Disorders with multifactorial inheritance

-  are more common than mendelian disorders.

-  result from the combined actions of environmental factors & 2 or more mutant genes having additive effects (i.e. the greater the number of inherited mutant genes, the more severe the phenotypic expression of the disease). The disease clinically manifests only when the combined influences of the genes & the environment cross a certain threshold. 

-  include such common diseases as:-

o  Diabetes mellitus,

o  Hypertension,

o   Ischemic heart disease, 

o  Gout,

o  Schizophrenia, 

o  Bipolar disorders,

o    Neural tube defects, 

o   Cleft lip/ cleft palate,

o  Pyloric stenosis,

o    Congenital heart disease, etc….

-  are characterized by the following features:-

1. The risk of expressing a multifactorial disorder partly depends on the number of inherited mutant genes.

Hence, if a patient has more severe expression of the disease, then his relatives have a greater risk of expressing the disease (because they have a higher chance inheriting a greater number of the mutant gene). In addition, the greater the number of affected relatives, the higher the risk for other relatives.

2. The risk of recurrence of the disorder is the same for all first degree relatives of the affected individual & this is in the range of 2-7%. First-degree relatives are parents, siblings, & offspring. Hence, if parents have had one affected child, then risk that the next child will be affected is between 2 & 7%. Similarly, there is the same chance that one of the parents will be affected.

3. The concordance rate for identical twins (i.e. the probability that both identical twins will be affected) is 20 – 40% but this is much greater than the concordance rate for non-identical twins.

4. The risk of recurrence of the phenotypic abnormality in subsequent pregnancies depends on the outcome in previous pregnancies. When one child is affected, the chance that the next child will be affected is 7%. When 2 children are affected, then the chance that the next child will be affected increases to 9%.

References

Bezabeh ,M. ; Tesfaye,A.; Ergicho, B.; Erke, M.; Mengistu, S. and Bedane,A.; Desta, A.(2004). General Pathology. Jimma University, Gondar University Haramaya University, Dedub University.