Microdeletions

NIPT screening can assess risk for the most common microdeletion syndromes, including 22q11.2 deletion syndrome (DiGeorge syndrome). This blood test can be performed from 10 weeks of pregnancy and analyses cell-free fetal DNA circulating in maternal blood. The test provides a risk assessment for several microdeletion conditions with established accuracy rates.

Multiple NIPT options are available, including SMART Test NIPT and KNOVA NIPT by Fulgent, each with different microdeletion screening panels. The most appropriate test can be selected based on individual circumstances and screening preferences.

Genetic counselling is available both before and after microdeletion screening. Both 30-minute and 60-minute genetic counselling sessions can be arranged to discuss family history, explain screening options, and help with understanding test results. Pre-test counselling ensures full information is available about what screening involves and what results might mean.

Following screening, detailed explanation of results may be provided, including discussion of any increased risks identified and guidance through next steps. If diagnostic testing is recommended, the procedures involved can be explained and support provided through the decision-making process.

Advanced ultrasound examinations include comprehensive anomaly scans that can identify structural abnormalities associated with microdeletion syndromes. These detailed scans examine fetal anatomy for features that might suggest specific genetic conditions. Early detection of structural abnormalities can prompt further genetic testing and assist with pregnancy management.

Specialised fetal echocardiography is available for detailed cardiac assessment, as heart defects are commonly associated with several microdeletion syndromes. Advanced equipment can provide detailed fetal assessment when required.

For couples planning pregnancy or in early pregnancy, comprehensive carrier screening is available to assess risk for various genetic conditions. Whilst most microdeletions occur randomly, some may be inherited from asymptomatic parents. Understanding carrier status can inform reproductive choices and screening decisions.

Carrier screening programmes can identify couples at increased risk for various genetic conditions, allowing for informed family planning and appropriate prenatal monitoring. Results can be reviewed with genetic counsellors to ensure the implications for current and future pregnancies are understood.

When screening results suggest increased risk for microdeletions, support is available for diagnostic testing procedures. Amniocentesis can provide definitive diagnosis through chromosomal microarray analysis, which can detect microdeletions with high precision. The procedure is performed by experienced specialists with careful ultrasound guidance.

Thorough pre-procedure counselling is provided, explaining the diagnostic process, accuracy rates, and associated risks. Post-procedure support includes result interpretation and ongoing counselling to help with understanding the implications for pregnancy and future family planning.

Microdeletions are tiny missing pieces of chromosomes that are smaller than 5 million base pairs and involve several genes. They are too small to be detected by conventional chromosome analysis or high-resolution karyotyping, requiring specialised genetic testing methods such as fluorescence in situ hybridisation (FISH) or chromosomal microarray analysis. Microdeletions can affect various genes and may lead to developmental abnormalities, learning difficulties, or medical conditions.

Unlike larger chromosomal abnormalities such as Down syndrome, microdeletions involve the loss of relatively small chromosomal segments but can still have significant effects on development. The impact depends on which genes are deleted and their role in normal development and body function.

Most microdeletions occur spontaneously during the formation of reproductive cells (eggs or sperm) or early embryonic development. They result from errors in chromosomal recombination, where genetic material is not properly exchanged between chromosome pairs. These events are generally random and are not caused by any parental actions during pregnancy.

Whilst most microdeletions are new (de novo) occurrences, some can be inherited from a parent who carries the microdeletion but may have mild or no symptoms. Advanced parental age may slightly increase the risk of some chromosomal abnormalities, but microdeletions can occur in pregnancies of parents of any age.

Microdeletions are diagnosed through specialised genetic testing that can detect small chromosomal deletions. Screening during pregnancy is available through Non-Invasive Prenatal Testing (NIPT), which analyses cell-free fetal DNA in maternal blood from 10 weeks of pregnancy. NIPT provides a risk assessment for the most common microdeletion syndromes with established accuracy rates.

