Genetic disorders

This page is intended to provide general information about genetic disorders and more specific information about a few genetic disorders that are diagnosed through the Fetal Concerns Center. It does not provide information about every disorder diagnosed at Children's Wisconsin.

What is genetics and genetic disorders?

Genetics is the study of the pattern of inheritance. A geneticist studies birth disorders and their cause. Normally each individual has 46 chromosomes in every cell. Most fetuses receive 23 chromosomes from each parent. Chromosomes are structures found in every cell of the body. Typically there are 22 non-sex chromosome pairs called autosomes, and one sex chromosome pair. If you are male, the most common sex chromosome pair is XY and if you are female, the most common pair is XX. On each chromosome are hundreds of gene pairs. Genes are the blueprint for human growth and development and tell the cell how to function. Single gene disorders may be autosomal (not sex linked) or X-linked (related to the sex chromosome). Another common classification for genetic disorders is dominant or recessive. Some common genetic disorder classifications are:

• An autosomal dominant disorder may be inherited from one parent who is affected. Dominant means the nonfunctional gene of the gene-pair is able to override the normal gene. A person affected by an autosomal dominant trait has a 50 percent chance of passing it on to his/her offspring.
• An autosomal recessive disorder will most commonly occur when both parents carry the trait and the offspring receives the nonfunctional gene from each parent. Recessive means the traits of the nonfunctional gene are hidden by the normal gene or the normal gene traits override the nonfunctioning gene. A person may carry the nonfunctioning gene but have no symptoms. With an autosomal recessive trait the offspring have a 25 percent chance of inheriting the disorder and having symptoms, a 50 percent chance of receiving a defective gene and thus being a carrier with no symptoms, and a 25 percent chance of not having the disorder and also not being a carrier of the nonfunctioning gene. 
  With an X-linked dominant disorder, affected fathers will transmit the disorder only to their daughters. Affected mothers will have a 50 percent chance of transmitting the disorder to her offspring.
• Finally, an X-linked recessive disorder will typically affect males. A nonaffected female is a carrier who will pass on the disorder to 50 percent of her sons, and 50 percent of her daughters will be carriers. With an affected male, all his daughters will be carriers.

What is a chromosome disorder?

A chromosomal disorder may be inherited or may be sporadic, meaning there is no family history. The most common types of chromosomal disorders can be classified in the following way:

• Aneuploidy means there is the wrong number of chromosomes. This can be too many or too few. Trisomies 13, 18 and 21 are examples of an extra chromosome. These three are the more common ones seen, and the number relates to which extra chromosome they have. For example the Trisomy 21 has three number 21 chromosomes rather than the usual pair. Turner syndrome is an example of too few chromosomes. With Turner syndrome, one of the sex chromosomes is not transferred, leaving a single X chromosome, or 45 rather than the usual 46.
• Deletion means that a part of a chromosome is missing, which ultimately means that the genetic material on the missing section of chromosome is also missing. An example of a deletion syndrome is the Cri du Chat syndrome in which a portion of chromosome 5 is deleted.
• Inversion refers to a chromosome that has broken. The broken piece turns upside down and reattaches itself. Inversions may or may not cause birth defects depending on their exact structure.
• Translocation refers to a rearrangement of a chromosomal segment from one location to another. A balanced translocation has an equal exchange, so no genetic material is added or lost and this person may never be aware of the translocation. For a person with a balanced translocation there is, however, risk to their offspring. The risk is that the chromosome may be passed on as an unbalanced chromosome. An unbalanced translocation means genetic material is added or lost and can cause a variety of problems in varying degrees for the offspring.
• Mosaicism is the presence of two or more chromosome patterns in the cells of a person. This results in two or more cell lines, which means some cells will have 46 chromosomes and some will have a number other than 46 (either greater than or less than 46).
• Sixty percent of all birth defects do not have any known cause. Chromosomal defects account for only about 6 percent of all birth defects. Multifactoral (or a combination of genetics and environmental) inheritance accounts for approximately 20 percent of congenital anomalies. Teratogens are agents that are known to cause birth defects. These can be medications (legal and/or illegal), something in the environment, or a maternal infection. Teratogens cause about 4 to 5 percent of all birth defects.

