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