Most babies are born healthy, but for some there is an increased risk of a birth defect. Testing can help detect the risk of a genetic disorder, but no test is 100% accurate.

Chromosomes and Genes

Genetics is the study of how traits—such as blood type—are passed from parent to child through genes and chromosomes. Each cell in your body has pairs of genes and chromosomes. They control your physical makeup.

Normally, a man's sperm and a woman's egg have 23 chromosomes each. All other cells in the body have 46. When an egg is fertilized by a sperm, 23 chromosomes from the mother and 23 chromosomes from the father join to form the 46 chromosomes of the cell that will become the fetus.

One pair of these chromosomes—one each from the sperm and the egg—is the sex chromosomes. There are two types of sex chromosomes: X and Y. A normal sperm has either an X or a Y chromosome. A normal egg always has an X chromosome.

The sex chromosome in the sperm determines the sex of the child. If a sperm with a Y chromosome joins with an egg, the fetus is male (XY). If the sperm has an X chromosome, the fetus is female (XX).

Each chromosome carries many genes. Genes also come in pairs. Half of a fetus's genes come from the mother. The other half come from the father. Some traits, such as blood type, are determined by a single gene pair. Other traits—including skin color, hair color, and height—are the result of many pairs of genes working together. A gene or a genetic disorder is either dominant or recessive. If one gene in a pair is dominant, the trait it carries cancels out the trait carried by the recessive gene. For a recessive trait to appear, the gene that carries it must be inherited from both parents.

Types of Genetic Disorders

Genetic disorders may be caused by problems with either genes or chromosomes. An inherited disorder is caused by a gene that is passed from parent to child. These disorders can be dominant, recessive, or X-linked. Chromosomal disorders can occur even when the parents do not have any risk factors. Some are caused by a mix of factors (multifactorial).

Dominant Disorders

Just one gene from either parent can cause a dominant gene disorder. If one parent has the gene, each child of the couple has a 1-in-2 chance of inheriting the disorder. Examples of dominant disorders are:

• Huntington's disease. An inherited nerve disorder that causes loss of control of movements and mental function, usually starting between 35–50 years of age.
• Polydactyly. A condition in which a person has extra fingers or toes.

For recessive disorders, both parents must carry the gene before the problem can occur in their child. If you have a recessive gene for a certain disorder, you are a carrier for that disorder. Although you may show no signs of the disorder yourself, you can still pass it on to your children. If both parents are carriers of the same recessive disorder, each of their children has a 1-in-4 chance of having the disorder. Some recessive disorders are more common in certain ethnic groups, such as:

• Sickle cell disease. An inherited disorder in which red blood cells have a crescent shape, causing chronic anemia and episodes of pain. It occurs most often in African Americans.
• Tay–Sachs disease. An inherited birth defect that causes mental retardation, blindness, seizures, and death, usually by age 5 years. It occurs mostly in people of eastern European Jewish descent (Ashkenazi Jews) and among French Canadians and Cajuns.
• Cystic fibrosis. An inherited disorder that causes problems in digestion and breathing that occurs mostly in people of Northern European descent.

X-Linked Disorders

Disorders that are caused by genes on the X chromosome are called X-linked or sex-linked disorders. In most X-linked disorders, the abnormal gene is recessive.

A woman can carry the gene for an X-linked disorder caused by a recessive gene but not have that disorder. This is because even though one of her X chromosomes has the recessive disorder, her other X chromosome has the normal gene, which is dominant.

A male baby inherits one X chromosome from his mother. If the X chromosome he inherits has the disorder, he will get the disorder because he doesn't have another X chromosome with a normal gene to cancel out the abnormal one. Color blindness is a common X-linked trait.

If you are a carrier for an X-linked disorder, there is a 1-in-2 chance a son will have the disorder and a daughter will be a carrier. Very rarely, a daughter has an X-linked recessive disorder. In this case, her father has the disease and her mother is a carrier.

If you have a family history of a disorder, carrier testing may be used to show if you are a carrier of an X-linked disorder. Examples of X-linked disorders are:

• Hemophilia. An inherited sex-linked disorder in which the blood lacks a substance that helps it clot.
• Duchenne muscular dystrophy. An inherited, sex-linked disease most often affecting males. Symptoms are weakness and muscle wasting, first of the limbs and trunk, but slowly affecting all voluntary muscles, with death usually occurring around age 30 years.
• Fragile X syndrome. A disorder of the X chromosome that is the most common inherited cause of mental retardation.

