Pediatric Annals

GENETIC SCREENING 

Resident's Column

Cheryl Garganta, MD, PhD; Joachim Kapalanga, MD

Abstract

In the futuristic movie Gattaca, a child is born after being conceived without the help of the local geneticist. A few minutes after birth, a blood test determines his risk for various conditions, including a high risk for premature death due to heart problems. As the Human Genome Project nears completion, there are undoubtedly some individuals who feel that genetic screening like that in Gattaca will soon be available.

In this issue of Pediatric Annals, genetic screening, the ultimate spin-off from the Human Genome Project, is addressed. Fortunately or unfortunately, our current use of genetic screening is nowhere near as inclusive as that in Gattaca. In fact, most of the genetic screening discussed in this issue does not identify genotype at all. The only exceptions are newborn screening for hemoglobinopathies, where the genotype is implied by the screening result, and cystic fibrosis in screening programs that screen for AF508 as a second stage screen. In most cases, it is more important to identify the phenotype (eg, phenylketonuria or biotinidase deficiency) than the specific mutation responsible for the condition.

As the articles in this issue reveal, genetic screening takes many forms, some of which we use more frequently than others. Family history is one of the first types of genetic screening we all learn, starting early in our medical school training. In some form, a family history is obtained for each new patient. When a new problem arises that might have a genetic source, the original family history may be amended with more specific information directed at identifying a possible etiology of that problem.

Because of their differing focuses, pediatricians and geneticists use family histories differently. Pediatricians tend to use family history to identify common conditions for which a patient may be at risk later in life, only occasionally using it to find the cause of a particular problem. Geneticist focus more on using the family history to provide clues to the diagnosis of a current problem and then secondarily to identify other, possibly genetic, conditions. It is the patient who benefits from the combination of these different approaches.

For many pediatricians, screening tests, often instituted by geneticists, result in more headaches than help. Newborn blood screening and hearing tests must be done before discharge from the hospital. Once the baby comes to the pediatric office, it is necessary to verify that the screening was done and that the results were normal. It is usually the pediatrician who has to explain to parents why their child needs additional testing and make arrangements for that testing. Only rarely does subsequent testing confirm the diagnosis.

As genetics residents, we have the advantage of seeing children with phenylketonuria and other metabolic diseases grow and develop normally. This helps balance the inconvenience of false-positive screens. It is hoped that the addition of newer testing methods such as tandem mass spectroscopy will decrease the false-positive rate in newborn blood screening tests, as well as parental anxiety. For some conditions, the combination of screening for biochemical markers followed by mutational analysis for common mutations may decrease the falsepositive rate even further.

As genetics residents, we see and use many different kinds of genetic screening. Premarital screening in the Orthodox Jewish community aims to decrease the number of couples at risk for having children with one of the devastating diseases that are more common in Ashkenazim. The triple screen and targeted ultrasounds done during pregnancy are used to identify women at higher risk for having a child with a neural tube defect or certain chromosome abnormalities. New tests continue to be added to the newborn blood screening tests,…

In the futuristic movie Gattaca, a child is born after being conceived without the help of the local geneticist. A few minutes after birth, a blood test determines his risk for various conditions, including a high risk for premature death due to heart problems. As the Human Genome Project nears completion, there are undoubtedly some individuals who feel that genetic screening like that in Gattaca will soon be available.

In this issue of Pediatric Annals, genetic screening, the ultimate spin-off from the Human Genome Project, is addressed. Fortunately or unfortunately, our current use of genetic screening is nowhere near as inclusive as that in Gattaca. In fact, most of the genetic screening discussed in this issue does not identify genotype at all. The only exceptions are newborn screening for hemoglobinopathies, where the genotype is implied by the screening result, and cystic fibrosis in screening programs that screen for AF508 as a second stage screen. In most cases, it is more important to identify the phenotype (eg, phenylketonuria or biotinidase deficiency) than the specific mutation responsible for the condition.

As the articles in this issue reveal, genetic screening takes many forms, some of which we use more frequently than others. Family history is one of the first types of genetic screening we all learn, starting early in our medical school training. In some form, a family history is obtained for each new patient. When a new problem arises that might have a genetic source, the original family history may be amended with more specific information directed at identifying a possible etiology of that problem.

Because of their differing focuses, pediatricians and geneticists use family histories differently. Pediatricians tend to use family history to identify common conditions for which a patient may be at risk later in life, only occasionally using it to find the cause of a particular problem. Geneticist focus more on using the family history to provide clues to the diagnosis of a current problem and then secondarily to identify other, possibly genetic, conditions. It is the patient who benefits from the combination of these different approaches.

For many pediatricians, screening tests, often instituted by geneticists, result in more headaches than help. Newborn blood screening and hearing tests must be done before discharge from the hospital. Once the baby comes to the pediatric office, it is necessary to verify that the screening was done and that the results were normal. It is usually the pediatrician who has to explain to parents why their child needs additional testing and make arrangements for that testing. Only rarely does subsequent testing confirm the diagnosis.

As genetics residents, we have the advantage of seeing children with phenylketonuria and other metabolic diseases grow and develop normally. This helps balance the inconvenience of false-positive screens. It is hoped that the addition of newer testing methods such as tandem mass spectroscopy will decrease the false-positive rate in newborn blood screening tests, as well as parental anxiety. For some conditions, the combination of screening for biochemical markers followed by mutational analysis for common mutations may decrease the falsepositive rate even further.

As genetics residents, we see and use many different kinds of genetic screening. Premarital screening in the Orthodox Jewish community aims to decrease the number of couples at risk for having children with one of the devastating diseases that are more common in Ashkenazim. The triple screen and targeted ultrasounds done during pregnancy are used to identify women at higher risk for having a child with a neural tube defect or certain chromosome abnormalities. New tests continue to be added to the newborn blood screening tests, and more hospitals are starting to screen for congenital hearing loss. Evaluation of the nondysmorphic child with developmental delay often starts with a series of screening tests such as chromosome analysis and Fragile X testing. There are also second level genetic screens. Once a child is diagnosed as having a particular condition, genetic testing may be done for common mutations associated with that condition. Understanding test characteristics such as specificity and sensitivity and factors that influence the test results is necessary for the effective use of these screening tests.

Although we may not be using genetic screening at the same level as in Gattaca, we seem to be getting a little closer every day. In the movie,, everyone had genetic screening without choice and the results of that screening were used to limit the lives of some individuals. It is hoped that we, as pediatricians and geneticists, will never allow this to happen. As long as the patient, the parents, or both are free to choose screening and understand the implications of the results, our recent rapid advances in genetic screening may be a good thing because they may help us take better care of our patients.

10.3928/0090-4481-20000501-10

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