Chromosomal Abnormalities

What chromosomes are

Chromosomes are long strands of DNA wrapped around proteins. Humans normally have 46: 22 pairs of autosomes plus 2 sex chromosomes (XX in females, XY in males). One of each pair comes from each parent. Each chromosome carries hundreds to thousands of genes, so gaining or losing even a small piece changes the dose of many genes at once.

Types of chromosomal abnormalities

Numerical abnormalities (aneuploidy)

An extra or missing whole chromosome, usually from nondisjunction, when chromosomes fail to separate during egg or sperm formation.

Structural abnormalities

• Deletions: a missing piece, such as 22q11.2 deletion syndrome, cri-du-chat syndrome (5p deletion) and Williams syndrome (7q11.23).
• Duplications: an extra copy of a segment.
• Translocations: pieces swapped between chromosomes. A balanced translocation, with no DNA lost, usually causes no health problems for the carrier but raises the risk of miscarriage and of unbalanced chromosomes in children. Robertsonian translocations can cause inherited Down syndrome.
• Inversions: a segment flipped in orientation.
• Ring chromosomes and isochromosomes.

Mosaicism

Some cells have the abnormality and others do not, because the error happened after fertilization. Features are often milder.

Uniparental disomy and imprinting

Inheriting both copies of a chromosome from one parent can cause conditions such as some cases of Prader-Willi syndrome and Angelman syndrome.

Causes and risk factors

• Random errors: most chromosomal abnormalities are not inherited and happen by chance.
• Maternal age: the risk of trisomies rises with the mother's age, especially from age 35. The chance of a baby with Down syndrome is about 1 in 1,250 at age 25, about 1 in 350 at 35 and about 1 in 30 at 45.
• Parental balanced translocation: increases risk in each pregnancy.
• Previous pregnancy with a chromosomal condition.

Chromosomal abnormalities cause about half of first-trimester miscarriages.

Signs after birth

Features depend on the condition but can include:

• low muscle tone, feeding difficulties
• distinctive facial features
• heart defects, cleft lip or palate, kidney or other organ differences
• growth problems or short stature
• developmental delay and intellectual disability
• delayed or absent puberty and infertility (sex chromosome conditions)

Testing

Prenatal screening

Screening estimates the chance of a chromosomal condition; it does not diagnose it.

• Cell-free DNA screening (NIPT): a blood test from about 10 weeks that analyzes fragments of placental DNA; highly sensitive for trisomy 21 and good for trisomies 18 and 13 and sex chromosome conditions.
• First-trimester combined screening: ultrasound measurement of the nuchal translucency plus blood tests at 11 to 14 weeks.
• Second-trimester quad screen.
• Anatomy ultrasound at 18 to 22 weeks.

ACOG recommends that all pregnant people be offered both screening and diagnostic testing options, regardless of age.

Prenatal diagnosis

• Chorionic villus sampling (CVS): at 10 to 13 weeks, sampling the placenta.
• Amniocentesis: from about 15 weeks, sampling the amniotic fluid.

Both carry a small risk of miscarriage and give a definite answer.

Testing after birth

• Karyotype: a picture of all chromosomes, used to confirm conditions like Down syndrome or Turner syndrome and balanced translocations.
• Chromosomal microarray: detects small deletions and duplications not visible on a karyotype; first-line for unexplained developmental delay or multiple birth differences.
• FISH: targets a specific region, such as 22q11.2.
• Genome sequencing in selected cases.

Treatment and support

Chromosomal abnormalities cannot be reversed, but many of their effects can be treated:

• heart surgery for congenital heart defects
• early intervention: physiotherapy, speech and occupational therapy
• special education support
• hormone treatments for growth and puberty (Turner and Klinefelter syndromes)
• regular screening for associated problems, such as thyroid disease and hearing loss in Down syndrome
• genetic counseling for families, including recurrence risk and options in future pregnancies

Frequently asked questions

What are the most common chromosomal abnormalities?

The most common in live births are Down syndrome (trisomy 21), Klinefelter syndrome (XXY), triple X, XYY syndrome and Turner syndrome. Trisomies 18 and 13 are less common and more severe. Small deletions such as 22q11.2 deletion syndrome are also relatively common.

What causes chromosomal abnormalities?

Most are caused by random errors when eggs or sperm form, so chromosomes do not separate properly. The risk of some, especially trisomies, rises with the mother's age. Less often, a parent carries a balanced rearrangement that can be passed on in unbalanced form.

Can chromosomal abnormalities be detected during pregnancy?

Yes. Screening tests such as cell-free DNA and first-trimester combined screening estimate the chance. Diagnostic tests, chorionic villus sampling and amniocentesis, give a definite answer by examining the baby's chromosomes directly.

Are chromosomal abnormalities inherited?

Most are not. They usually happen by chance. However, a parent with a balanced translocation can pass on an unbalanced form, and some conditions can recur. Genetic counseling helps families understand their risk in future pregnancies.

Can a chromosomal abnormality be fixed?

No. The chromosome change is present in the body's cells and cannot be reversed. But many health problems linked to chromosomal conditions can be treated, and early support helps children reach their full potential.