Chromosomes are thread-like structures found within the nucleus of our cells, carrying the genetic information that guides the human body’s development and function. Each human cell typically contains 46 chromosomes organized into 23 pairs: 22 autosomes and one pair of sex chromosomes, which determine biological sex. An abnormal number of chromosomes is called aneuploidy, which can involve missing or extra chromosomes. This article focuses on trisomy, a specific type of aneuploidy characterized by the presence of an extra chromosome.
The Biological Cause of an Extra Chromosome
An extra chromosome primarily results from an error during meiosis, the cell division process that produces egg and sperm cells. Meiosis ensures gametes have half the usual number of chromosomes, so that upon fertilization, the embryo has the correct total of 46. Errors in this precise separation can lead to an extra chromosome.
The most common cause of trisomy is nondisjunction, the failure of homologous chromosomes or sister chromatids to separate properly during meiosis I or meiosis II. When nondisjunction occurs, an egg or sperm cell receives an extra copy of a chromosome, while another cell receives none. If a gamete with an extra chromosome then fuses with a normal gamete during fertilization, the resulting embryo will have three copies of that particular chromosome, leading to a trisomy.
Nondisjunction is a random, spontaneous event, not generally linked to parental actions. However, advanced maternal age is a known factor that increases the likelihood of nondisjunction, particularly for certain trisomies. A less common cause of an extra chromosome is mosaicism, where the nondisjunction event occurs after fertilization in an early embryonic cell division. This results in some cells having the extra chromosome and others having the typical number, creating a mosaic pattern throughout the body.
Conditions Involving Autosomal Chromosomes
Conditions arising from an extra autosomal chromosome can significantly affect development and health. The most recognized is Down syndrome, also known as Trisomy 21. Individuals with Down syndrome often exhibit certain physical characteristics such as upward slanting eyes, a flattened facial profile, and a single deep crease across the palm of the hand.
Developmental characteristics for individuals with Down syndrome include varying degrees of intellectual disability, ranging from mild to moderate. Many individuals also experience associated health considerations, with approximately half being born with congenital heart defects. Other common health issues can include gastrointestinal abnormalities, thyroid dysfunction, and an increased risk of certain infections. The specific impact of Trisomy 21 varies widely among individuals, leading to a broad spectrum of abilities and challenges.
Edwards syndrome, or Trisomy 18, involves an extra copy of chromosome 18. This condition is much rarer than Down syndrome and is associated with more severe health challenges. Infants with Edwards syndrome often have low birth weight, a small head, and distinctive clenched hands with overlapping fingers. Life expectancy is significantly limited, with many infants not surviving beyond the first year due to complex medical complications, including severe heart defects and kidney problems.
Patau syndrome, or Trisomy 13, is even rarer than Edwards syndrome. This condition is characterized by severe health issues, including heart defects, brain or spinal cord abnormalities, and often a cleft lip or palate. Infants with Patau syndrome have a very short life expectancy, with most not surviving beyond the first few weeks or months due to profound medical complications.
Conditions Involving Sex Chromosomes
Conditions involving an extra sex chromosome often present with less severe health and developmental challenges compared to autosomal trisomies. These conditions affect sexual development and may be associated with learning or behavioral differences.
Klinefelter syndrome occurs in males who have an extra X chromosome. Individuals with Klinefelter syndrome may be taller than average and often experience hypogonadism, meaning their testes do not produce enough testosterone. This can lead to reduced muscle mass, less body hair, and infertility. Intelligence is usually within the normal range, but some individuals may experience learning difficulties, particularly with language development, and may exhibit social or behavioral differences.
Triple X syndrome, also known as Trisomy X, affects females. Many females with this condition have few or no obvious physical symptoms, and some may not even be diagnosed. When symptoms are present, they can include taller stature and potential delays in motor and language development. Most have typical intelligence, but there is an increased risk of learning difficulties, especially in speech and language, and some may experience mild behavioral or emotional challenges.
Jacobs syndrome, or XYY syndrome, affects males who have an extra Y chromosome. Males with Jacobs syndrome are often taller than average, but do not exhibit any other distinguishing physical features. Most individuals with XYY syndrome have normal fertility and development, and their intelligence is within the typical range. However, there can be an increased risk of learning disabilities, particularly speech and language delays, and some may experience behavioral challenges, such as attention deficit hyperactivity disorder (ADHD).
How Extra Chromosomes Are Identified
The identification of extra chromosomes can occur both during pregnancy and after birth through various diagnostic methods. Prenatal screening tests are often the first step, designed to assess the likelihood of a chromosomal condition without providing a definitive diagnosis. Noninvasive prenatal testing (NIPT) is a common screening method that analyzes small fragments of fetal DNA circulating in the mother’s blood, offering a high detection rate for common trisomies like Trisomy 21, 18, and 13. Ultrasound examinations during pregnancy can also identify physical markers or structural differences that may suggest the presence of an underlying chromosomal condition, prompting further investigation.
If screening tests indicate an increased risk, or if there are other medical reasons, diagnostic tests can provide a definitive answer. These procedures are invasive as they involve obtaining fetal cells directly. Chorionic villus sampling (CVS), performed between 10 and 13 weeks of pregnancy, involves taking a small sample of tissue from the placenta. Amniocentesis, performed between 15 and 20 weeks, involves drawing a small amount of amniotic fluid surrounding the fetus.
The fetal cells obtained from CVS or amniocentesis are then used to create a karyotype, which is a visual arrangement of an individual’s chromosomes. Technicians photograph the chromosomes, cut them out, and arrange them by size and banding pattern to identify any extra chromosomes or structural abnormalities. While these diagnostic tests carry a small risk of complications, such as miscarriage, they offer a precise confirmation of a trisomy. Diagnosis of an extra chromosome can also be made after birth through a simple blood test, where cells are collected and analyzed to create a karyotype.