Genetic disorders

Genetic or inherited disorders can be passed from one generation to the next.


Understanding genes and chromosomes
Abnormal genes or chromosomes cause genetic disorders. Genes are the basic units of heredity. They determine physical and mental characteristics. Genes are grouped together in a specific order along strands known as chromosomes. With the exception of the egg and sperm cells, each body cell has 46 chromosomes and contains about 100,000 genes.
Egg and sperm cells have 23 chromosomes -- half the usual number of normal body cells. The egg and sperm cells develop from cells that contain the normal 46 chromosomes. Early in their development, however, they divide in half and form two cells, each containing half of the chromosomes from the original cell. Later, when a woman's egg cell and a man's sperm cell unite to form a zygote (the first cell of a fetus), the 23 chromosomes in the egg cell pair up with the 23 chromosomes in the sperm cell and create the 46 chromosomes in the zygote.

Dominant vs. recessive genes
Forty-four of the chromosomes are known as autosomes, and the remaining two are the sex chromosomes. Each autosome from the egg pairs up with a corresponding autosome from the sperm. The paired autosomes contain genes for the same characteristics located in exactly the same places along their structures. Physical and mental characteristics are determined by the combination of these genes from the egg and sperm. If the two genes are different, the dominant gene will determine the characteristic. A recessive gene must be paired with another recessive gene for a person to develop that particular characteristic.

To more clearly understand the principle of dominant and recessive genes, consider the example of hair color. Genes for brown hair are dominant over genes for blond hair. If a child receives the dominant gene for brown hair from both parents, or a dominant gene for brown hair from one parent and a recessive gene for blond hair from the other, the child will have brown hair. If the child receives two recessive genes for blond hair, however, he or she will have blond hair.

When egg cells are formed in a woman and sperm cells in a man, they are not all alike. For example, if a woman receives a gene for brown hair from one parent and a gene for blond hair from the other, some of her egg cells will have the gene for brown hair and others will retain the gene for blond hair. Even if she has brown hair, she can pass on the recessive gene for blond hair to her own biological children.

Determining sex
The two sex chromosomes -- the X chromosome and the Y chromosome -- determine the sex of the fetus. The X chromosome is longer and contains genes that do not have a corresponding gene in the shorter Y chromosome. A fetus will be female if it receives two X chromosomes. It will be male if it receives an X and a Y chromosome.


Causes/associated factors
A single abnormal gene, an abnormal structure or number of chromosomes, or a combination of genetic and environmental factors can cause genetic disorders. Not all of these disorders are serious, but some can be detrimental to a baby's health. Others are incompatible with life. In fact, genetic abnormalities are found in up to 50 percent of all miscarriages.
Single-gene disorders
One abnormal gene can lead to a genetic disorder. Such disorders are described by the type of chromosome on which the gene is found (autosomal or sex) and by the gene's dominance over its corresponding gene (dominant or recessive). Most genetic disorders are passed on through recessive genes.

Again, the X chromosome contains genes that do not have a corresponding gene in the Y chromosome. Disorders passed on through these genes are referred to as X-linked disorders. They may be passed on to sons and daughters differently, depending on the sex of the parent who passes on the gene.

For some disorders, genetic testing can determine if a person has the abnormal gene. There are four different types of single-gene disorders:

Autosomal dominant disorders occur when the abnormal gene is dominant and located on an autosome. In this type of disorder, only one parent needs to have the abnormal gene. That parent will have the disorder or will eventually develop it if the disorder typically appears later in life. Often, there is a family history of the condition.

The parent with the disorder most often has one abnormal dominant gene and a corresponding normal gene, either of which can be passed on to his or her biological children. In this case, the risk of passing on the abnormal gene and, thus, the disorder, is 50 percent. If the parent has two abnormal dominant genes for the disorder, the abnormal gene would be passed on to all of his or her biological children, who will then develop the condition.

Examples of autosomal dominant disorders:

Achondroplasia, a disorder of bone growth that causes a person to be abnormally short and have certain abnormal body proportions.

Huntington's disease, a fatal neurological disease that begins after age 35 and leads to loss of motor control and intellectual deterioration.

Neurofibromatosis, a disease characterized by the growth of tumors (abnormal tissue growths) on various nerves in the body. The effects of these tumors vary, from going unnoticed to causing serious disability.

Marfan's syndrome, a disease that affects the connective tissue, which holds other tissues together. The eyes, heart, blood vessels and skeleton are often affected.

Osteogenesis imperfecta, a serious disease that produces fragile bones that break very easily.
Autosomal recessive disorders occur when the abnormal gene is recessive and located on an autosome. Both parents must pass on the abnormal recessive gene for the child to develop the disorder. If the child receives one normal gene and one abnormal gene, the normal gene is dominant and the child will not develop the condition. With this type of disorder, neither parent is usually affected by the disorder. There may also be no family history of the condition.

Parents who do not have the disorder but do have the recessive gene that can be passed on to their biological children are called carriers. When both parents are carriers, their biological children have a 25-percent risk of developing the disorder and a 50-percent risk of becoming carriers.

