Genetics Northern California

Multifactorial Inheritance

Multifactorial inheritance is the term used to describe the interplay of genetic and environmental factors. Multifactorial conditions do not follow an easily recognized pattern of inheritance.

Many common human diseases, such as cancer, heart disease, and diabetes are influenced by a person’s genetic make-up. However, instead of a single gene causing the disease, these diseases are usually due to the effect of multiple genes over the course of a lifetime. These genes interact with the environment to affect expression of the disease or human trait in question.

Examples of multifactorial conditions that are present at birth include cleft lip and palate, pyloric stenosis, hip dislocations, heart defects and spina bifida.

Hereditary risk
The chance for a multifactorial condition to happen more than once in the same family is estimated by studying many families from large populations. This is also called an “empiric risk”. Generally speaking, empiric risks are an average that will vary from family to family. The risk is dependent upon several factors. These include the relationship to the affected person, the total number of affected individuals in a family, the sex of the affected individual, and the severity of the disease.

Relationships in families are referred to as "degree of relationship" by geneticists. A direct relative (your parent, brother, sister, or child) is called a first degree relative. A person immediately connected to your direct relative (your grandparent, aunt, uncle, nephew or neice) is called a second degree relative. The degree of relatedness is important in determining risk to future pregnancies. The chance for another person in the family to have a multifactorial conditions is greatest for first degree relatives. For example, parents who have one child with a cleft lip have a 3-5% risk of having another affected child. More distant relatives, however, have a lower recurrence risk. A person whose uncle was born with a cleft lip has much less than a 1% risk for a similar birth defect in their child.

The number of affected individuals in a family is also important in determining risk. For example, if a couple has two children with a multifactorial condition such as a congenital heart defect (CHD), their subsequent children would be at greater risk than if the couple only had one child with a CHD.

The gender of the affected individual can sometimes be a factor in determining risk of recurrence. In some conditions, one gender may be more likely to be affected. For example, pyloric stenosis is a multifactorial disorder that occurs five times more frequently in males than in females. When it happens in a female, it suggests a greater genetic liability; presumably more abnormal genes are segregating in the family. So. if a female child has pyloric stenosis, her risk and her parent's risk of having another affected child would be higher than the risks for a male child with the same condition.

The degree of severity is important, too. The more severe the problem, the greater the likelihood for stronger genetic risks. For example, when a baby is born with a bilateral cleft lip (meaning both sides of the lip are involved), any future brothers and sisters are at higher risk than if the cleft lip was unilateral (only on one side).

Prevention of Multifactorial Diseases
At this point in time, there is no way to prevent a multifactorial disease from occurring in a newborn. However, there is substantial evidence that the vitamin folic acid reduces the incidence of one multifactorial birth defect: neural tube defects (including spina bifida). Taking folic acid during pregnancy may also reduce the chance for heart defects and facial clefts. Although folic acid doesn't change the genetic factors involved with these conditions, it appears to be an important enviromental factor.