Multifactorial Inheritance and Birth Defects

Multifactorial Inheritance

What is multifactorial inheritance?

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. There appears to be a different threshold of expression, which means that one gender is more likely to express the condition over the other gender. For example, hip dysplasia is nine times more common in females than males.

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:

Now, if we look at a multifactorial condition, such as a neural tube defect (NTD), the chance for this birth defect to be seen in a future pregnancy would be:

• 4 percent chance if one parent had a neural tube defect (NTD)

• 4 percent chance of recurrence if one child has NTD

• 10 percent chance of recurrence if two children have NTD

As you can see, the more genes you have in common with the family member, the higher the chance for you to have a child with a similar defect.

What are some of the different types of multifactorial traits and diseases?

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 (80 percent of the time), or covered with bone or skin (20 percent of the time). Anencephaly and spina bifida are the most common ONTDs, while encephaloceles (where there is a protrusion of the brain or its coverings 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 minimal or transient (temporary) problems, or may have permanent, often serious, physical problems. These may include paralysis, lack of bowel and bladder control, club feet, hydrocephaly (a condition marked by an accumulation of spinal fluid in the head), and mental retardation. In most cases, one or more surgeries after birth may be necessary. Some centers offer fetal surgery to attempt to close the defect prior to delivery. Once the diagnosis of an ONTD is made during a pregnancy, a medical center that specializes in the treatment and repair of ONTDs may be sought.

  ONTDs occur in children without a prior family history of these defects in over 90 percent of 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 medications that are available by prescription only. 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 to 4 percent. 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 and not anencephaly.

  The neural tube closes 28 to 32 days after conception, before many women are aware they are pregnant. Folic acid is a B vitamin found to reduce the chance for neural tube defects to occur. For this reason, the American College of Medical Genetics (ACMG) and the CDC recommend that 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 physician or 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 100 percent 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 95 percent 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. As mentioned, hip dysplasia is nine times more common in females than males. 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 one in 1,000 live births.