The pregnancy history may reveal a specific non-genetic cause, such as maternal illness due to infection or drug therapy or misuse. An abnormal fetal intra-uterine position may suggest a mechanical uterine factor causing deformation or disruption. Pre-existing risk factors may be suggested from parental ages, occupations, past medical and drug history.

Single congenital malformations

Environmental factors (such as drugs and infections) may be wholly or partly responsible for some malformations (see table 7). As not all embryos subjected to a particular environmental factor develop a malformation, it is assumed that those who are affected may have a genetic predisposition. The combination of genetic and environmental influences form the basis of the multifactorial model (which will be discussed in the Paediatrics module).

Neural tube defects are an excellent example of how the environmental component can be modified by maternal treatment with folic acid resulting in a fall in the rate of recurrence in susceptible individuals by one half.

Recurrence risks are generally between 1-5% depending on the genetic component and have to be determined by empiric population studies.

Multiple malformation syndromes

Multiple malformation syndromes may be due to chromosomal imbalance, single gene mutations, teratogens or unknown factors.

Malformation sequence

The recurrence risk is that associated with the cause of the single malformation which led to the sequence.

Association

As, by definition, the cause of an association is unknown, recurrence risks have to be determined by empiric family studies - by direct observation of the recurrence risk.