Genetics

PND's are genetic diseases.

Each specific PND has its own variation (an unusual form) mutation (alteration) of a gene. For genetic information about specific PND's please refer to the PND's defined link under "what causes" or under genetics " disease specific".

The following information is provided to help you to understand what having a genetic disease means for your child, yourself, other children and family members. It is not intended to, nor does it constitute medical or other advice. For more information about patterns of inheritance and genetic testing consultation with an ABMG (American Board of Medical Genetics) board certified clinician or clinical biochemical geneticist is recommended.

Having a child or a family member with a genetic disease might also spark many questions about the risk of having other children, what are the options, what should we do? To assist with the decision making process one should consider a visit with a genetic professional.

The information below can be found on the Genetics Home Reference page www.ghr.nlm.nih.gov

The Genetics Home Reference is the National Library of Medicine's web site for consumer information about genetic conditions and the genes or chromosomes responsible for those conditions.

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional.

What is a gene?

A gene is the basic physical and functional unit of heredity. Genes, which are made up of DNA, act as instructions to make molecules called proteins. In humans, genes vary in size from a few hundred DNA bases to more than 2 million bases. The Human Genome Project has estimated that humans have between 20,000 and 25,000 genes.

Every person has two copies of each gene, one inherited from each parent. Most genes are the same in all people, but a small number of genes (less than 1 percent of the total) are slightly different between people. Alleles are forms of the same gene with small differences in their sequence of DNA bases. These small differences contribute to each person's unique physical features.

What are genetic disorders?

A genetic disorder is a disease caused in whole or in part by a "variation" (an unusual form) or "mutation" (alteration) of a gene. Genetic disorders can be passed on to family members who inherit the genetic abnormality. A small number of rare disorders are caused by a mistake in a single gene. But most disorders involving genetic factors - such as heart disease and most cancers - arise from a complex interplay of multiple genetic changes and environmental influences.

Geneticists group genetic disorders into three categories:

Single gene disorders caused by a mistake in a single gene. The mutation may be present on one or both chromosomes of a pair. Sickle cell disease, cystic fibrosis and Tay-Sachs disease are examples of single gene disorders.

Chromosome disorders caused by an excess or deficiency of the genes. For example, Down syndrome is caused by an extra copy of a chromosome, but no individual gene on the chromosome is abnormal.

Multifactorial inheritance disorders caused by a combination of small variations in genes, often in concert with environmental factors. Heart disease, most cancers and Alzheimer's disease are examples of these disorders.

Genetic Inheritance

What is an autosomal recessive pattern of inheritance?

In an autosomal recessive pattern of inheritance the condition does not occur unless an individual inherits the same defective gene for the same trait from each parent. A child who receives one normal gene and one gene for the disease will be a carrier but usually will not show symptoms. The risk of transmitting the disease to the children of a couple, both of whom are carriers for a recessive disorder, is 25 percent. 50 percent of their children risk being carriers of the disease but generally will show no symptoms of the disorder, 25 percent of their children may receive both normal genes, one from each parent, and will be genetically normal for that trait. The risk is the same for each pregnancy.

What is an autosomal dominant pattern of inheritance?

In an autosomal dominant pattern of inheritance an affected person usually has unaffected parents who each carry a single copy of the mutated gene (and are referred to as carriers). In autosomal dominant disorders if one parent has an abnormal gene and the other parent a normal gene, there is a 50 percent chance each child will inherit the abnormal gene, and therefore the dominant trait. This does not mean that children WILL necessarily be affected. It does mean that EACH child has a 50:50 chance of inheriting the disorder. Children who do not inherit the abnormal gene will not develop or pass on the disease.

What is genetic testing?

Genetic tests look for abnormalities in a person's genes, or the presence/absence of key proteins whose production is directed by specific genes. Abnormalities in either could indicate an inherited disposition to a disorder. Genetic testing includes gene tests (DNA testing) and biochemical tests (protein testing).

In gene tests, DNA in cells taken from a person's blood, body fluids or tissues is examined for an abnormality that flags a disease or disorder. The abnormality can be relatively large - a piece of a chromosome, or even an entire chromosome, missing or added. Sometimes the change is very
small - as little as one extra, missing or altered chemical base within the DNA strand. Genes can be amplified (too many copies), over-expressed (too active), inactivated, or lost altogether. Sometimes pieces of chromosomes become switched, transposed or discovered in an incorrect location.

Gene tests use a variety of techniques to examine a person's DNA. Some tests involve using probes - short strings of DNA - with base sequences complementary to those of the mutated gene. These probes will seek their complements within an individual's genome. If the mutated sequence is present in the patient's genome, the probe will find it and bind to it, flagging the mutation.

Another type of gene tests involves comparing the sequence of DNA bases in a patient's gene to a normal version of the gene.

Biochemical tests look for the presence or absence of key proteins which signal abnormal or malfunctioning genes.