Prenatal diagnosis of genetic disorder

A genetic disorder may not be suspected unless there is a known family history, anomalies that cause suspicion are noted during an ultrasound, or there are known maternal factors that cause concern, such as an infection, drug ingestion, exposure to a teratogen, maternal health issues, and/or maternal.

There are some prenatal tests that may cause us to look further for a potential problem. Test that can cause us to suspect a problem are called screening tests. These tests reveal the possibility or risk of a problem, but they do not provide a specific diagnosis.

First trimester screening is designed to identify women who may be at increased risk of having a baby with Down syndrome or trisomy 18. It involves a specific ultrasound measurement called "nuchal translucency" and a maternal blood draw. The blood draw measures two chemicals in the pregnant woman's blood. The nuchal translucency is an ultrasound measurement of the amount of fluid accumulation behind the baby's neck. The amounts and patterns of the two chemicals are used, along with the nuchal translucency measurement and the mother's age, to assess the likelihood that a baby would have Down syndrome or trisomy 18. First trimester screening is typically done after 11 and before 14 weeks gestation. Results take approximately 6 to 7 days. A positive screen means that the calculated risk of having a baby with Down syndrome is greater than or equal to a 35-year-old woman's risk. Additional prenatal testing such as chorionic villus sampling (CVS) or amniocentesis would be offered for anyone with a positive screening. These two tests allow us to look at the baby's chromosomes but they cannot tell us everything about the baby. A discussion with your doctor or genetic counselor can help you understand these procedures and the benefits, risk and limitations of these options.

The triple screen or AFP-3 test is a blood test offered to most pregnant women. This test screens for those at increased risk for a baby with a genetic disorder, especially Down syndrome and trisomy 18, or a neural tube defect. This test is typically done after 15 weeks and before 21 weeks' gestation. If you have had first trimester screening it is not recommended that you also need to do this test.

In the triple screen three chemicals are measured from a pregnant woman's blood: alpha-fetoprotein, human chorionic gonadotrophin and estriol. The amount and combination of each of these chemicals help assess risk for Down syndrome, trisomy 18 or neural tube defects. It is important to remember that a positive screen does not mean the baby has one of these disorders. A positive test result means we need to investigate further with additional prenatal testing such as an ultrasound or an amniocentesis. Likewise, a negative screen does not mean the baby has no problems. This screen is for specific birth defects but does not screen for all birth defects.

Diagnostic tests are performed to give a diagnosis. These tests are recommended based on your medical history, family background, a previous test result or results of a screening test. These tests may be more invasive to provide diagnostic information.

Chorionic villus sampling is an invasive test performed at 10 to 12 weeks' gestation. Chorionic villi are microscopic finger-like projections that make up the placenta. The cells from the placenta can give us information about the baby's genes and chromosomes because the baby and the placenta formed from the same fertilized egg. A sample of the chorion is obtained by one of two ways. A small hollow tube may be passed into the vagina and through the cervix, guided by ultrasound to gently take a small sample of the chorionic villi. The other method uses a needle that is inserted through the abdominal wall and is again guided by ultrasound to take the sample. The sample is then tested for chromosomal abnormalities.

Another test for chromosomal abnormalities is amniocentesis. This test is done at 16 to 18 weeks' gestation. This also is an invasive test. A needle is inserted through the abdominal wall into the uterus, and some amniotic fluid is removed and sent to the lab. It will usually take 10-14 days to get the final results. A quick response test is available for some chromosomal disorders. Fluorescence in situ hybridization (FISH) will give us preliminary results in 24 to 48 hours and has been found to be very accurate.