Genetic disorders also may be caused by a missing, damaged, or extra chromosome. Such problems often are caused by an error that occurred when the egg or sperm was forming. Most children with chromosomal disorders have physical defects, and some have mental defects. Two examples of chromosomal disorders are:

• Down syndrome. A genetic disorder resulting from an extra copy of the 21st chromosome in which mental retardation, abnormal features of the face, and medical problems such as heart defects occur.
• Trisomy 18. A genetic disorder resulting from an extra copy of the 18th chromosome that causes serious problems with physical and mental development. Most infants with trisomy 18 die within the first year of life. The risk of having a child with a chromosomal disorder increases as a woman ages. For instance, a 35-year-old woman has a 1-in-192 (less than 1%) chance of having a baby with a chromosomal disorder. The chance increases to 1 in 66 (about 1.5%) in a woman aged 40 years.

Multifactorial Disorders Disorders thought to come from a mix of factors are called multifactorial disorders. This means the actual cause is unknown. A few of these disorders can be detected during pregnancy. Sometimes they can be corrected with surgery. Some examples of multifactorial disorders are: Abdominal wall defect: The muscle and skin that cover the wall of the abdomen are missing and the bowel is either enclosed in a clear sac (omphalocele) or sticks out through a hole in the abdominal wall (gastroschisis). Cleft palate: A gap or space occurs in the roof of the mouth. Clubfoot: The foot is misshaped and twisted out of position. Neural tube defect: Incomplete closure of the fetal spine that can result in spina bifida or anencephaly. How Common Are Chromosomal Disorders? Because the risk of chromosomal disorders increases with age, women 35 years and older are offered tests to find out if their babies may have a problem. Mother's Age Risk of Down Syndrome Risk of Any Chromosomal Disorder 20 1/1,667 1/526 25 1/1,250 1/476 30 1/952 1/385 35 1/378 1/192 36 1/289 1/156 37 1/224 1/127 38 1/173 1/102 39 1/136 1/83 40 1/106 1/66 41 1/82 1/53 42 1/63 1/42 43 1/49 1/33 44 1/38 1/26 45 1/30 1/21 Modified from Hook EB, Cross PK, Schreinemachers DM. Chromosomal abnormality rates at amniocentesis and in live-born infants. JAMA 1983;249:2034–2038 (ages 33–49), copyrighted © 1983, American Medical Association. All rights reserved; Hook EB. Rates of chromosome abnormalities at different maternal ages. Obstet Gynecol 1981;58:282–285. Risk Factors When you have your prepregnancy checkup or start prenatal care, your doctor may give you a list of questions like the ones in the box "Risk Factors for Genetic Disorders." Your answers to these questions will help your doctor advise you on your risk of having a baby with a genetic defect. He or she also may suggest genetic counseling or testing. If you answer "yes" to any of them, you may be at increased risk for having a baby with a genetic disorder. In most cases, even couples at risk can have healthy children with no genetic disorders. However, genetic disorders can occur even when there is no history of problems in the family. For that reason, some tests to detect genetic disorders are offered to all women. Testing Whether you want to be tested to see if you are at increased risk for birth defects or genetic disorders is a personal choice. Some couples would rather not know if they are at risk for a problem, but others benefit from knowing in advance. Some tests can be done before a woman is pregnant and others are done at various times during pregnancy. Some may need to be done in a special center equipped to perform them. Carrier Testing Carrier testing of both parents will detect if either parent is a carrier of a certain genetic defect. Carrier testing can be done before, during, or after pregnancy. Risk Factors for Genetic Disorders Will you be 35 years or older when your baby is due? Will the baby's father be 50 years or older when your baby is due? If you or your partner are of Mediterranean, Asian, or African descent, do either of you or anyone in your families have thalassemia (an inherited disorder that causes anemia)? Is there a family history of neural tube defects? Have you or the baby's father ever had a child with a neural tube defect? Is there a family history of congenital heart defects? Is there a family history of Down syndrome? Have you or the baby's father ever had a child with Down syndrome? If you or the baby's father are of eastern European Jewish, French Canadian, or Cajun descent, is there a family history of Tay–Sachs disease? If you or the baby's father are of eastern European Jewish descent, is there a family history of Canavan disease? If you or the baby's father are African American, is there a family history of sickle cell anemia or sickle cell trait? Is there a family history of hemophilia? Is there a family history of muscular dystrophy? Is there a family history of cystic fibrosis? Is there a family history of Huntington's disease? Does anyone in your family or the family of the baby's father have cystic fibrosis? Is anyone in your or the baby's father's family mentally retarded? If so, was that person tested for fragile X syndrome? Do you, the baby's father, anyone in your families, or any of your children have any other genetic diseases, chromosomal disorders, or birth defects? Do you have a metabolic disorder such as type 1 or type 2 diabetes or phenylketonuria? Do you have a history of pregnancy issues (miscarriages or a stillborn baby)? For a carrier test, a sample of blood or saliva is studied in a lab to detect a defective gene for a certain inherited disorder. All women may be offered or informed about carrier testing for cystic fibrosis. Other tests can be done if your family history, ethnic origin, or some other factor raises your risk of being a carrier. Unfortunately, there are no carrier tests for most inherited birth defects. Your doctor or genetic counselor will help you understand the chances that the defect could be passed on to your baby. If the carrier testing is done before you