Table of Contents- Lesson 1) ( Next) (Glossary)

MULTIFACTORIAL INHERITANCE

The most common cause of genetic disorders is multifactorial or polygenic inheritance. Traits that are due to the combined effects of multiple genes are polygenic (many genes). When environmental factors also play a role in the development of a trait, the term multifactorial is used to refer to the additive effects of many genetic and environmental factors. Expression of these traits may follow a normal, or "bell-shaped," curve. Examples of multifactorial traits include cleft lip and palate, congenital hip dislocation, schizophrenia, diabetes and neural tube defects such as spina bifida.

Multifactorial conditions tend to run in families, but the pattern of inheritance is not as predictable as with single gene disorders. The chance of recurrence is also less than the risk for single gene disorders. The degree of risk of a multifactorial disorder occurring in relatives is related to the number of genes they share in common with the affected individual. The closer the degree of relationship, the more genes in common. The degree of risk also increases with the degree of severity of the disorder.

Although multifactorial conditions run in families, the risk is generally less than the 25% or 50% seen in Mendelian conditions. Identical twins who are exactly alike genetically, do not always have the same condition when inheritance is multifactorial. This indicates that there are nongenetic factors that also play a role in the expression of multifactorial traits. For instance, the risk of coronary heart disease increases with smoking or obesity. The risk of emphysema in individuals with alpha-1-antitrypsin deficiency increases greatly with smoking. Maternal ingestion of valproic acid, a medication for seizures, increases the risk of spina bifida. Maternal alcohol abuse or uncontrolled diabetes increases the risk of having a child with a congenital heart defect.

Empiric risks are used to predict the recurrence of a multifactorial disorder. This is a risk that is based on epidemiologic and population studies and on mathematical models.

For many multifactorial or polygenic disorders, parents who have had one affected child have a 3-5% risk in future pregnancies of having another affected child. Affected individuals have a similar risk in future progeny. More distant relatives, however, have a lower recurrence risk.

In conditions inherited in a multifactorial fashion, the risk may depend on the sex of the affected individual. For example, pyloric stenosis is a multifactorial disorder that occurs five times more frequently in males than in females. If a female child has pyloric stenosis, her risk and her parent's risk of having another affected child would be higher than if a male child has pyloric stenosis. Occurrence in a female suggests a greater genetic liability; presumably more abnormal genes are segregating in the family.

SUMMARY

Key points to remember about multifactorial inheritance:

Some of the most common chronic diseases are multifactorial genetic disorders. Conditions with multifactorial inheritance include many birth defects, cancers, coronary artery disease, diabetes, hypertension, and mental disorders. It explains the familial distribution of many disorders. In general, the recurrence risk is based on experience and on observation of these disorders in the general population.

Table of Contents- Lesson 1) (Next) (Glossary)