Ultrasound is a noninvasive test performed almost routinely now on all pregnant women. It provides a picture of the baby in the uterus. Ultrasound looks at the anatomy of your fetus. We are now able to visualize babies via ultrasound at younger gestational ages than previously done. We are still learning what is common at these gestational ages. Therefore, if a specific part of the anatomy causes suspicion, we may need to repeat ultrasounds to see if it changes through the process of development. Ultrasound also provides us with information about the position of the baby, amount of amniotic fluid, the position and structure of the placenta, cord position, length of the cervix and can provide more specialized views of blood flow and velocity within the heart and umbilical cord. Ultrasound cannot tell us definitively if your baby has a genetic disorder. It will provide us with information about anatomical disorders.

Things to do before you conceive.

Before you become pregnant you may want to do a few things to ensure your health is at its best. One thing you can do is make a routine physical examination appointment with your primary care provider. At this appointment you will want to verify that you are healthy, your immunization/vaccinations are up to date, review any prescription medications you are taking for safety during pregnancy, test for sexually transmitted diseases and seek treatment if you know you are already infected. You will also want to discuss with your physician your plans to conceive so that they can provide you with information related to pregnancy. 

A vitamin supplement recommended prior to conception that is not normally consumed in a sufficient quantity is folic acid. Folate (the natural form of folic acid found in foods) is found in fortified grains and breakfast cereals, dried beans, orange juice and leafy greens. Synthetic folic acid is more easily used by the body than is folate, the natural form. There is no toxic level of folate. Folate is a B vitamin. Folic acid supplements should be taken for three months prior to the pregnancy and through the first trimester. To ensure that you are getting the daily recommended allowance of folic acid, take a prenatal vitamin daily. The recommended daily allowance (RDA) for folic acid is 0.2 mg. However, all women of childbearing age are encouraged to take 0.4 mg of folic acid supplements because folic acid deficiency is linked to neural tube defects. The RDA for pregnancy is 0.4 mg. For a lactating mother, the RDA is again 0.2 mg. If there is a history of a prior child who has been affected by a neural tube defect, the recommendation for supplementation in future pregnancies is increased to 4 mg a day, beginning at least one month prior to conception and continuing through the first trimester.

Stop smoking before conception or at least reduce the amount of smoking. The more a woman smokes, the greater the risk. Smoking during pregnancy is known to lead to pregnancy complications and serious health problems for the infant. Pregnancy complications can include placental problems such as placenta previa and placental abruption. Smoking can also increase the risk of premature rupture of the membranes, which may result in the birth of a premature infant. Smoking affects the unborn baby as well. As already stated, it can increase the risk of prematurity that carries with it several complications. Smoking slows fetal growth, thus increasing the risk of a low-birthweight (less than 5 1⁄2 pounds) baby.

Also avoiding any type of medications (legal and/or illegal) is recommended. If you currently are on a prescription medication, it is good to discuss your desire to conceive with your physician. Do not stop any prescription medication on your own without first discussing it with your physician. Your physician can help you determine the risks associated with your specific prescription and help you decide if another medication would carry less risk.

It is recommended that pregnant women and women who may become pregnant avoid alcohol consumption even in small amounts. No level of alcohol use has been proven safe during pregnancy. Alcohol consumption during pregnancy can cause physical and mental birth defects. Alcohol passes quickly through the placenta to the fetus. The baby's immature body is slow at breaking down alcohol, resulting in higher alcohol levels that persist for a longer period of time in the fetus as compared to the mother.

If you or your partner have a history of any kind of birth defect in your family or if either of you have already had a child with a birth defect, or if you are in a high-risk group because of age, ethnicity or medical history, you may benefit from a prenatal consultation with a genetic counselor. Through the Fetal Concerns Center, we can set up a consultation appointment with you and your partner to discuss your risk factors with the Genetics Department, or with a maternal fetal medicine specialist. Other reasons for a genetic consult may include a previous stillbirth or multiple miscarriages with no known explanation, family history of mental retardation or developmental delays, or a positive screening test result such as the AFP-3 or triple screen test. You may just want to learn more about testing for recessive genetic diseases that are common in certain ethnic groups or you want to learn more about available testing for genetic diseases or birth defects.