are pregnant, you can use the results to decide if you want to get pregnant. If you are already pregnant, you may be offered testing to see if the baby has the defect. Genetic Counseling Genetic counseling can help you and your partner find out if you are at risk for having a baby with a disorder. A genetic counselor has special training in genetics. He or she can work with you and your partner to give you expert advice on types of genetic disorders and how they affect the babies born with them. A genetic counselor will ask you and your partner for a detailed family history and may refer you for physical exams and tests. Using this information, the counselor will assess your baby's risk of having a problem, discuss your options, and talk about any concerns you may have. Screening Tests Screening tests are available to detect some birth defects during pregnancy. However, a screening test only shows if there is an increased risk that a defect will occur. The following screening tests may be offered: Maternal serum screening. These tests measure the level of three or four substances in the mother's blood. This test is used to find out if a woman is at increased risk for having a baby with a neural tube defect, abdominal wall defect, Down syndrome, or trisomy 18. These tests usually are done between 15 and 20 weeks of pregnancy. First trimester screening. This screening test combines the results of a special ultrasound test called nuchal translucency screening and blood (serum) tests (PAPP-A and hCG). It is done between 10 and 14 weeks of pregnancy. This test can be done to look for signs of Down syndrome, trisomy 18, and heart defects. A test result could be positive (showing there is a risk of a problem) even though the baby is healthy. Likewise, a birth defect can occur even if testing doesn't show a problem. Most tests focus on a certain problem, and not all disorders can be found by testing. If the results of a screening test show an increased risk, further tests may be done to diagnose the problem. Diagnostic Tests If a screening test or other factors raise concerns, diagnostic tests often can show whether certain birth defects are present. The following diagnostic tests may be offered: Detailed ultrasound exam. A type of ultrasound exam that can help explain abnormal screening test results and provide more detailed information. An ultrasound exam can be performed anytime during pregnancy, although a detailed exam is best performed after 18 weeks of pregnancy. Amniocentesis. A procedure in which a needle is used to withdraw a small amount of amniotic fluid and cells from the sac surrounding the fetus. The amniotic fluid and cells can be tested to detect certain chromosomal problems in the fetus. Amniocentesis usually is done at 15–20 weeks of pregnancy. Chorionic villus sampling (CVS). A procedure in which a small sample of cells is taken from the placenta and tested. CVS detects some of the same chromosomal problems as amniocentesis does. This test can be performed earlier than amniocentesis—often at 10–12 weeks of pregnancy. Fetal blood sampling. Also known as cordocentesis, this procedure tests for chromosomal defects and other problems. For this test, blood is taken from a vein in the umbilical cord. Fetal blood sampling usually is used when the results of amniocentesis, chorionic villus sampling, or ultrasound are unclear. The test results may take a week or more to complete. The Next Steps The results of these tests and what they mean to the mother and baby can be explained by a genetic counselor. These counselors have special skills in genetic disorders. They are trained to assess risks and help couples in looking at their options. Finally . . . Most babies are born healthy, but for some there is an increased risk of a birth defect. Testing can help detect the risk of a genetic disorder, but no test is 100% accurate. If you are at risk for having a baby with a genetic disorder, talk to your doctor about counseling and testing. A counselor can give a couple information that can help them decide how to proceed. Glossary Anencephaly: A type of neural tube defect that occurs when the fetus's head and brain do not develop normally. Chromosomes: Structures that are located inside each cell in the body and contain the genes that determine a person's physical makeup. Fetus: A baby growing in the woman's uterus. Genes: DNA "blueprints" that code for specific traits, such as hair and eye color. Nuchal Translucency Screening: A special ultrasound test of the fetus to screen for the risk of Down syndrome and other birth defects. Spina Bifida: A neural tube defect that results from incomplete closure of the fetal spine. Ultrasound: A test in which sound waves are changed to images to examine internal structures. During pregnancy, it can be used to examine the fetus. This Patient Education Pamphlet was developed under the direction of the Committee on Patient Education of the American College of Obstetricians and Gynecologists. Designed as an aid to patients, it sets forth current information and opinions on subjects related to women's health. The average readability level of the series, based on the Fry formula, is grade 6–8. The Suitability Assessment of Materials (SAM) instrument rates the pamphlets as "superior." To ensure the information is current and accurate, the pamphlets are reviewed every 18 months. The information in this pamphlet does not dictate an exclusive course of treatment or procedure to be followed and should not be construed as excluding other acceptable methods of practice. Variations taking into account the needs of the individual patient, resources, and limitations unique to the institution or type of practice may be appropriate. Copyright © March 2005 by the American College of Obstetricians and Gynecologists. All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without prior written permission from the publisher. ISSN 1074-8601 Requests for authorization to make photocopies should be directed to the Copyright Clearance Center, 222 Rosewood Drive, Danvers, MA 01923. 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