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Microdeletion syndromes – a group of disorders that miss the screening net


Dr Priya Kadam, Program Director-NIPT, MedGenome, highlights the second most common chromosomal abnormality after Down syndrome- microdeletion syndromes and shares the need to create awareness about the same

Dr Priya Kadam

Earlier this year, when 39-year-old Juhi* was pregnant again she was engulfed with a nagging worry. Her previous pregnancy has been affected with Down syndrome. She approached a well-known genetic consultant for advice. The consultant suggested a new test to screen for Down syndrome and also another clinically relevant group of abnormalities known as microdeletion syndromes. This test was non-invasive, safe and accurate. She decided to undergo the test and received the results within a week. Unfortunately, the baby was affected with a condition known as 22q11.2 microdeletion syndrome. Though the family was shocked with the result, she was thankful for the information early in pregnancy.

Most people are aware of Down syndrome as the most common chromosomal abnormality. These children are intellectually impaired and present with characteristic features that include congenital heart diseases. The reason why most people are aware of this disorder is because; firstly it is common, with an incidence one in every 800 pregnancies. Secondly, a screening protocol is in place. Thirdly, all professional societies recommend screening for all pregnant women for chromosomal abnormalities, particularly Down syndrome.

However, there is another group of disorders, equally important and common, called microdeletion syndromes. This group of disorders is a significant cause of developmental delay, intellectual abnormalities, structural defects and/ or organ malformations like congenital heart disease. The frequency of these syndromes approaches one in every 1000 births. Interestingly, unlike Down syndrome where the risk rises with increasing maternal age, the risk of a pregnant woman carrying a baby with microdeletion syndrome remains the same throughout reproductive period. As a corollary, a younger pregnant woman is more likely to be carrying a baby with a microdeletion syndrome than a Downs baby.

It is obvious that the birth of an affected child causes immense emotional, social and financial challenge to the family. But can these syndromes be detected during pregnancy? Unlike the screening tests available for Down syndrome, there is no formal screening protocol for microdeletions. Rarely, a detailed pregnancy ultrasound may raise suspicion of these disorders if a structural defect such as a heart defect is found.

What is the cause of these disorders? A loss of a specific small part of a chromosome leads to a microdeletion syndrome. The deletions occur most often as a random event during the formation of reproductive cells (eggs or sperm) or in early fetal development. This loss of a part of the chromosome is permanent.

Are these inherited? Do parents pass on this disorder to their children? A very small number do. For example, about 5-10% of the most common microdeletion syndrome, 22q11.2/DiGeorge microdeletion syndrome is inherited. Either parent may be affected. Most microdeletion syndromes are not inherited. The affected typically have no history of the disorder in their family. Many disorders are so severe that individuals affected with these disorders often do not reproduce.

With the development of new technologies, the genetic cause more and more of these syndromes have been identified. 22q11.2 microdeletion syndrome is the second most common chromosomal abnormality after Down syndrome. The diagnosis of the condition is often delayed. Infact, parents of these children often undergo, a ‘diagnostic odyssey’ trying to identify the cause of their childs’ problems. These children usually suffer from fits soon after birth, may catch infections repeatedly in early infancy because of problems in the immune system and may have structural heart problems. As they grow into their teens they may develop psychiatric illnesses such as schizophrenia. The other less common microdeletions include, Angelman syndrome, Prader-Willi syndrome, Cri-du-chat syndrome among others. Most disorders are associated with moderate to severe intellectual impairment. The symptoms and manifestation of microdeletion syndromes vary widely.

What is the management of these conditions? It is clear that at present there is no cure. Only supportive management is possible. However, clinically relevant microdeletions can be screened during pregnancy with a new test. The test is called non-invasive prenatal screening. A small amount of blood from the mothers arm is investigated for the cell-free DNA from the growing baby. This can tell scientist/ clinicians of the possibility of the baby being affected by these conditions. Having this information can empower the parents to make informed choices, enable them to be fully aware of these conditions and seek medical help. An effort should be made to educate prospective parents so that these conditions do not miss the early screening net.

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