Medical Genetics - V. M. Zaporozhan 2005

Monogenic Disorders
Prenatal Diagnosis of Monogenic Disorders

The following Methods are used for prenatal Diagnosis.

1. Non-invasive method — ultrasound imaging to detect developmental malformations.

2. Invasive Methods (chorionic villus sampling, placentocentesis, amniocentesis, cordocentesis) are used to diagnose Monogenic Disorders that do not present phenotypically during Pregnancy (enzymopathies, neuromuscular disorders).

Indications for invasive Prenatal Diagnosis of Monogenic Diseases include a high risk of having an affected child in the following cases:

1) a dominantly inherited disorder in one of the parents. This approach is applied when the condition cannot be diagnosed via ultrasound (myotonic dystrophy, Huntington's disease, etc.);

2) both parents are heterozygous carriers of the same recessive pathological Gene;

3) the mother is a carrier of an X-linked recessive gene.

Evidence of carrying an autosomal recessive or X-linked gene can be the previous birth of an affected child or the results of parental laboratory testing.

Tissue samples obtained through invasive Procedures can be analyzed using the following approaches:

— molecular Genetic Methods (Examples of disorders that can be diagnosed prenatally using molecular genetic techniques are given in Table 6.11);

— Biochemical Methods (determination of lysosomal enzyme activity to diagnose Mucopolysaccharidoses, sphingolipidoses, etc.). Enzyme activity can be assessed in Amniotic Fluid or Cell cultures.

Invasive prenatal diagnosis is advisable in cases of severe, debilitating, and early fatal monogenic disorders. The first trimester of pregnancy is the optimal time for prenatal testing, as an unfavorable result allows for termination via a standard medical abortion.