What are microdeletion/microduplication syndromes?

What are microdeletion/microduplication syndromes?

A Genetic Counselor's perspective on microduplications/microdeletion syndromes, and how embryo screening can mitigate these risks

Written by Maria Katz, MS, CGC
Reviewed by Xiaoli Du, PhD, FACMG, DABMGG, CGC,CGMBS

Dr. Du is an American Board of Medical Genetics and Genomics (ABMGG) certified geneticist. With a passion for precision medicine, she leverages cutting-edge molecular genetics and cytogenetics technology to improve outcomes for individuals affected by genetic conditions. Dr. Du has nine years of clinical genetic diagnosis experience in both the public and private sectors.

What are microdeletions/microduplication syndromes?

Microdeletions and duplications are genetic abnormalities that involve the loss or duplication of a small segment of DNA from a chromosome. Unlike bigger genetic abnormalities like Down syndrome, which involve having an extra copy of an entire chromosome, microdeletions and duplications affect only a tiny portion of genetic material. These segments can range in size from a few hundred base pairs to several million.

Having extra or missing pieces of chromosomes can lead to various symptoms and health problems. This is because the genetic material contained within chromosomes carries important instructions for the development and functioning of our bodies. When there are changes in the number or structure of chromosomes, it can disrupt the normal balance of genetic information.

For example, in microdeletions, a small piece of DNA is lost, which means certain genes or regulatory regions may be missing. This can change how genes work, which can affect different processes in our bodies. On the other hand, in microduplications, there are extra copies of genetic material, which can disrupt the normal amount of genes and how they interact with each other. These imbalances can then interfere with our normal development and cause various symptoms and health issues.

How do microdeletions/duplications occur?

Microdeletions and microduplications can either occur by chance during conception or be passed down from parents to their children. When a microdeletion or duplication happens by chance, it is called "de novo." This means that it wasn't inherited from the parents, but rather it occurred during the formation of the reproductive cells (like sperm or eggs) or in the early stages of development of the embryo. On the other hand, microdeletions and duplications can also be inherited. This means that one or both parents have the microdeletion or duplication in their genes, and they pass it on to their children.

Symptoms and Characteristics

Microdeletions/duplications can interfere with normal development, leading to a wide range of symptoms depending on the genes involved and the specific chromosomal region affected. Symptoms can vary widely and may include neurodevelopmental disorders and birth defects.

It is important to note that the impact of these chromosomal abnormalities can vary from person to person. Some individuals may experience severe symptoms and health complications, while others may have milder or no noticeable effects. Additionally, the symptoms and severity can also be influenced by other factors, such as the specific genes involved, environmental influences, and individual variations.

A few common microdeletion/duplication conditions are:

  • 22q11.2 Deletion Syndrome (DiGeorge syndrome/velocardiofacial syndrome): This microdeletion involves a loss of a small piece of chromosome 22 and can affect various parts of the body and has a wide range of signs and symptoms, even among family members. Common features include heart abnormalities, immune system problems, developmental delays, and facial differences. 22q11.2 is estimated to occur in 1 in every 2000 - 6000 births.
  • Prader-Willi Syndrome: This microdeletion involves a loss of a piece of chromosome 15 coming from the sperm and occurs in 1/15 000–1/30 000 births. This condition is characterized by weak muscle tone, delayed development, hyperphagia (excessive eating), intellectual impairments and behavioral issues. 
  • Cri-du-Chat Syndrome: This microdeletion involves a loss of a small piece of chromosome 5, and results in a distinct cat-like cry in affected infants, along with intellectual disability, facial abnormalities, and developmental delays.Cri-du-Chat is estimated to occur in 1 in every 15,000 to 50,000 live births.

Microdeletions represent a unique group of genetic disorders that can have a significant impact on an individual's health and development. While each microdeletion and microduplication syndrome is rare on its own, when considered together, they are actually quite common. A study has estimated that around 1 in 200 individuals have a microdeletion or microduplication in a specific genomic region associated with various symptoms including neurodevelopmental disorders. These findings highlight the significant impact of these genetic variations on a larger scale.With advancements in prenatal testing, the possibility of detecting microdeletions before birth provides an opportunity for informed decision-making and appropriate medical management.

Can I test my embryos for microdeletions and microduplications?

Yes, Orchid screens embryos for chromosomal abnormalities, including microdeletions and microduplications. 

Large chromosomal abnormalities, like Down Syndrome (trisomy 21) are a common cause of pregnancy loss, accounting for around 40-50% of cases, and the chance to have a chromosomally abnormal embryo  increases as the mother gets older. However, microdeletions and duplications, are not specifically linked to maternal age and occur with similar prevalence in embryos across age groups.

Orchid focuses specifically on regions associated with microdeletions and duplications, which are known to contribute to birth defects, neurodevelopmental disorders, and other health concerns. These smaller genetic changes can be missed by other embryo screens that are unable to detect such subtle alterations. By targeting these specific regions, we ensure a more comprehensive and accurate screening that identifies potential risks often overlooked by other methods.

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