(Table of Contents-Lesson 2) , (Next) (Glossary)

When people hear the word "genetics" they often think of pregnant women, children with birth defects, and childbearing couples. This term rarely conjures up thoughts of healthy adolescents or adults. Therefore, you may not readily recognize everyone who might benefit from a genetic consultation.

While there are no established criteria for the types of patients that merit genetic consultation, there are some general rules you can use. The following is a list of reasons for referral. This list has been divided into the different stages in the life cycle.

PRECONCEPTION

Prior to conception there are a number of factors that might lead you to conclude a woman/couple could benefit from a consultation. The reasons for referral include the following:

• A positive family history of a genetic disorder (e.g., fragile X syndrome, muscular dystrophy, cystic fibrosis) and concern about recurrence
• Members of a high-risk ethnic group
• Previous infertility or sterility problem
• Exposure to potential teratogenic or mutagenic agents
• Maternal health (e.g., diabetes, PKU, epilepsy)
• Consanguineous marriage
• Anxieties over childbearing
• Two or more prior miscarriages or pregnancy losses
• A previous stillborn child
• A previous child with a genetic or chromosomal disorder or birth defect (e.g., neural tube defect, Down syndrome, PKU)

The goal of preconception counseling is to provide couples with the information necessary to make informed decisions about reproduction and the available testing, intervention or treatment options. Members of high-risk ethnic groups, for instance, should be told that carrier testing is available. Individuals who carry a balanced chromosome rearrangement should be offered the option of prenatal diagnosis in future pregnancies, and women who are using teratogenic agents should be counseled about the associated risks.

The advantage of preconception counseling is that it is possible to pursue genetic studies prior to pregnancy. In the absence of time constraints, a tiered evaluation can be done. Medical records can be requested and reviewed, laboratory tests can be ordered and analyzed systematically, and extended family studies can be undertaken as needed.

Other reasons to pursue genetic studies prior to conception include the fact that some test results are unreliable during pregnancy (e.g., hexosaminidase enzyme levels in pregnant women who carry the gene for Tay-Sachs disease). Certain prevention strategies may only be effective if instigated prior to conception. For instance, all women of childbearing age should take 0.4 mg of folic acid daily to decrease the risk of having a child with a neural tube defect. Women who have had an affected child should take 4 mg of folic acid daily for three months prior to conception. This has been shown to significantly decrease the recurrence of NTDs in subsequent pregnancies.

Women with health problems are more likely to have babies with birth defects. For example, babies born to insulin dependent diabetic women are more likely to have congenital heart defects, genitourinary defects, and caudal regression sequence, unless the diabetes is strictly controlled prior to conception and during the first trimester. Mothers with PKU need to have normalized levels of phenylalanine prior to conception to prevent mental retardation in the child. Women on anticonvulsant medication should be switched to the least teratogenic drug, and the smallest clinically effective dose.

PRENATAL

During pregnancy, there are tests that can be done to determine whether or not the fetus has a chromosome abnormality, certain single gene disorders or structural abnormalities. Women who might benefit from prenatal diagnostic tests and counseling include the following:

• Women who will be 35 years old or older at delivery
• A woman and/or her partner who are known to carry genes coding for a genetic disorder
• A woman or her partner who are known to carry a chromosome rearrangement or abnormality
• Couples with a family history of a neural tube defect
• Couples with a previous child born with multiple congenital anomalies or a chromosome abnormality
• Women with an abnormal level of maternal serum alpha fetoprotein (AFP), human chorionic gonadotrophin (hCG), or estriol (uE3)
• Women exposed to an infectious disease, radiation, drugs or other environmental agents during pregnancy

Due to the increased risk of chromosome abnormalities in babies born to women over the age of 34, the American College of Obstetricians and Gynecologists recommends that all pregnant women who will be 35 years or older at delivery should be offered the option of prenatal diagnosis. The College also recommends that a maternal serum marker screen be offered to all pregnant women between 15 and 18 weeks gestation.

