**3. Congenital anomalies in monogenic diseases**

Very often, genetic congenital anomalies are part of the clinical presentation of monogenic diseases; 7.5% of isolated or syndromic congenital anomalies are caused by monogenic disorders. Congenital anomalies can become obvious prenatally or at birth, and at times, they are noticeable only in later development, but in all cases, it happens between conception and birth.

The diagnosis of a monogenic disease is often established based on a conclusive family history, clinical examination, and pedigree pattern and confirmed through genetic testing.

With a known diagnosis, the risk of recurrence will be estimated according to the inheritance pattern of the disease. When definite diagnosis is not available, all attempts should be made to associate the clinical picture with a specific disease. If successful, precise genetic counseling can be offered. Situations when diagnosis cannot be demonstrated before birth are difficult to manage—the counselor will advise the couple when there is a lack of crucial medical information.

Should screening identify congenital anomalies during intrauterine life, couples will be faced with a pressing situation, as anomaly finding does not necessarily imply certain diagnosis. In this case, establishing the diagnosis should be aimed for whenever possible, as the first step in genetic counseling.

There are situations with a known diagnosis and known disease-causing mutation that allow prenatal diagnosis testing. Prenatal invasive diagnosis for monogenic disease running in the family, depending on its severity, should and will be recommended. If diagnosis can be readily established, then the recurrence risk can be calculated. Probability of inheritance based on Mendel's principles and conditional probability (also known as Bayesian analysis, based on Bayes' theorem on probability) are used to calculate genetic risk [1].

The risk of expressing a monogenic disease is dependent not only on the pattern of inheritance, but also on other factors such as the incidence of the disease, the presence of other affected members, the penetrance and variable expressivity, ethnicity, and the influence of environmental factors.
