A deletion syndrome is a type of genetic condition that occurs when a small piece of a chromosome is missing. These missing segments can contain a few or many genes, which are the instructions that guide the body’s growth, development, and function. The absence of these genes can lead to a variety of effects on an individual’s health and physical characteristics. Because different chromosomes contain different sets of instructions, the specific traits of a deletion syndrome depend on which piece of which chromosome is absent. The range and severity of these traits can differ widely from one person to another, even among individuals with the same syndrome.
The Genetic Basis of Deletion Syndromes
Human cells contain 46 chromosomes arranged in 23 pairs, which can be thought of as a multi-volume instruction manual for the body. Each chromosome is a tightly coiled strand of DNA, and genes are specific sections of this DNA that provide instructions for building proteins and directing bodily functions. The size of a missing piece can vary; some are large enough to be seen with a standard microscope, while others, known as microdeletions, are much smaller and require more sensitive molecular techniques to detect.
The impact of a deletion depends on the size and location of the missing segment. The loss of even a small number of genes can disrupt normal development if those genes have functions in building organs or regulating bodily systems. In most cases, these deletions are not inherited from a parent. Instead, they occur as random, spontaneous events during the formation of reproductive cells or in the early stages of fetal development. This type of new genetic change is referred to as “de novo,” and most instances appear in families with no prior history of the disorder.
Common Deletion Syndromes and Associated Traits
One of the most frequently occurring deletion syndromes is 22q11.2 deletion syndrome, also known as DiGeorge syndrome, which results from a missing piece of chromosome 22. Heart defects present at birth are very common, as are problems with the palate, which can cause difficulties with feeding and lead to speech that sounds nasal. Many also have a weakened immune system due to an underdeveloped thymus gland, leading to frequent infections. Some experience low calcium levels, which can cause seizures, and distinctive facial features may include a small mouth, hooded eyelids, and small ears.
Another recognized condition is Cri-du-chat syndrome, caused by a deletion on the short arm of chromosome 5. Its name, French for “cry of the cat,” comes from the characteristic high-pitched cry that affected infants often produce due to abnormal development of the larynx. Traits associated with Cri-du-chat syndrome include low birth weight, poor muscle tone in infancy, and a small head size. Facial features often include widely spaced eyes, a small jaw, and a rounded face, and developmental delays are also common.
Wolf-Hirschhorn syndrome is caused by the deletion of a segment from the short arm of chromosome 4. A defining characteristic is the distinctive facial appearance, often described as a “Greek warrior helmet,” which includes a broad, flat nasal bridge and a high forehead. Growth is often delayed, beginning before birth, and feeding difficulties are common in infancy. Individuals with this syndrome have significant intellectual disability, and seizures are a frequent occurrence. Other potential issues include skeletal abnormalities and defects in the heart or urinary tract.
The Diagnostic Process
The identification of a deletion syndrome can happen before birth or after a child is born. Prenatal diagnosis often begins with screening tests that indicate a higher chance of a chromosomal condition. Noninvasive prenatal testing (NIPT) is a blood test that analyzes small fragments of the baby’s DNA in the mother’s bloodstream and can screen for certain microdeletions as early as nine weeks into pregnancy. If a screening test shows an elevated risk, more definitive diagnostic tests may be offered.
Chorionic villus sampling (CVS) and amniocentesis are two such diagnostic procedures. CVS involves taking a small sample of tissue from the placenta, while amniocentesis involves sampling the amniotic fluid surrounding the fetus. Both procedures carry a small risk but can provide a definitive diagnosis by directly analyzing the fetal chromosomes. These tests can identify larger deletions as well as smaller microdeletions.
After birth, a diagnosis might be suspected based on a baby’s physical characteristics or the presence of birth defects. A doctor may recommend genetic testing based on a physical examination. The primary test used to confirm a deletion syndrome is a chromosomal microarray analysis (CMA). This sensitive technology can detect very small missing or extra pieces of chromosomes that are too small to be seen with a standard karyotype test. CMA is the first-tier test for children with unexplained developmental delays, intellectual disability, or congenital anomalies.
Management and Therapeutic Strategies
There is no way to correct a missing piece of a chromosome, so treatment for deletion syndromes does not offer a cure. Instead, management focuses on addressing specific symptoms and supporting the individual’s development. This approach requires a coordinated effort from a multidisciplinary care team, which may include a primary care physician, geneticist, cardiologist, immunologist, and various therapists.
Early intervention is a foundation of managing these conditions. Therapies are tailored to the individual’s unique challenges and can begin in infancy. Physical therapy helps with poor muscle tone and assists in achieving motor milestones like sitting and walking. Occupational therapy focuses on developing skills for daily living, such as feeding and dressing. Speech therapy is often necessary to address delays in language development or physical challenges related to palate abnormalities.
In addition to therapies, regular monitoring for associated health issues is a standard part of care. For example, a child with 22q11.2 deletion syndrome would require regular cardiac check-ups, immune function monitoring, and blood tests to check calcium levels. Children with any deletion syndrome may also benefit from specialized educational support to address learning disabilities. The goal is to manage health problems and enhance functional abilities.