How does the diagnosis of a genetic disorder affect my pregnancy?

What do you do if the test results come back with information you were not expecting, such as your baby has a genetic disorder or birth defect? By knowing the diagnosis before delivery you are given time to process the information, research the care options, and make informed decisions. This does not make the decisions easier, but it gives you time to be more involved in the decisions that will need to be made. You can get input from family, pastors/priests, friends, and medical professionals. You can be an informed decision maker who is actively involved in all aspects of your baby's care. We will be here to provide information at whatever pace you desire, in whatever way is most beneficial to you.

How does a genetic disorder affect my baby?

Listed below is a brief description of some of the more common genetic/chromosomal defects that may be diagnosed prenatally.

Trisomy 13

Trisomy 13 means there are three number 13 chromosomes rather than the usual two. Trisomy 13 has a reported incidence of 1 in 2,200 to 7,600 live births. This chromosomal defect is associated with major congenital anomalies. The most common of which include: holoprosencephaly (the two cerebral hemispheres are fused) or other central nervous system abnormalities, abnormal midface development including clefting, and congenital heart defect. Many fetuses with Trisomy 13 die before they reach term and/or are miscarried. Fifty to eighty percent of infants with Trisomy 13 that are born alive will die by the age of 1 month and 75 to 90 percent have died by age 6 months. Very rarely, affected persons have survived to adulthood.

Trisomy 18

Trisomy 18 is a term used to describe the presence of three number 18 chromosomes rather than the usual two. Trisomy 18 has a reported incidence of 1 in 3,000 to 7,000 live births. This chromosomal defect is associated with major congenital anomalies. The most commonly associated abnormalities include: intrauterine growth restriction, cardiac defects, club foot/feet or rocker bottom feet, and omphalocele. Cranial abnormalities are seen with trisomy 18. These abnormalities include: an unusually shaped head with a wide occipitoparietal and narrow frontal diameter, which has also been described as the "strawberry sign" because of the shape of the head view on ultrasound. Several studies reviewed demonstrated 50% of babies with Trisomy 18 had died by one week of age, and 90 percent by six months. There is a small percentage that will survive beyond infancy. Females are more likely to survive (although not for an extended length of time) than males and the disorder is seen more often in females than males (3:1).

Trisomy 21

Trisomy 21 is a term used to describe the presence of three number 21 chromosomes rather than the usual two. Another name for trisomy 21 is Down syndrome. Down syndrome has a reported incidence of 1 in 800 live births, however the risk of incidence increases with advanced maternal age. The most commonly seen congenital abnormalities include: cystic hygroma (abnormal fluid accumulation around the neck area), nuchal-fold thickness (skin on the back of the neck is thicker than normal), hydrops (abnormal fluid accumulation in two areas of the body such as around the heart, around the lungs, in the abdomen or under the skin), cardiac defects, renal hydronephrosis (part of the kidney has abnormal collection of fluid) and skeletal (bone) abnormalities.

Klinefelter syndrome (47,XXY karyotype)

These are male infants with an extra X chromosome. Many will go undiagnosed until maturity as adults undergoing infertility workups. Fetuses are typically identified during amniocentesis performed for advanced maternal age. They are not normally identified because of an abnormal ultrasound finding. Some information typical of Klinefelter syndrome includes:

• Sons are typically taller than normal (In the 75th percentile on growth charts).
• Puberty will be entered normally but may consider testosterone supplementation therapy after mid-adolescence.
• Sons are infertile.
• Sons are at risk for developmental problems and speech, neuromotor and learning delays.

