Human cells contain 23 pairs of chromosomes, which hold the genetic instructions that guide development. These structures are composed of DNA and are inherited from each parent. Chromosome 18 is one of these pairs and is classified as an autosomal, or non-sex, chromosome, spanning approximately 78 million DNA base pairs and containing 200 to 300 genes. Because it carries this genetic material, any changes to its structure or number of copies can impact an individual’s health. The relatively low gene density of chromosome 18 may be why some numerical abnormalities are survivable past birth.
Trisomy 18 (Edwards Syndrome)
A trisomy is a genetic condition with an extra, third copy of a chromosome. Trisomy 18, or Edwards syndrome, occurs when an individual has three copies of chromosome 18, disrupting normal development and leading to a recognizable pattern of health issues. It occurs in approximately 1 in 5,000 live births.
Infants with Edwards syndrome often have a low birth weight, a small head (microcephaly), and a small jaw. Common physical characteristics include clenched fists with overlapping fingers, low-set ears, and foot abnormalities called “rocker-bottom feet.” Internally, heart and kidney defects are very common, and breathing difficulties can also occur.
There are different forms of Trisomy 18. Full trisomy, where the extra chromosome is in every cell, is the most common and severe type. In mosaic trisomy 18, the extra chromosome is only in some cells, which can lead to a milder presentation. Partial trisomy 18 occurs when only a segment of the chromosome is present in three copies, which may also result in less severe effects.
Due to numerous serious health problems, the prognosis for infants with Trisomy 18 is poor, with many pregnancies ending in stillbirth. A significant number of infants who are born do not survive beyond the first week of life. Medical care is focused on palliative measures to address symptoms related to feeding, breathing, and heart function to provide comfort.
Chromosome 18 Deletion Syndromes
Genetic conditions can also arise from the loss of chromosomal material, known as a deletion. Chromosomes are organized into a short arm, designated “p,” and a long arm, designated “q.” Deletions on either arm of chromosome 18 can lead to distinct syndromes with their own sets of characteristics.
One such condition is 18p- syndrome, where all or part of the short arm of chromosome 18 is missing. This occurs in about 1 in 50,000 births and causes various medical and developmental concerns. Individuals with 18p- syndrome may have a round face, droopy eyelids, and large ears. Developmental delays are common, with intellectual disability often in the mild to moderate range. Some may experience growth hormone deficiency or a brain malformation known as holoprosencephaly.
Another deletion disorder is 18q- syndrome, which involves a missing piece from the long arm of the chromosome. This condition often leads to developmental delays, short stature, and weak muscle tone (hypotonia). A notable feature of 18q- syndrome is its impact on the nervous system. The deletion can affect the production of myelin, a substance that insulates nerve cells for rapid communication, which contributes to some of the neurological issues seen in the condition.
Other Structural Variations
Beyond the addition or deletion of an entire chromosome arm, other structural changes to chromosome 18 can occur. These variations involve different rearrangements of the chromosome’s genetic material, resulting in unique syndromes. The specific health effects depend on which genes are involved and the nature of the structural change.
One such variation is Ring Chromosome 18, which forms when both ends of the chromosome break off and the remaining ends fuse together. The genetic material lost from the tips of the p and q arms causes the associated health issues. Because the amount of lost material differs between individuals, the effects are highly variable. Common features include an unusually small head, developmental delays, and distinct facial characteristics.
Another rare condition is Tetrasomy 18p, caused by an abnormal extra chromosome called an isochromosome. An isochromosome has two identical arms, and in this case, it is composed of two short (p) arms of chromosome 18. An individual with Tetrasomy 18p has the standard two copies of chromosome 18 plus this isochromosome, resulting in four copies of the short arm. This excess genetic material disrupts development, leading to developmental delays, changes in muscle tone, and cognitive impairment.
Genetic Counseling and Testing
Identifying chromosome 18 abnormalities often begins during pregnancy with prenatal screenings. A common screening is non-invasive prenatal testing (NIPT), a blood test analyzing fetal DNA in the mother’s bloodstream. NIPT assesses the likelihood of conditions like Trisomy 18 by measuring the amount of DNA from each chromosome. While highly accurate as a screening tool, NIPT is not a definitive diagnostic test.
If a screening test indicates a high chance of a chromosomal abnormality, diagnostic tests may be offered. A karyotype is a laboratory technique that produces an image of a person’s chromosomes, allowing for the detection of large-scale changes like an extra chromosome. This method is a standard for diagnosing conditions such as full Trisomy 18.
For a more detailed examination, a chromosomal microarray analysis (CMA) can be used. CMA is a high-resolution method that detects very small missing (deletions) or extra (duplications) pieces of chromosome material not visible on a standard karyotype. This makes it useful for identifying conditions like 18p- and 18q- syndromes with greater precision.
Genetic counseling helps families understand these tests and their results. A genetic counselor is a healthcare professional trained to explain complex genetic information, including testing options, results, and the prognosis and management of specific conditions. This support helps families make informed decisions that align with their values.