If screening suggests increased risk, diagnostic testing through chorionic villus sampling (CVS) or amniocentesis can provide definitive diagnosis using chromosomal microarray analysis. This technique can detect microdeletions with high precision and confirm whether the fetus is affected.

Symptoms of microdeletion syndromes vary significantly depending on which genes are deleted and their role in development. 22q11.2 deletion syndrome, the most common microdeletion, may cause heart defects, immune system problems, cleft palate, learning difficulties, and distinctive facial features. Other microdeletion syndromes may affect different organ systems and developmental processes.

Some individuals with microdeletions may have mild symptoms or appear completely normal, whilst others may have significant developmental delays, medical problems, or learning difficulties. The wide range of possible effects makes genetic counselling important for understanding the specific implications of each microdeletion syndrome.

Most microdeletions occur spontaneously and are not inherited from parents. However, some microdeletions can be passed from parent to child, particularly if a parent carries the microdeletion but has mild or no symptoms. When inherited, the pattern is typically autosomal dominant, meaning only one copy of the deleted chromosomal segment is needed to cause the condition.

If a parent carries a microdeletion, there is typically a 50% chance of passing it to each child. However, the expression of symptoms can vary significantly even within families, with some family members more severely affected than others. Genetic counselling can help assess recurrence risks for future pregnancies.

22q11.2 deletion syndrome (also known as DiGeorge syndrome or velocardiofacial syndrome) is the most common microdeletion syndrome, affecting approximately 1 in 1,524 pregnancies according to recent studies. This condition can cause heart defects, immune system problems, cleft palate, kidney abnormalities, learning difficulties, and psychiatric conditions.

Other relatively common microdeletions include 1p36 deletion syndrome, Williams-Beuren syndrome (7q11.23 deletion), and Prader-Willi/Angelman syndromes (15q11-q13 deletion). However, researchers have identified more than 200 different microdeletion syndromes, many of which are extremely rare and affect only a few individuals worldwide.

NIPT has established accuracy rates for detecting the most common microdeletion syndromes, particularly 22q11.2 deletion syndrome. Detection rates vary depending on the specific microdeletion and the testing methodology used. For 22q11.2 deletion syndrome, the largest prospective study (the SMART study) reported a detection rate of around 75-83% but a positive predictive value of only about 24-53%, meaning that because these conditions are rare, many high-chance results turn out to be false positives. NIPT is therefore a screening test that estimates risk rather than providing a definitive diagnosis.

Every high-chance NIPT result must be confirmed by diagnostic testing such as amniocentesis or chorionic villus sampling with chromosomal microarray analysis before any decisions are made. Because microdeletions are rare, a high-chance screening result is more likely to be a false positive than it is for the common trisomies, so it is important to understand that NIPT provides a risk assessment rather than a definitive answer about fetal genetic status.

Microdeletion screening may be considered for all pregnancies as these conditions can occur randomly regardless of maternal age or family history. Many healthcare providers now offer NIPT including microdeletion screening as part of routine prenatal care. Screening may be particularly relevant if ultrasound findings suggest possible structural abnormalities associated with microdeletion syndromes.

Specific indications for screening include fetal heart defects, growth restriction, or other structural abnormalities detected during routine anomaly scanning. Family history of microdeletion syndromes or previous affected pregnancies also warrant consideration of screening or diagnostic testing.

If microdeletions are detected during pregnancy, comprehensive genetic counselling is available to help understand the implications for the current pregnancy and future family planning. The impact varies significantly depending on the specific microdeletion and can range from minimal effects to significant developmental and medical problems.

Management may include detailed ultrasound monitoring to assess for associated structural abnormalities, specialist consultations with relevant medical teams, and planning for appropriate delivery and neonatal care. Early identification allows for preparation and ensures appropriate medical support can be arranged for after birth.

Microdeletions cannot be corrected or cured as they involve permanent genetic changes. However, many of the associated medical problems can be treated or managed effectively. For example, heart defects can often be surgically repaired, immune system problems can be managed with appropriate medical care, and educational support can help with learning difficulties.