If one parent has the disorder and the other is a carrier of the recessive gene, their biological children have a 50-percent risk of developing the disorder or becoming carriers. If one parent has the disorder and the other parent is not a carrier of the recessive gene, their biological children have no risk of developing the disorder. They will all be recessive gene carriers, however, and could pass the gene on to their own biological children.

Examples of autosomal recessive disorders:

Cystic fibrosis, a disease in which the body produces thick, sticky mucus that affects the lungs and pancreas. This leads to breathing problems, frequent lung infections, poor weight gain and other problems. The average life expectancy of someone with cystic fibrosis is age 30.

Phenylketonuria (PKU), a disease that prevents the body from processing a specific part of protein called phenylalanine. The buildup of this substance in the body leads to mental retardation if the child does not have a special diet from birth.

Sickle cell disease, a disease that causes the development of abnormal red blood cells. This leads to anemia (a lack of red blood cells, which carry oxygen to all the body cells) and damage to important body organs. Sickle cell disease is sometimes fatal.

Tay-Sachs disease, a disease that can gradually destroy the brain and nerve cells and eventually prove fatal. A milder form can lead to muscular problems and mental illness.

Thalassemia, a disorder that causes several forms of anemia.

Albinism, a disorder that causes an absence of pigment (coloring) in the skin, hair and eyes.
X-linked dominant disorders are rare, but they occur when the abnormal gene is dominant and located on the X chromosome. With this type of disorder, only one parent needs to have the abnormal gene. That parent will have the condition, and all biological children who receive the X chromosome with the abnormal gene will also develop the disorder.

X-linked recessive disorders occur when the abnormal gene is recessive and located on the X chromosome. Mothers are considered carriers of this type of disorder and can pass it on to their biological sons. In rare cases, these disorders affect biological daughters and are fatal before or at birth.

To understand this pattern of inheritance, it's important to remember there are two sex chromosomes, the X and Y chromosomes. The X chromosomes are longer and contain genes that don't have corresponding genes in the shorter Y chromosomes. Women have two X chromosomes. Men have one X chromosome and one Y chromosome. Women can pass either X chromosome on to their biological children, regardless of sex. Men pass their X chromosome on to their biological daughters and their Y chromosome on to their biological sons.

A mother who has only one X chromosome with the abnormal gene can pass that chromosome on to 50 percent of her biological children. If a son receives the affected X chromosome, he will not have a corresponding dominant normal gene on his Y chromosome to block the recessive abnormal gene. Therefore, he will always be affected by the disorder and never be just a carrier of the gene. If he has biological children, he will always pass the affected X chromosome on to his daughters, but his sons are not affected.

A daughter who receives an X chromosome with an abnormal recessive gene from one of her parents will have a corresponding gene on the X chromosome she receives from the other parent. If the other gene is a dominant normal gene, then she will be protected from the disorder. She will become a carrier of the abnormal gene, however. If the other gene is also an abnormal recessive gene, she will not survive.

Examples of X-linked recessive disorders:

Color blindness, a disorder in which certain colors cannot be distinguished.

Hemophilia A and B, disorders in which certain blood factors necessary for blood clotting are missing. This leads to easy bleeding, which can be life-threatening.

Duchenne's muscular dystrophy, a disease that causes gradual weakening of the body muscles. Respiratory or heart complications eventually lead to disability and death at an early age.
Chromosomal abnormalities
The second category of genetic disorders is due to chromosomal abnormalities. These may be due to an error in chromosomal number or structure. This, in turn, produces an excess or lack of genetic information.

Chromosomal abnormalities can occur during the formation of the egg and the sperm cells or can develop later. Remember, the egg and sperm cells originally contain 46 chromosomes, but they divide early in their development, with half of the chromosomes going into one cell and half into another. If the chromosomes don't divide evenly, too few chromosomes will be present in one of the resulting cells and too many in the other. When one of these abnormal egg or sperm cells unites with a normal cell, the resulting zygote will also have too few or too many chromosomes. A fetus with too few chromosomes will not survive, and a fetus with too many chromosomes will have a genetic disorder.

Chromosomes can also break during cell division, creating cells that contain too much or too little of the chromosome. Sometimes a cell may contain the normal number of chromosomes, but one will become abnormally attached to another. Other chromosomal disorders result from exposure to such things as radiation and certain drugs during the formation of the fetus. Such exposure can also lead to abnormal cell division and abnormal chromosomes.

Examples of genetic disorders due to chromosomal abnormalities:

Down syndrome (trisomy 21), a syndrome caused by an extra number 21 chromosome. It's a combination of defects leading to some degree of mental retardation and characteristic facial features. The heart, eyes and hearing may also be affected.

Turner's syndrome, a syndrome caused by errors in one of the X chromosomes. This disorder leads to multiple problems involving different organs, such as the heart, bones, urinary tract and thyroid gland. There may also be problems with growth and fertility.

Klinefelter's syndrome, a syndrome that results from an extra X chromosome in males. It involves hormonal imbalances, which cause characteristic changes in the sexual organs and body proportions.

