A firm diagnosis allows the genetics team to accurately assess the couple’s chances of recurrence.

By Helga V. Toriello, Ph.D.

While every expectant couple hopes their child will be healthy, approximately 3-4% of couples will have a a child with a serious birth defect or combination of birth defects, called a syndrome, and another 1-3% will have a child with cognitive disabilities. Since prenatal testing is now readily available to parents, many will learn of a serious or life threatening problem during the pregnancy. When a child is born with a genetic condition or one is found prenatally, a referral to a genetics counselor may be made to provide the family with information regarding the diagnosis, prognosis and recurrence risks.

Genetic counseling is most accurate when the diagnosis is known as with chromosome anomalies (for example, Trisomy 21, Turner Syndrome and Trisomy 18) which are verified by blood tests or cleft/lip palate which is diagnosed by physical exam. In other instances, making a diagnosis is more complicated and may involve further prenatal testing such as DNA testing, detailed ultrasounds, echocardiograms or fetal blood sampling. Muscle or skin biopsies, X-rays, detailed physical exams with numerous measurements, and/or CT scans are often done on a child diagnosed at birth. A firm diagnosis allows the genetics team to accurately assess the couple’s chances of recurrence.

In general, there are four causes of birth defects and/or cognitive disability. Those include monogenic, chromosomal, multifactorial, or environmental. The following information is provided to allow parents to be better informed when seeking genetic counseling services:

Monogenic conditions

Monogenic conditions are those caused by changes in a gene or pair of genes. For every trait we have, a pair of genes interact to determine the trait. When the genes are the same (e.g., for blue eyes), the individual is homozygous for the trait. When the genes are different (e.g., one for brown eyes and one for blue eyes), the individual is heterozygous for the trait. In a heterozygote, one gene will exert a stronger effect than the other gene and is said to be dominant. In the example above, the brown eye gene is dominant over the blue eye gene, so the person will have brown eyes. When a child is born with a condition caused by the dominant gene (for example, neurofibromatosis or achondroplasia), either the child inherited the gene from one of the parents, or the gene “changed” in the egg or sperm that was involved in the child’s conception. When the gene is inherited from a parent, recurrence for those parents in future pregnancies is 50%, meaning that statistically half of future pregnancies will be affected and half will not. When the gene “changed,” recurrence is less than 1%. In either case, the chance of each of the affected child’s children having the condition is 50%.

Recessive conditions

On the other hand, when a child has a recessive condition (such as cystic fibrosis or albinism), that child is homozygous for the genes which cause the condition, having received one copy of the gene from each parent. The child then has two copies of the gene and thus has the condition. Recurrence risks for these parents in future pregnancies would be 25%.

X-linked conditions

Finally, some conditions such as Duchenne muscular dystrophy and hemophilia A, are X-linked; meaning the gene is positioned on the X chromosome, which is one of two sex chromosomes. Females have two X chromosomes, so they do not express the trait. However, males have only one X chromosome, so that every gene on that chromosome is expressed, including the hemophilia or Duchenne’s gene. If males have an X chromosome with a gene for a genetic condition, then unlike females, they will have the condition.

Chromosomal conditions

Chromosomal conditions are those caused by a change in the amount of chromosomal material and therefore involves several genes. If a child has an entire extra chromosome, he or she has trisomy (meaning three) of that chromosome. For example, Down syndrome is also called Trisomy 21 since there are three copies of the 21st chromosome instead of the usual two copies. For most parents of a baby with trisomy, recurrence risks are usually less than 1%. If only part of the a chromosome is extra or missing (a duplication or deletion), recurrence risks depend on whether one of the parents carries the chromosomal rearrangement which predisposed the egg or sperm to having too much or too little material. It is noteworthy that many conditions which formerly were of “unknown cause” have since been found to result from small chromosome deletions. One example is Prader-Willi Syndrome, which is usually caused by a small deletion in a segment of chromosome 14.

Multifactorial conditions

When a condition is said to be multifactorial, many factors are involved. It is usually considered to be an interaction between genes and environment, but it can also be an interaction just between genes. Most single birth defects (e.g., heart defects, spina bifida, and hip dislocation) are considered to be caused by multifactorial interaction. As a result, recurrence risks are usually between 2-5%. These risks are greater than for the general population, but lower than in instances of monogenic inheritance. However, all single birth defects can be part of a syndrome, and therefore counseling would depend on a detailed examination for the absence or presence of a syndrome.

Environmental factors

Finally, environmental factors may cause birth defects and/or cognitive disability. Although women are often concerned about different exposures they may have had during pregnancy, most medications and environmental exposures are not known to be harmful to the fetus. However, among those which may be harmful are alcohol, some seizure medications, accutane, cocaine and other “recreational” drugs and therapeutic (not diagnostic) levels of radiation. Recurrence risks depend on exposures in future pregnancies.

But what if a diagnosis cannot be made?

Unfortunately, a clear diagnosis can be hard to make. This is especially true when an autopsy is not performed after an unsuccessful pregnancy. Although the possibility exists that the condition could be genetic, in general, studies have shown that if no diagnosis is made and a child has a non-chromosomal condition, recurrence risks are 3-5%. This means that there is a 95-97% chance that it will not affect future children. In the vast majority of cases when clear recurrence risks can be given, the chances of a birth defect or genetic condition not happening again are far greater than the risk of recurrence. However, we must be mindful of the meaning of numbers to people who have already been affected by the devastation of learning of a genetic condition in a baby or unborn child. As is stated by the author of Another Letter to a Genetic Counselor, the idea of a few percent just wasn’t meaningful.

If you have questions about genetic counseling and genetic services, please call your local genetic clinic, March of Dimes office or contact the National Society of Genetic Counselors at 233 Canterbury Drive, Wallingford, PA 19806-6617, 610-872-7608.

Helga V. Toriello, Ph.D. is the Director of Genetic Services – Butterworth Hospital, Grand Rapids, Michigan. She is the co-author with Robert Gorlin, DDS, of Hereditary Hearing Loss and Its Syndromes. In addition, she is on the editorial boards of the Birth Defects Encyclopedia as well as numerous genetics journals.

Reprinted With Permission From Molly Minnick’s AHC newsletter. ©Copyright Pineapple Press.