A microdeletion is a genetic anomaly where a small, specific piece of a chromosome is missing. Human cells contain 46 chromosomes organized into 23 pairs, which hold our DNA. This missing piece, though tiny, can contain multiple genes, and its absence can affect an individual’s health and development.
Imagine the genetic code as a massive encyclopedia. A microdeletion is like a single sentence being erased from one of the volumes. The rest of the book is intact, but the absence of that one sentence can change the meaning of the entire chapter.
Causes and Inheritance of Microdeletions
The majority of microdeletions are de novo, meaning they are new mutations that occur spontaneously. These random events happen during the formation of sperm or egg cells or very early in fetal development. In these cases, the microdeletion is not inherited and is not the result of any action by the parents.
Spontaneous deletions result from errors when cells divide and replicate their DNA. Complex regions of chromosomes with repetitive DNA sequences are more susceptible to mistakes during this process. No known lifestyle, dietary, or environmental factors can prevent these de novo occurrences.
In a smaller number of cases, a microdeletion is passed down from a parent to a child. This happens if a parent has the microdeletion but experiences very mild or undetectable symptoms. Another way inheritance occurs is through a “balanced translocation,” where a parent has a harmless rearrangement of their chromosomal material. This balanced arrangement can become unbalanced when passed to a child, resulting in a deletion.
Detection and Diagnosis
Identifying a microdeletion requires advanced genetic testing because the missing segments are too small for standard techniques. A historical test called a karyotype can spot large-scale changes, like a missing chromosome. However, it lacks the resolution to detect a subtle microdeletion.
The primary tool for detection is Chromosomal Microarray Analysis (CMA). This high-resolution test scans a person’s chromosomes for tiny missing or extra pieces of DNA. CMA works by comparing a patient’s DNA to a reference sample to identify discrepancies in genetic material. It is the standard for diagnosing conditions caused by microdeletions.
Another diagnostic tool is Fluorescence In Situ Hybridization (FISH), which is a targeted test unlike the genome-wide CMA. It uses fluorescent probes designed to attach to a specific, suspected region of a chromosome. If that segment is missing, the probe has nowhere to bind, confirming the microdeletion. This method is used when a doctor suspects a particular syndrome based on clinical features.
These diagnostic tests can be performed after birth on a blood sample. They can also be done prenatally through procedures like amniocentesis or chorionic villus sampling.
Associated Syndromes and Characteristics
Different microdeletions lead to distinct syndromes, each with its own set of characteristics. The severity and range of symptoms can also vary widely, even among individuals with the same deletion. The consequences are determined by the specific genes located within the lost chromosomal segment.
One of the most common microdeletion disorders is 22q11.2 deletion syndrome, also known as DiGeorge syndrome, which arises from a missing piece of chromosome 22. Individuals can have health issues including congenital heart defects, immune system problems, and palate differences. They may also experience developmental delays, learning difficulties, and have certain characteristic facial features.
Williams syndrome is caused by a deletion on chromosome 7 in the 7q11.23 region. This deletion includes the gene for elastin, a protein providing strength and elasticity to tissues. As a result, individuals often have cardiovascular problems, like a narrowing of the aorta called supravalvular aortic stenosis. People with Williams syndrome may have distinctive facial features and are often described as having a very sociable personality.
Cri-du-chat syndrome results from a deletion on the short (p) arm of chromosome 5. The name is French for “cat’s cry” and comes from the characteristic high-pitched cry of affected infants. Other features include low birth weight, poor muscle tone (hypotonia), a small head size (microcephaly), and developmental disabilities. The size of the deletion can influence the severity of symptoms.
Management and Support Strategies
The underlying genetic deletion cannot be reversed, but the associated health and developmental challenges can be managed. The approach to care is individualized, focusing on addressing specific symptoms. This involves a multidisciplinary team of specialists, such as a cardiologist for heart issues, an immunologist for immune deficiencies, and an endocrinologist for calcium problems.
Early intervention is important for managing microdeletion syndromes in children. Therapies like physical, occupational, and speech therapy help children with developmental delays achieve milestones and improve functional abilities. For instance, speech therapy can address challenges from cognitive delays or physical differences like a cleft palate.
Educational support is another component of management, and children may benefit from specialized programs for their learning styles. Genetic counseling is also a resource for families. Counselors provide information about the syndrome, discuss recurrence risks in future pregnancies, and offer emotional support to navigate the diagnosis.