Cri-du-chat (kitten's cry), a syndrome caused by the absence of part of chromosome 5. It is named for the characteristic kitten-like cry of the child. It leads to severe mental retardation.
Disorders involving hereditary and environmental factors
The third category of genetic disorders, the most common form, results from what's called "multifactorial inheritance." These disorders are not clearly linked to one gene or chromosome abnormality. Instead, more than one gene or factor may be involved, making people more susceptible to certain diseases. Environmental factors may also increase the susceptibility to the condition. This type of disorder may run in families.

Examples of multifactorial inheritance disorders:

Congenital heart defects, ranging from very mild to very severe. Several tend to run in families. Environmental factors -- such as the virus that causes rubella (German measles), certain medications, alcohol, cocaine and diabetes in the mother -- may also contribute to the development of certain heart defects. Others are part of other congenital syndromes, such as Down syndrome. Examples of heart defects include:
septal defects (a hole between either the upper or lower chambers of the heart that increases the heart's workload)
coarctation of the aorta (narrowing of the large artery carrying blood from the heart)
heart valve abnormalities (affecting the valves that regulate the flow of blood between the heart chambers)
Tetralogy of Fallot (a combination of defects that disrupt blood flow from the heart to the lungs)

Neural tube defects, affecting the tissue that becomes the brain and spinal cord in the fetus. An example of this type of defect is spina bifida, in which part of the baby's spine remains open, leaving the spinal cord unprotected. If the defect is small, there may be no symptoms. Severe defects may cause paralysis of the legs. Another neural tube defect is anencephaly, the absence of part or all of the brain. This condition is fatal before or soon after birth. neural tube defects appear to have genetic as well as environmental causes. Adequate folic acid (vitamin B6) in the mother's diet before conception and during the first trimester has been found to help protect babies from neural tube defects. A folic acid supplement is now recommended for all women of childbearing age.

Pyloric stenosis, a narrowing of the lower part of the stomach, which prevents normal passage of an infant's food into the intestines. This may lead to vomiting, dehydration and malnutrition.

Cleft lip and cleft palate, a malformation of the lip or palate, involves an opening in the upper lip or the roof of the mouth. This may lead to feeding problems, frequent ear infections, dental problems and speech difficulty.

Clubfoot, a disorder in which the foot is twisted out of shape or position.

Congenital dislocation of the hip, a disorder that involves abnormal hip joint development.

Risk of specific disorders
Autosomal recessive disorders

Cystic fibrosis: 1 in 2,000 births (for people of northern European descent)
PKU: 1 in 12,000 births
Chromosomal disorders

Down syndrome: This is the most common genetic disorder due to a chromosomal abnormality. It occurs once in every 900 births in the United States. The risk of Down syndrome increases with the age of the mother.
age 25: 1 in 1,250 births
age 30: 1 in 952 births
age 35: 1 in 378 births
age 40: 1 in 106 births
age 45: 1 in 30 births
Turner's syndrome: 1 in 5,000 births
Klinefelter's syndrome: 1 in 700 male births
Cri-du-chat: 1 in 20,000 births
Multifactorial inheritance disorders

Neural tube defects: 1 to 2 in 1,000 births
Anencephaly: 1 in 8,000 births
Spina bifida: 1 in 2,000 births
Congenital heart disorder: 1 in 115 births
Clubfoot: 1 in 735 births
Cleft lip/palate: 1 in 930 births

Diagnosis
Prenatal genetic screening has become a routine part of prenatal care. Important elements of screening include family history, the medical history of the parents and any history of exposure to environmental factors. In some cases, testing of one or both parents for a genetic disorder is done before or during pregnancy. To help screen for birth defects in the fetus, your doctor may suggest one or more of the following tests during pregnancy:
maternal serum alpha-fetoprotein screening (MSAFP), a simple blood test that can help identify an increased risk of neural tube defects
triple screen (alpha fetoprotein, human chorionic gonatropin and unconjugated estril), a blood test done at about 16 weeks to screen for Down syndrome
amniocentesis, a procedure in which amniotic fluid (the fluid that surrounds and protects the fetus in the womb) is withdrawn for examination
chorionic villus sampling, a procedure in which a small amount of the chorionic villi (small projections of tissue that attach the membrane of the embryo to the wall of the uterus) is taken for examination
ultrasound, the use of sound waves to create an image of the fetus
In the first few days after delivery, your baby's blood will also be tested to screen for several specific genetic disorders, including PKU and hypothyroidism.

Advances in genetic screening and diagnosis are continually being made. Discuss with your doctor any tests that may be appropriate for you and your baby.


Prevention
Discuss with your doctor any concerns you have about genetic disorders before becoming pregnant. To help reduce the risk of genetic disorders, consider the following preventive measures:
Take a daily supplement of 0.4 milligrams of folic acid before you become pregnant and at least through the first trimester of pregnancy.
See your doctor early in your pregnancy and as often as recommended until delivery.
Eat a nutritious diet and maintain a normal body weight.
Avoid smoking cigarettes, using street drugs, and drinking alcohol.
Avoid taking prescription and over-the-counter medications and dietary supplements unless your doctor specifically recommends them.