What information can genetic testing provide?

Genetic testing can be predictive, discovering whether an individual has an inherited disposition to a certain disease, before symptoms appear. Genetic tests can also confirm a diagnosis if symptoms are present. Tests can determine whether a person is a carrier for the disease. Carriers won't get the disease, but can pass on the faulty gene to their children. Prenatal testing can help expectant parents know whether their unborn child will have a genetic disease or disorder. Newborn screening tests infants for abnormal or missing gene products.

Individuals in families at high risk for a disease live with troubling uncertainties about their own future as well as their children. A negative test - especially one that is strongly predictive - can provide an enormous sense of relief.

A positive test can also produce benefits. In the best circumstances, a positive test enables the person to take steps to reduce risk. These steps could include regular screening for the disease or lifestyle changes, such as a change in diet or regular exercise. A positive test can relieve uncertainty, and can enable people to make informed decisions about their future.

Reasons for Genetic Testing

Predictive testing identifies people who are at risk of getting a disease before any symptoms appear. Predictive tests include those that screen for some inherited predispositions to certain forms of cancer, such as colon and breast cancer. Being predisposed does not mean that the individual will get the disease. It means the person has a certain risk of developing the disease.

Carrier testing can tell individuals if they are carriers of an inherited disorder that they may pass on to their children. A person who has only one abnormal copy of a gene for a recessive condition is known as a carrier. Carriers won't get the disease, but can pass on the defective gene to their children. Cystic fibrosis and Tay-Sachs disease are examples of disorders for which parents can be carriers.

Prenatal testing is available to people at risk for having children with a chromosomal abnormality or an inherited genetic condition. Two procedures are commonly used in prenatal testing. Amniocentesis involves analyzing a sample of amniotic fluid from the womb. CVS (chorionic villus sampling) involves taking a tiny tissue sample from outside the sac where the fetus develops. Prenatal testing is often used to look for disorders such as Down syndrome, spina bifida, cystic fibrosis, and Tay-Sachs disease.

Newborn screening, the most widespread type of genetic testing, tests infant blood samples for abnormal or missing gene products. For example, infants are commonly screened for Phenylketonuria (PKU), an enzyme deficiency that can lead to severe mental retardation if untreated.

How should I decide whether to be tested?

The decision to undergo testing is a very personal one. For many people, a pivotal consideration is whether there are preventive measures that can be taken if the test result is positive. For example, those who test positive for inherited forms of breast or colon cancer can benefit from preventive measures, screening for early detection, and early treatment.

In contrast, there are no preventive measures or cures for Huntington's disease. But a positive test for Huntington's disease might help an individual make lifestyle decisions, such as career choice, family planning or insurance coverage.

Because the decision about whether to be tested for a genetic disease is complex, most people seek guidance from a genetic counselor (see below) trained to help individuals and families weigh the scientific, emotional and ethical considerations that impact on this decision.

Newborn screening

A test that uses a few drops of blood can detect medical problems early in a baby's life.

Newborn screening is the practice of testing all babies for rare disorders that can hinder their normal development. These disorders are not apparent at birth but develop later in infancy or childhood. Newborn screening helps to detect problems early in a baby's life, allowing treatment that may prevent mental retardation, physical disability, or life-threatening illnesses.

Testing usually occurs 24 to 48 hours after the baby is born. The test is performed by pricking the baby's heel to collect a few drops of blood. The blood is placed on a special piece of paper and sent to a laboratory for analysis. Parents can ask for a copy of the test results, which are sent to the baby's doctor or clinic. Sometimes a repeat test is required, particularly if the first test was done before the baby was 24 hours old. Because screening indicates only the possibility that an infant may have a particular disorder, additional testing is required to confirm abnormal screening results. If retesting is necessary, parents are notified within a few days of the initial test.

Although all states and the District of Columbia provide newborn screening, testing varies from state to state. Some states test for fewer than 10 disorders, while others test for 30 or more. To make testing more uniform and comprehensive, the Health Resources and Services Administration (HRSA) issued a draft report that recommends screening for certain disorders. This report also recommends a test for hearing loss in newborns. The hearing test uses a small, soft microphone or earphone that is placed in the baby's ear. Parents can ask for expanded (or supplemental) screening if they live in a state that tests for a limited number of disorders.

Please use the links below to learn more about newborn screening.

Newborn Screening: Past, Present, and Future(Nemours Foundation)

Newborn screening resources (U.S. National Library of Medicine)

Description of disorders detected through newborn screening (Genetics Home Reference)

Current screening by U.S. state (National Newborn Screening and Genetics Resource Center)

The HRSA report on newborn screening (Maternal and Child Health Bureau, HRSA)

Supplemental screening (Save Babies Through Screening Foundation)

These tests could save your baby's life (Maternal and Child Health Bureau, HRSA)

Has your baby's hearing been screened? (National Institute of Deafness and Other Communication Disorders)