Birth defects-what are they? Birth defects in the fetus are any anatomical, chromosomal, molecular abnormalities that arise during pregnancy. These are genetic defects and those caused by mom’s infections, her use of certain drugs, alcohol, etc. What are the most common fetal malformations?

Congenital malformations of the fetus occur in 2-4 percent. children. They can be detected and treated already during pregnancy thanks to prenatal tests (ultrasound, genetic tests). Fetal birth defects are treated surgically (some even by termination of pregnancy), and also corrected by rehabilitation.

Malformations in children lead to abnormalities in the construction of various parts of the body of the fetus, including internal organs. It often leads to miscarriage, and sometimes to death in infancy. Here are the most common birth defects of the fetus.

Birth defects-what are they?

Methods for studying the genetic background of congenital malformations
Advances in molecular biology have made it possible to identify numerous genes that affect the process of morphogenesis. The chapter provides a brief overview of the methods used in genetic diagnosis and in the study of the molecular basis of congenital malformations, including: cytogenetic studies, microduplication and genomic microdeletion studies using micromatersors, conjugation and sequencing studies in the detection of rare mutations, whole genome association studies (GWAS) in the detection of common risk alleles and studies in animal models.

Cytogenetic studies

In the study of the causes of congenital malformations syndromes, classical cytogenetics tests are still used, which allow the identification of aberrations in the number and structure of chromosomes and are still the basic test used in the diagnosis of genetic multiple defects, although they are increasingly being replaced by the study using the method of comparative genomic hybridization to micrometers (aCGH).

The limitation of classical cytogenetic studies is their low resolution-changes of 5-10 MB can be detected. Detection of submicroscopic structural abnormalities of chromosomes, such as interstitial deletion 22q11.2, lies at the limit of the resolution of the light microscope. This type of chromosomal micro-rearrangement has often been detected using the high resolution technique (HRT), which has enabled the identification of approx. 1,000 striae in a haploid set of chromosomes.

An important advance in cytogenetic research was the introduction of fluorescence in situ hybridization (fish), which allowed the identification of much smaller chromosomal aberrations (Driscoll et al., 1993; Wozniak et al., 2010).

Currently, the multiplex ligation dependent probe amplification (MLPA) method is used in genetic studies of specific microdeletion and microduplication syndromes. MLPA compared to fish allows multiple chromosome regions to be analyzed in a single study depending on the set of probes (Fernandez et al., 2005). MLPA kits have been developed to detect microdeletions and microduplications located in subtelomeric regions and to identify 40 known syndromes caused by this type of micro-rearrangement. For the application of MLPA, it is important to know the phenotype of the microabersion syndrome. Establishing a clinical diagnosis of a particular syndrome is difficult in young children, especially in neonates, as typical signs of microdeletion syndromes may emerge later in life.

Microdeletion and microduplication analysis with aCGH and oligonucleotide matrices

The possibility of studying the genetic condition of birth defects is also provided by studies of the variability of the number of copies of DNA-CNVs (copy number variants). CNVs are segments of microdeletion or microduplication in the genome that may represent rare or common variants of a norm or pathological variants. Variation in the number of DNA copies (CNV) is an important source of interpersonal genetic variation, which may explain the different expression of genetically determined diseases, the different phenotype of monogenic and multicellular diseases, and thus also congenital malformations (Beckmann et al., 2007).

Microdeletions and microduplications, apart from FISH and MLPA techniques mentioned above, are detectable using two methods:

  • array comparative GE-nomic hybridization (array CGH),
  • oligonucleotide micromatering methods also used in GWAS studies.


Acgh micromatering has become a powerful, state-of-the-art tool for high-resolution genome analysis and detection of CNV micro-rearrangements. The clinical consequences of a large group of these aberrations are unknown. An important problem is therefore the interpretation of new variants in relation to a particular phenotype. In order to identify pathological variants, it is also important to know which variants have no pathological significance and are common in the healthy population. Databases with non-pathological CNVs imbalances have been created and are continuously updated.