abnormality increases the risk. If a couple has had one baby with the most common form of Down syndrome (trisomy 21) and the woman is younger than 30, the risk of having another baby with a chromosomal abnormality is increased to about 1%. Having had a live-born baby with a Overview of Birth Defects or a Previous Miscarriage : Chromosomal abnormality in a prospective parent:Rarely, a prospective parent has a structural chromosomal abnormality that increases the risk of having a baby with a structural chromosomal abnormality. A chromosomal abnormality in one or both parents increases the risk, even if the affected parent is healthy and has no physical sign of the abnormality. Doctors suspect such an abnormality when couples have had several miscarriages, problems with infertility, or a baby with a birth defect. For such couples, the risk of having a baby with a serious chromosomal abnormality is increased, as is the risk of miscarrying. The chance of having a baby with Down syndrome at age 35 is about 1 in 365. The chance of having a baby with Down syndrome at age 40 is about 1 in 100. 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 disorders ) or when both genes must have mutations (such genes are 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 Inheritance (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 . 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. 