A microdeletion refers to a tiny, missing segment of genetic material on a chromosome. These chromosomes house our DNA, which contains thousands of genes. A microdeletion is like a few missing words from a very large genetic book.
This small missing piece is too minute to be observed using a standard microscope. Despite their small size, microdeletions can affect several genes within the deleted segment. These affected genes can be important for growth and development, potentially leading to various health or developmental differences.
Causes of Microdeletions
Microdeletions primarily arise from spontaneous events, meaning they occur randomly. These new genetic changes, known as “de novo” mutations, typically happen during the formation of sperm or egg cells or very early in fetal development due to an error in DNA replication.
Such occurrences are generally not linked to specific parental actions or environmental factors. In some instances, a microdeletion can be inherited from a parent. A parent might carry the deletion with no noticeable health effects, or they might have a milder form of the associated condition.
When a microdeletion is inherited, the parent has a 50% chance of passing it on with each pregnancy. If a microdeletion is determined to be de novo, the chance of it recurring in future pregnancies is estimated to be less than 1%.
Detection and Diagnosis
Identifying microdeletions involves specialized genetic tests. For expectant parents, prenatal testing begins with screening options. Non-invasive prenatal testing (NIPT) analyzes cell-free fetal DNA in the mother’s blood, typically performed after 10 weeks of pregnancy. NIPT can identify an increased likelihood for certain microdeletion syndromes, but it is a screening tool, not a definitive diagnosis.
If NIPT results suggest a higher risk, or if there are other indications, diagnostic tests are recommended for confirmation. These invasive prenatal procedures include chorionic villus sampling (CVS), usually performed between 11 and 14 weeks of pregnancy, and amniocentesis, typically done after week 15. Both CVS and amniocentesis collect fetal cells for direct genetic analysis.
For both prenatal and postnatal diagnosis, chromosomal microarray analysis (CMA) is a standard technology for detecting microdeletions and microduplications. CMA works by detecting imbalances in DNA copy number, revealing submicroscopic losses or gains of genetic material that are too small for conventional karyotyping.
Common Microdeletion Syndromes
Microdeletions can lead to various syndromes, each with unique features. One example is 22q11.2 deletion syndrome, also known as DiGeorge syndrome. This condition is caused by a deletion on chromosome 22 and can affect multiple body systems. Individuals might experience congenital heart defects, palatal abnormalities, immune deficiencies, and low calcium levels. Developmental delays, learning difficulties, and an increased risk for psychiatric conditions are also common.
Williams syndrome results from a deletion on chromosome 7, specifically at 7q11.23. This syndrome is characterized by distinctive facial features, including a broad forehead, full cheeks, and an upturned nose. Individuals often have a sociable personality, mild to moderate intellectual disability, and challenges with visual-spatial tasks. Cardiovascular problems, particularly supravalvular aortic stenosis, are frequently observed.
Prader-Willi syndrome and Angelman syndrome are two distinct conditions caused by deletions on chromosome 15, specifically in the 15q11-q13 region. Prader-Willi syndrome typically involves a deletion on the paternally inherited chromosome. Infants with Prader-Willi often present with weak muscle tone and feeding difficulties, which later transitions to excessive hunger (hyperphagia) leading to obesity if not managed. Developmental delays, cognitive impairment, and behavioral issues are also common.
Angelman syndrome, conversely, is associated with a deletion on the maternally inherited chromosome 15. Children with Angelman syndrome often exhibit severe developmental delays, significant speech impairment, and problems with balance and coordination (ataxia). A unique behavioral characteristic is a consistently happy demeanor, with frequent laughter, smiling, and hand-flapping movements. Seizures and sleep disturbances are also common features.
Management and Support Systems
Upon diagnosis of a microdeletion syndrome, the focus shifts to managing the specific symptoms and supporting the individual’s development. Since microdeletions are alterations in the genetic code, there is no cure for the deletion itself. Instead, care involves a comprehensive approach to address the diverse challenges that may arise.
A multidisciplinary care team is assembled to provide specialized support. This team might include pediatricians, cardiologists, immunologists, and various therapists (speech, physical, occupational) to assist with developmental progress. Early intervention services are beneficial, as they can help maximize developmental potential by providing individualized support and therapies.
Genetic counseling helps families understand the microdeletion, its potential implications, and recurrence risks. Counselors provide information, support decision-making regarding genetic testing, and help families adapt to the diagnosis. Connecting with disease-specific support groups can also be valuable, offering a network for families to share experiences, gain insights, and find emotional support.