Many single gene disorders can be diagnosed prenatally. As the technology is changing rapidly, if the patient or her partner has a single gene disorder or if they have a child with a recessive genetic condition, it is important to determine if new prenatal tests have been developed since the last pregnancy.

Women who are exposed to teratogenic agents during pregnancy may also benefit from genetic counseling. In some instances the risk of an abnormality may be much lower than first assumed and counseling may reduce maternal anxiety. In some cases, further diagnostic studies may be proposed to assess fetal development or to rule out the presence of obvious structural defects associated with exposure to a specific agent. Only rarely are the risks of a birth defect high enough to make pregnancy termination a reasonable option.

INFANCY AND CHILDHOOD

Factors that might lead you to conclude that an infant or child might benefit from a genetic evaluation include the following:

• A history of intrauterine growth retardation or failure to thrive
• Abnormal growth patterns (short stature, obesity, excessive growth)
• Ambiguous or abnormal genitalia, early onset of puberty
• Microcephaly, macrocephaly or craniosynostosis
• Psychomotor delay or mental retardation
• Hypotonia, hypertonia
• A parent, sib or other relative who has problems similar to those observed in the patient
• Abnormal or unusual facial features
• Abnormal body and limb proportions, asymmetry
• Major or minor congenital anomalies
• Metabolic disorder
• Muscular weakness
• Bleeding tendency
• Blindness or deafness
• A significant regression in developmental progress
• An unusual body odor
• Excessive unexplained vomiting
• Unusual behaviors, especially when associated with minor malformations (hand biting, hand flapping, autistic symptoms, abnormal sleep patterns, etc.)

Major malformations are often noted at delivery or shortly after birth, and a genetic consultation is usually requested prior to discharge from the hospital. In some cases, establishing a diagnosis in the newborn period may be critical if informed decisions are to be made about surgery or the degree of medical intervention provided to sick babies. In infants with ambiguous genitalia, for example, it is important to establish the chromosomal sex and rule out the diagnosis of congenital adrenal hyperplasia (CAH); as infants with CAH may experience a life threatening deficiency of cortisone under stress.

While major malformations are often diagnosed prior to discharge, some problems emerge over time. Changes in the normal patterns of growth and development may be the first clue that a child has an underlying genetic disorder. Changes in a child's health and capabilities is another reason for referral. Some inborn errors of metabolism, for example, are accompanied by acute encephalopathy, lethargy, hypertonia or hypotonia, and seizures caused by the toxic effects of metabolites on the brain. Other inborn errors of metabolism may cause progressive encephalopathy later in infancy or childhood with gradual spasticity or ataxia, dementia, visual or hearing loss, and enlargement or abnormal function of organs such as the liver, heart, kidneys, and joints.

ADOLESCENCE AND ADULTHOOD

Some reasons for adolescent and adult referrals for a genetic evaluation and counseling are listed below:

• Abnormal sexual maturation
• Amenorrhea (failure to menstruate), delayed puberty
• Growth retardation
• Excessive tall stature
• A diagnosis of an adult onset genetic disease (e.g., Huntington disease, Marfan syndrome, myotonic dystrophy)
• A positive history of familial disorders (e.g., colon cancer, breast/ovarian cancer, familial hypercholesterolemia, psychiatric or behavioral disorders)
• Members of high-risk groups who want to pursue carrier testing for single gene disorders or chromosome abnormalities (e.g., Tay-Sachs disease, Duchenne muscular dystrophy, hemophilia, sickle cell anemia, translocation carrier)
• Paternity testing
• Questions about genetic diseases or birth defects in immediate or extended family members

Changes in the normal patterns of sexual development or growth during the teen years should prompt a genetics referral. The option of carrier testing should be offered to individuals belonging to high-risk groups. Individuals diagnosed with an adult onset genetic condition should be referred to discuss the genetics of their condition and the risk to other family members. Risk assessment programs are available in most areas for people with a family history of certain types of cancer and other genetic conditions.

If you are uncertain about the available services or you have questions about a particular patient, contact the genetics program in your area (Appendix E).

Lesson 2-Table of Contents) (Next) (Glossary)