Inherited, genetic and congenital disorders

What’s the difference?

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Which is the difference between inherited, genetic and congenital disorders? We often hear about hereditary and/or genetic and/or congenital disorders. Unfortunately, these terms are often confused or, even worse, used interchangeably. A hereditary disorder is certainly genetic: indeed, it can be defined as a disease caused by a genetic mutation that has been transmitted from parents to the offspring. Instead, “congenital” refers to a disease present from birth. However, it is not certain that a congenital disorder is also genetic and that, if genetic, it is also hereditary or transmissible.

Genetic and not genetic

Therefore the primary classification is in hereditary diseases (all genetic) and congenital diseases (not all genetic). For example, malformation syndromes are congenital diseases because they are clinically evident from birth (and sometimes already in utero through ultrasound), but they are not always hereditary. Fetal malformations due to exposure to pollutants or so-called teratogenic drugs, for example, are non-hereditary congenital disorders. On the other hand, mucopolysaccharidosis, mucolipidosis, and syndromic diseases of metabolic origin are under the chapter of hereditary congenital disorders.

Not inherited and not transmissible genetic defects

There are also intermediate cases characterized by genetic defects which, due to their particular origin, it is not entirely appropriate to classify as hereditary. Classic example: de novo chromosomal disorders. Malformation syndromes of chromosomal origin are due to de novo chromosomal aberrations, i.e., absent in the parent, and caused by pre or post-zygotic chromosomal rearrangement events. Therefore, unless the chromosomal defect is present in a certain amount of sperm or egg cells of one parent (germinal mosaicism, which is impossible to exclude with certainty), it is improper to define these syndromes as hereditary. Furthermore, since, in many cases, these syndromes prevent the affected individual from reproducing, the disease is not transmissible.

De novo mutations

All the disorders caused by de novo genetic mutations (both chromosomal and genic) would deserve a deeper discussion. But, overall, de novo is used to label a mutation identified in the affected person and absent in both parents. This can have two causes: (1) the genetic defect is post-zygotic: the mutation arises during the first cell divisions after fecundation, and as such, it will be present only in some cells of the newborn. In this case, we talk about “somatic mutation.” (2) The genetic defect is pre-zygotic, present in one of the parents but only in some cells of the parental gonads. In this case, we talk about parental gonadal mosaicism in one of the parents.

Empirical risk

A parent with gonadal mosaicism will be completely asymptomatic (or only mildly affected if the mutation is also present in some body cells) and will have an empirical risk of retransmitting the mutation in subsequent conceptions. Such risk is estimated to be around 5%. However, not all pre-zygotic defects are present in mosaic: in many cases, the mutation is thought to arise in a single sperm or egg cell. The difference between the de novo vera mutation and the mutation derived from parental gonadal mosaicism is therefore evident. However, since it is not currently possible to perform a test to verify parental gonadal mosaicism, the two conditions are considered equally from a practical point of view. Therefore, an empirical reproductive risk of about 5% is given attributed in genetic counseling.


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