Achondroplasia

Achondroplasia is an autosomal dominant genetic disorder of bone growth. It affects 1 in 25,000 live births and occurs equally in both sexes and all races. Affected individuals have short arms and legs with a normal torso size. The head is usually large, sometimes due to hydrocephalus, and the forehead is prominent. Achondroplasia is the result of an abnormal gene located on one of the chromosome 4 pair. Eighty percent of these cases are not inherited. Both parents are normal size with normal chromosome 4, but a new mutation occurs for an unknown reason. If one parent has the condition and the other parent does not, their offspring have a 50 percent percent chance of being affected. If both parents have achondroplasia, they have a 50 percent chance of their offspring inheriting the condition, 25 percent chance of not inheriting the condition, and a 25 percent chance of inheriting the abnormal gene from both parents, which results in severe skeletal abnormalities that lead to an early death.

Tay-Sachs disease

Tay-sachs is an inherited disease of the central nervous system that is incompatible with life. A Tay-Sachs carrier has one normal gene and one Tay-Sachs gene making it an autosomal recessive disease. It occurs most frequently in central and eastern European descendants, (Ashkenazi) Jews. Approximately 1 in every 30 American Jews is a carrier of the Tay-Sachs gene. The carrier leads a normal, healthy and full life. Both parents would need to be carriers and each would contribute the affected gene to have an affected baby. A baby with Tay-sachs will appear normal at birth and for approximately 4 to 6 months. The affected baby lacks an enzyme necessary for breaking down certain fatty substances in the brain and nerve cells. At a few months of age the baby will gradually stop smiling, crawling or turning over. Eventually they lose their ability to grasp or reach out and become blind and paralyzed. Death occurs by age 5. If both parents are carriers of Tay-Sachs, their offspring have a 50 percent chance of being a carrier for Tay-sachs; a 25 percent chance of contracting the disease by receiving a defective gene from each parent; and a 25 percent chance of inheriting normal genes from each parent.

Phenylketonuria (PKU)

Phenylketonuria (PKU) is an autosomal recessive, inherited disorder of body metabolism. Metabolism is the process of breaking down food to be used by the body. An affected individual lacks an enzyme necessary to process the protein, phenylalanine. Without treatment this protein builds up in the bloodstream and causes mental retardation. Treatment involves following a special diet that is low in phenylalanine. Since the 1960s, all newborns born in the United States are screened for this disorder shortly after birth. Approximately 1 in every 15,000 babies born is affected. Both parents of these newborns are carriers, but are unaffected. Their offspring have a 50 percent chance of being carriers; 25 percent chance of being affected or inheriting the defective gene from both parents; and a 25 percent chance of inheriting only normal genes from his/her parents. The affected baby appears normal at birth but will develop symptoms of listlessness and lose interest in their surroundings by age 3 to 6 months. The issue today is females who have been diagnosed in infancy with the disease who are now having babies. These women may have begun to eat a normal diet and no longer follow the phenylalanine restrictions. The result is a very high level of phenylalanine in their blood, which can be devastating to their offspring. These women should be counseled prenatally to resume the special diet for at least three months prior to conception and throughout their pregnancy to prevent defects in their babies.

Cystic fibrosis (CF)

Cystic fibrosis (CF) is an autosomal recessive, inherited disorder that affects breathing and digestion. There is no cure. Both parents are carriers but are unaffected. A child with CF has inherited a defective gene from each parent. Future offspring have a 50 percent chance of becoming a carrier or inheriting the defective gene from one parent; a 25 percent chance of being affected; and a 25 percent chance of inheriting only normal genes. With cystic fibrosis the pancreas and lungs are most affected. Mucus and other secretions become thick and sticky. This thick mucous can clog the lungs and causes breathing problems and frequent lung infections, which eventually damages the lungs. The thickened secretions made by the pancreas for digestion of food, are unable to reach the small intestine. This can lead to digestive problems including inability to gain weight or grow at a normal rate. The symptoms of cystic fibrosis will range from mild to severe. Some will attend school and college and participate in some exercise, while others are too ill to attend school regularly. Males affected by CF are commonly infertile and females have reduced fertility. Cystic fibrosis does not affect a person's appearance or intelligence. Most affected individuals survive to 30 or 40 years of age.

