Multifactorial Inheritance and Birth Defects

Multifactorial inheritance means that many factors are involved in causing a birth defect. The factors are usually both genetic and environmental, where a combination of genes from both parents, in addition to unknown environmental factors, produce the trait or condition. Often one gender (either males or females) is affected more frequently than the other in multifactorial traits.

Multifactorial traits do recur in families, because they are partly caused by genes. The chance for a multifactorial trait or condition to happen again depends upon how closely the family member with the trait is related to you. For example, the risk is higher if your brother or sister has the trait or disease, than if your first cousin has the trait or disease. Family members share a certain percentage of genes in common, depending upon their relationship. For example:

Examples of multifactorial traits and diseases include: height, neural tube defects, and hip dysplasia.

Height

Height is determined by both genetic and environmental factors. Some people may be exceptionally short or exceptionally tall, often due to some gene with a major effect on height. Otherwise, children are often a height similar to, or "in-between" their parents, or simply closer to the population average.

Neural tube defects

Neural tube defects, spina bifida (open spine), and anencephaly (open skull), are seen in one in every 1,500 live births per year. During pregnancy, the human brain and spine begin as a flat plate of cells, which rolls into a tube, called the neural tube. If all or part of the neural tube fails to close, leaving an opening, this is known as an open neural tube defect, or ONTD. This opening may be left exposed, or covered with bone or skin.

Anencephaly and spina bifida are the most common ONTDs, while encephaloceles (where the brain or its coverings protrude through the skull) are much rarer. Anencephaly occurs when the neural tube fails to close at the base of the skull, whereas spina bifida occurs when the neural tube fails to close somewhere along the spine. Babies with anencephaly are stillborn or usually live for a very short time after delivery. Babies born with spina bifida may have minor or temporary problems, or may have permanent, often serious, physical problems. These may include paralysis, lack of bowel and bladder control, club feet, hydrocephaly (a buildup of spinal fluid in the head), and intellectual disability. In most cases, one or more surgeries after birth may be needed.

ONTDs occur in children without a prior family history of these defects in most cases. ONTDs result from a combination of genes inherited from both parents, coupled with environmental factors. Some of the environmental factors include uncontrolled diabetes in the mother, and use of certain prescriptions medications. ONTDs are seen five times more often in females than males. Once a child has been born with an ONTD in the family, the chance for an ONTD to happen again in a future pregnancy is increased. It is important to understand that the type of neural tube defect can differ the second time. For example, one child could be born with anencephaly, while the second child could have spina bifida.

The neural tube closes 28 to 32 days after conception, before many women are aware they are pregnant. Folic acid is a B vitamin reduce the chance for neural tube defects. For this reason, experts recommend all women in their reproductive years take a multivitamin containing folic acid. However, do not take more than one multivitamin per day.

If a couple has had a previous child with an ONTD, a larger amount of folic acid is recommended. The CDC recommends that a woman take 4.0 mg (4,000 mcg) of folic acid one month before becoming pregnant (before conception). To obtain this amount of folic acid, you must get a prescription from your healthcare provider.

ONTDs can be diagnosed before birth by measuring a protein called AFP (alpha-fetoprotein) present in the amniotic fluid around the baby. Fetal ultrasound during pregnancy can also give information about the possibility of an ONTD, but is not always accurate, since some babies with an ONTD may look the same on ultrasound as those without these defects. Measurement of the AFP, and other biochemical markers from amniotic fluid, is over very accurate for detecting ONTDs. Small or closed defects (which do not leak spinal fluid) may not be picked up by this test.

For all women who are pregnant who have not previously had a child with an ONTD and do not have a family history of ONTDs, the American College of Obstetrics and Gynecology (ACOG) recommends that a blood test be offered between 15 to 20 weeks, to measure AFP (and other biochemical markers) to determine whether a pregnancy is at increased risk for an ONTD. Although this test (sometimes called maternal serum screening, the double screen, triple, or quadruple screen) does not tell a couple for certain whether their baby has an ONTD, it will determine which pregnancies are at greater risk, so that additional testing will be offered.

Hip dysplasia

One of the environmental influences thought to contribute to hip dysplasia is the baby's response to the mother's hormones during pregnancy. The overall occurrence of hip dysplasia is about one in 1,000 live births.