Introduction
Deletions covering at least five megabases (Mb) are typically microscopically discernible in chromosome-banded karyotypes. Chromosome deletions that are too small to be seen by traditional cytogenetic techniques utilizing light microscopy are known as microdeletions or submicroscopic deletions. Specialized testing is required to find these deletions. Microdeletions often span 1 to 3 Mb and affect numerous adjacent genes. Although a microdeletion's precise shape and position that results in a syndrome can differ, a particular "critical area" is invariably implicated. The majority of these microdeletions' phenotypic impacts are brought about by the haploinsufficiency (when one copy of a gene is inactivated or deleted and the other functional copy of the gene is insufficient to create the required gene product to maintain normal function) of a few crucial genes, or occasionally just one gene.
What Happens During Microdeletion?
Genomic disorders are illnesses brought on by chromosomal or genetic material lost or gained. The two main groups of the most prevalent and well-understood genomic illnesses are those caused by copy number losses (deletion syndromes) and those caused by copy number gains (duplication syndromes).
DNA (deoxyribonucleic acid) gains or losses are caused by copy number variations (CNVs), which are submicroscopic genomic alterations in the number of copies of one or more DNA regions. The same CNVs can be linked to several illnesses, and some CNVs are linked to disease susceptibility or resistance. Still, other CNVs are unrelated to known diseases and are a typical component of genomic diversity.
When CNVs impact numerous nearby genes, neighboring gene syndromes may result. Genomic diseases are characterized by a change in the copy number of a dose-sensitive gene or genes due to a deletion or duplication. As a result, the gene changes how much protein is produced. The discovery of recessive illnesses, the disruption of imprinted genes, and the disruption of regulatory elements outside of genes are different disease processes.
When a section of a chromosome is missing, an anomaly known as a microdeletion results, and a total of 46 chromosomes, 23 from each parent, are found in almost all of our cells. The body breaks these DNA strands into smaller pieces during cell division. But, occasionally, a very small portion of a chromosome gets cut during this process, creating microdeletion. Depending on its location and size, microdeletion can negatively or positively impact a baby's health and development. While some microdeletions have no negative effects, others might result in intellectual disability, issues with motor abilities, or miscarriage.
Are Microdeletions Common?
Microdeletions appear to occur randomly, which means they typically don't run in families and affect all babies equally regardless of other risk factors, in contrast to other chromosomal abnormalities, which are more likely to occur in mothers with certain risk factors, such as those who are 35 years of age or older or who have a family history of a genetic disorder. In fact, according to some estimations, almost all people have some chromosomal deletion. For instance, the rare deletion syndrome affects one in 4,000 individuals. Yet, this illness might need to be recognized appropriately, which might happen more frequently. Some well-known microdeletion syndromes include:
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22q11.2 Deletion Syndrome (DiGeorge Syndrome or Velocardiofacial Syndrome): This is one of the most common microdeletion syndromes, occurring in approximately one in 2,000 to 4,000 live births. It can cause many symptoms, including heart defects, immune system problems, developmental delays, and characteristic facial features.
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Cri-Du-Chat Syndrome: This syndrome is caused by a deletion on the short arm of chromosome 5. It is estimated to occur in approximately one in 20,000 to 50,000 live births. Affected individuals often have a high-pitched cry (resembling a cat's cry), intellectual disability, and distinctive facial features.
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Prader-Willi Syndrome: This is a complex genetic disorder caused by the absence of a specific segment of chromosome 15. It occurs in approximately one in 10,000 to 30,000 live births. Prader-Willi syndrome is characterized by feeding difficulties in infancy, excessive hunger leading to obesity, intellectual disability, and other physical and behavioral features.
It is important to note that microdeletions can vary in their frequency and clinical impact. Some microdeletions may be extremely rare, while others are relatively more common. Genetic testing and advances in diagnostic techniques have improved the ability to identify and diagnose microdeletions, even in individuals without obvious symptoms. However, the overall prevalence of microdeletions as a group needs to be well-established due to the wide range of potential deletions and their varying frequencies.
Will a Non-Invasive Prenatal Testing (NIPT) Include Microdeletions?
The non-invasive prenatal test is one examination that expectant mothers frequently obtain after nine weeks (NIPT). This blood test reveals details on the condition of the still-developing child. The most prevalent chromosomal diseases NIPT detects are trisomy 21 (Downs syndrome), trisomy 18 (Edwards syndrome), and trisomy 13 (Patau syndrome). Five chromosomal pairs are screened for using an enhanced NIPT, which may also find particular microdeletions. Yet the NIPT is only one of several exams the doctor can perform to let know how the unborn child develops and what results are possible.
Even though the NIPT has a 99 percent overall success rate in detecting chromosomal abnormalities, it is still only a screening test. Consider going beyond NIPT and having the practitioner order further tests like amniocentesis or chorionic villus sampling (CVS) with microarray testing if the family has a history of intellectual developmental impairment.
Amniocentesis or CVS are the only samples that can be used for microarray testing. These tests are more sophisticated than NIPT and can examine chromosomes to see if they have extra information or are missing some DNA.
What Does It Mean if the Person Gets a Positive Result?
If an expanded NIPT uncovers a microdeletion, people should remember that this is not a diagnostic test and can only estimate the likelihood that the baby has a specific problem. However, if it is high enough, the doctor may advise speaking with a genetic fetal medicine specialist or doing additional testing, such as a microarray test, amniocentesis, or CVS—invasive procedures with a very low risk of harm to the unborn child but provide a certain diagnosis.
Knowing ahead of time enables taking action to enhance the baby's health and quality of life if additional testing reveals that the baby has a microdeletion. Although there is no cure, there is numerous therapy available. People can work with medical professionals to correct cardiac, neurological, palatal, bone, immunological, hearing, or vision issues as soon as the kid is born. At this time, people can get a complete evaluation. For instance, prenatal testing ensures doctors know they must check these levels from birth and supplement as necessary. Babies with 22q deletion syndrome have a tougher problem retaining calcium. Prenatal conditions are disclosed to parents so they can make adequate preparations. Before having tests like NIPT, CVS, and amniocentesis, some parents could experience anxiety and concern.
Conclusion
This blood test reveals details on the condition of the still-developing child. The most prevalent chromosomal diseases NIPT detects are trisomy 21 (Downs syndrome), trisomy 18 (Edwards syndrome), and trisomy 13 (Patau syndrome). Little subchromosomal deletions and duplications that could not be found by traditional karyotyping can now be found with NIPT technology because of the advances in whole-genome sequencing technology.