Fragile X syndrome

Fragile X syndrome is the most common inherited form of mental retardation in males. It affects 1 in 4,000 males and 1 in 8,000 females. In 1991, a researcher discovered a "mutation" in a gene located on the X chromosome, as the cause of the Fragile X syndrome. Mutation means the addition or deletion of genetic material. A small section of the genetic material at this location is repeated too many times. Normally there are 6 to 40 repeats of this section. If there are 60 to 200 repeats, this is a pre-mutation, and greater than 200 repeats is a mutation. With a mutation the gene will "turn off" and not produce the protein that it normally would make. The lack of this specific protein causes the symptoms of fragile X syndrome. A pre-mutation carrier mother has a 50 percent chance of passing on the abnormal gene to her offspring. Males are generally more severely affected because they have only one X chromosome and one Y chromosome, as compared to a female who has two X chromosomes. As this defective gene is passed on it is likely to expand in the number of repeats and become a full mutation. A man can also be an unaffected carrier of a pre-mutation fragile X gene. This male will pass on the pre-mutation (does not usually expand) to all his daughters but to none of his sons. These daughters generally have no symptoms, but are carriers and may pass it on to their children. Affected individuals have varying degrees of mental retardation or learning disabilities and behavioral and emotional problems, including autistic-like features.

Turner syndrome

Turner syndrome affects only females. It occurs when one of the two X chromosomes normally found in females is missing or incomplete. This, at present, appears to be a random event with no known cause. Turner syndrome is among the most common chromosomal abnormalities affecting 1 in every 2,500 live female births. Most affected females will have normal intelligence. However, 10 percent will have substantial delays and as many as 70 percent will have some mild delays such as learning disabilities. It is believed these women can lead a full and productive life with regular, competent medical care. The most common characteristics of a female with Turner syndrome includes short stature and lack of ovarian development. They are also prone to cardiovascular, kidney and thyroid problems as well as skeletal disorders (scoliosis) and ear and/or hearing disturbances.

How are genetic disorders treated?

Treatment is completely dependent on the disorder or syndrome, the prognosis of the disorder and parental wishes. Some disorders have very short life expectancies for which treatment would not be beneficial. However, some children with genetic disorders can and do function well with normal life expectancies. Others can be variable depending on the associated birth defects. For example, some Trisomy 21 babies can go home from the newborn nursery with minimal problems and others have multiple congenital anomalies that require numerous surgeries and more than one system can be affected. The treatment for these babies will be a collaborative effort of providing information as accurately as we can and allowing you, as the parent, to be the primary decision makers about the care to be provided.

Will I be able to help care for my baby?

Yes! Please ask your baby's nurse about ways to interact with and care for your baby.

If you had planned on breastfeeding your baby, and the baby is unable to eat immediately after birth, you can express your milk while you are still in the hospital. A lactation consultant can assist in answering your questions. Your milk will be frozen until your baby is ready for it. The Birth Center and Neonatal Intensive Care Unit (NICU) have breast pumps available to you when you are in the hospital or visiting. You can bring in pictures, small toys, booties, and blankets for your baby if he/she is in the NICU.

When can my baby go home?

Your baby will go home when you and the medical professionals have deemed it appropriate. Some of these genetic disorders have a short life expectancy. If you are ready to go home and desire to take your baby home with you, knowing they will not have a long-term survival, arrangements can be made for you to continue to care for your baby at home. There are home health services or hospice care that can assist you with care in the home. Some of these babies may have conditions that require surgical repair before he/she can go home. This will prolong the hospital stay for your baby. Some genetic disorders may go undiagnosed for months to years if symptoms are mild. Many of these babies go home from the newborn nursery without any problems until later in life.

Learn more about the Genetics Center at Children's Wisconsin, which works in partnership with the Fetal Concerns Center.