Early intervention and multidisciplinary care can significantly improve outcomes for individuals with microdeletion syndromes. This may include cardiac surgery, speech therapy, educational support, and ongoing medical monitoring. The specific treatments required depend on which organs and systems are affected by the particular microdeletion.

Pregnancy outcomes with microdeletions vary significantly depending on the specific syndrome and severity of associated abnormalities. Some pregnancies with microdeletions may proceed normally with minimal complications, whilst others may be associated with structural abnormalities, growth restriction, or pregnancy loss.

Careful monitoring throughout pregnancy may be recommended, including detailed ultrasound assessments and appropriate specialist consultations. Planning for delivery should consider any anticipated medical needs of the baby, ensuring appropriate specialist care is available immediately after birth.

Comprehensive support includes genetic counselling to help families understand the condition and its implications, specialist medical care for associated health problems, and educational support for learning difficulties. Many microdeletion syndromes have dedicated patient support groups that provide information, resources, and connection with other affected families.

Multidisciplinary care teams typically include geneticists, cardiologists, immunologists, speech therapists, and educational specialists as needed. Early intervention services can help optimise development and outcomes for children with microdeletion syndromes. Genetic counselling can help connect families with appropriate support resources and specialist services.

If a microdeletion occurs spontaneously (de novo), the recurrence risk for future pregnancies is generally low, similar to the background population risk. However, if either parent is found to carry the microdeletion, there may be up to a 50% chance of recurrence in each subsequent pregnancy.

Parental testing following diagnosis of a fetal microdeletion is important to determine recurrence risks and inform family planning decisions. Preconception genetic counselling and early prenatal screening or diagnosis can be offered for subsequent pregnancies depending on the specific circumstances and family wishes.

Ultrasound signs associated with microdeletions are suggestive rather than diagnostic and many affected pregnancies may show no obvious structural abnormalities during routine scanning. However, certain features such as heart defects, growth restriction, or specific anatomical abnormalities may increase suspicion for microdeletion syndromes.

The detection of structural abnormalities during detailed anomaly scanning may prompt consideration of genetic testing, but normal ultrasound findings do not rule out microdeletion syndromes. This is why screening tests such as NIPT are valuable for detecting these conditions even when ultrasound appears normal.

Screening tests such as NIPT estimate the probability that a pregnancy is affected by microdeletions but do not provide definitive answers. These tests analyse cell-free DNA in maternal blood and have established detection rates with very low risk to the pregnancy. Screening results are reported as high or low risk rather than positive or negative.

Diagnostic tests such as amniocentesis with chromosomal microarray analysis can definitively confirm or rule out microdeletions. These tests analyse fetal cells directly and provide definitive genetic information, but involve a small risk of pregnancy complications. Diagnostic testing is usually recommended when screening suggests increased risk.

Microdeletions generally occur randomly during reproductive cell formation or early embryonic development and are not typically influenced by lifestyle factors, environmental exposures, or parental behaviour. Unlike some birth defects that may be prevented through dietary supplementation or lifestyle modifications, microdeletions are usually spontaneous genetic events.

Maintaining good general health during pregnancy through appropriate nutrition, prenatal vitamins, and regular medical care is always important, but these measures do not specifically prevent microdeletions. The focus should be on appropriate screening and early detection rather than prevention strategies.

This page was created using information from the following trusted medical sources:

• Microduplication and Microdeletion Syndromes Diagnosed Prenatally Using Single Nucleotide Polymorphism Array – PMC
• Y chromosome microdeletion – South East Genomics : South East Genomics
• Deletions and microdeletions — Knowledge Hub
• Y chromosome microdeletion – North Thames GMS : North Thames GMS
• Clinical Background and Genetics:
• Stgeorges
• 2q23.1 microdeletion syndrome | About the Disease | GARD