A microdeletion is a very small piece of genetic material missing from a chromosome. This absence of genetic information can affect how the body develops and functions. The missing segment typically includes only a few genes or parts of genes.
The Genetic Basis of Microdeletions
Our bodies are built according to instructions within our chromosomes, structures found inside almost every cell. Humans typically have 23 pairs of chromosomes, with one set inherited from each parent. These chromosomes are long strands of DNA packed with thousands of genes, which are the individual units of heredity.
Microdeletions often arise as random errors during the formation of reproductive cells, such as sperm or eggs. This occurs when chromosomes misalign or rearrange incorrectly during cell division, leading to a small segment being left out. In some rare instances, a parent might carry a balanced chromosomal rearrangement that does not cause symptoms in them but can lead to a microdeletion or microduplication in their offspring. These deletions are too small to be identified through a standard karyotype.
Examples of Microdeletion Syndromes
The specific effects of a microdeletion depend on which genes are missing and from which chromosome they are deleted. Different chromosomal locations lead to distinct sets of characteristics, often grouped into specific syndromes.
One well-known example is 22q11.2 deletion syndrome, also called DiGeorge syndrome, caused by a missing segment on the long arm of chromosome 22. Individuals with this syndrome may experience heart defects, immune system problems, and distinctive facial features. They can also have difficulties with speech and learning, along with a higher risk of psychiatric conditions later in life.
Another example is Cri-du-chat syndrome, or 5p deletion syndrome, which results from a missing part on the short arm of chromosome 5. A characteristic high-pitched cry resembling a cat’s meow is often observed in infants with this condition. Children with Cri-du-chat syndrome typically experience significant developmental delays, intellectual disabilities, and microcephaly.
Williams syndrome is associated with a microdeletion on chromosome 7, specifically involving the _ELN_ gene, among others. This condition often presents with a unique personality characterized by an overly friendly demeanor, alongside distinctive facial features, cardiovascular problems, and mild to moderate intellectual disability.
Diagnosis and Genetic Testing
Detecting microdeletions requires specialized genetic testing methods that can identify very small changes in chromosomal structure. These deletions are too subtle to be seen using traditional microscopy techniques.
One such technique is Fluorescence In Situ Hybridization (FISH), which uses fluorescent probes designed to bind to specific DNA sequences on a chromosome. If the targeted segment is missing, the probe will not bind, indicating a deletion.
Chromosomal Microarray Analysis (CMA) is another diagnostic tool for detecting microdeletions and microduplications across the entire genome. CMA compares a patient’s DNA to a reference DNA sample, allowing scientists to identify areas where the patient has missing or extra genetic material. This method can detect deletions much smaller than those found by FISH and does not require a specific region to be suspected beforehand. These tests are frequently performed when a child presents with unexplained developmental delays, intellectual disabilities, or multiple congenital anomalies, and they can also be part of prenatal diagnostic workups.
Management and Support Strategies
There is currently no way to replace the missing genetic material that causes a microdeletion. Therefore, management focuses on addressing the specific symptoms and developmental challenges an individual experiences. This often involves a comprehensive and coordinated approach from a multidisciplinary team of healthcare professionals.
A care team may include specialists such as cardiologists for heart conditions, immunologists for immune system issues, and endocrinologists for hormonal imbalances. Developmental pediatricians play a central role in overseeing overall care and coordinating various therapies. Early intervention therapies, including physical therapy to improve motor skills, occupational therapy to enhance daily living skills, and speech therapy to develop communication abilities, are frequently recommended and can significantly improve outcomes. Educational support and behavioral therapies are also often implemented to help individuals reach their full potential.