What are chromosomal abnormalities? 12 dangerous syndromes

What are chromosomal abnormalities?

Chromosomal abnormalities refer to disruptions in the number or structure of chromosomes, leading to genetic changes that can impact development, health and overall body function.

Numerical chromosomal abnormalities – Aneuploidy

This type of abnormality occurs when the fetus has an incorrect number of chromosomes, deviating from the normal human set of 46 chromosomes (arranged in 23 pairs, with one chromosome inherited from each parent per pair). This condition is also known as aneuploidy.

Aneuploidy occurs due to errors in cell division before fertilization of sperm and egg cells. Aneuploidy often arises when chromosomes fail to separate correctly during the formation of egg or sperm cells, leading to either extra or missing chromosomes. Normally, when an egg and sperm combine, they form a fertilized egg with 46 chromosomes. Aneuploidy in the resulting embryo can occur if fertilization involves an egg and sperm with chromosomal abnormalities.

The term “Trisomy” refers to the presence of three copies of a particular chromosome, while “Monosomy” refers to the presence of only one copy, instead of the typical two copies.

Common numerical chromosomal abnormalities involve either the loss or gain of a chromosome. This imbalance can lead to genetic conditions such as Down syndrome, Edwards syndrome and Patau syndrome, which result from an extra chromosome. Conversely, Turner syndrome occurs when a female is missing one sex chromosome.

Structural chromosomal abnormalities – Delections & Duplications

Structural chromosomal abnormalities occur when a portion of a chromosome is lost, duplicated, inverted or rearranged. Among these, deletions (missing chromosome segments) and duplications (extra chromosome segments) are the most common and can be detected by NIPT.

Chromosomal deletions can lead to conditions such as Cri-du-chat Syndrome (5p deletion). Chromosomal duplications can result in disorders such as 16p12.2-p11.2 Duplication Syndrome.

Risk Factors for Numerical Chromosomal Abnormalities

Most cases of chromosomal aneuploidy occur spontaneously, without a specific known cause. However, research has identified several risk factors that may increase the likelihood of numerical chromosomal abnormalities, including:

• Parental age: The risk increases with the mother’s age, particularly after the age of 35. This is because eggs in older women are more likely to undergo abnormal division. The father’s age can also be a contributing factor, although its impact is less pronounced compared to the mother’s age.
• Genetic factors: Some individuals may have genetic factors that increase the likelihood of having a baby with a chromosomal aneuploidy. If there is a history of chromosomal aneuploidy in the family, the risk of the condition in future generations will be higher.
• Environmental factors: Exposure to harmful substances such as pesticides, radiation, benzene, lead, and certain medications can increase risk.
• Underlying maternal health conditions: Certain health conditions, such as diabetes, thyroid disorders, and obesity, can increase the risk.
• Unhealthy lifestyle: Smoking, alcohol consumption, and drug use can increase the risk.

Sequelae of Aneuploidy

Most cases of numerical chromosomal abnormalities result in high neonatal mortality rates. In cases where the fetus survives, aneuploidy can cause various congenital disorders and long-term complications, including:

• Delayed cognitive and motor development, leading to intellectual disabilities and learning difficulties.
• Physical abnormalities, including distinct facial features and limb deformities.
• Cardiac complications, organ dysfunction, issues affecting the kidneys or reproductive system.
• Reduced life expectancy, particularly when the condition severely impacts organ function or the nervous system.
• Behavioral and psychological challenges, increasing the risk of anxiety, depression and social difficulties.
• Reproductive issues, such as infertility or underdeveloped reproductive organs.

Common Syndromes and Conditions Associated with Chromosomal Abnormalities

1. Down Syndrome (Trisomy 21)

This is the most common trisomy disorder in live births, caused by the presence of three copies of chromosome 21. The incidence rate is 1 in 660 live births.

Although individuals with Down syndrome can survive into adulthood, their clinical features vary. Common characteristics include:

• Mild to moderate intellectual disability and developmental delays.
• Distinct craniofacial features, such as a flat facial profile, upward-slanting eyes, a small nose, and a protruding tongue.
• Congenital heart defects.
• Hypotonia.

2. Edwards Syndrome (Trisomy 18)

This is the second most common trisomy disorder in live births, caused by an extra copy of chromosome 18. The survival rate is very low, with most infants not living beyond their first year. The incidence rate is 1 in 3,333 live births.

Common features include:

• Intrauterine growth restriction and severe developmental delays.
• Profound intellectual disability.
• Limb abnormalities.
• Congenital heart defects and multi-organ complications (e.g., cardiovascular and gastrointestinal abnormalities).

3. Patau Syndrome (Trisomy 13)

This is a severe genetic disorder caused by the presence of three copies of chromosome 13, with an incidence rate of 1 in 5,000 live births, meaning that 1 in 5,000 surviving newborns is affected by Patau syndrome. Most infants with this condition have a very short lifespan, typically not surviving beyond the first year. However, the majority of prenatally diagnosed cases result in miscarriage or stillbirth.

Common clinical features include:

• Severe abnormalities in major organs, including the heart, brain, kidneys.
• Profound developmental and intellectual disability.
• Facial abnormalities, such as cleft lip, cleft palate, microphthalmia, polydactyly.

4. Turner Syndrome (XO)

This syndrome only affects females and occurs when they have only one X chromosome (45,X) instead of the usual XX pair. The incidence is 1 in 2,000 live female births, with a high miscarriage rate in monosomy X pregnancies.

Common clinical features:

• Short stature.
• Congenital heart defects.
• Ovarian dysfunction, leading to amenorrhea and infertility.

5. Jacobs Syndrome (XYY)

The syndrome affects males and occurs when they have an extra Y chromosome (47,XYY). The incidence is 1 in 1,000 live male births.

Children born with this syndrome typically have normal fertility but may exhibit the following characteristics:

• Increased risk of attention deficit hyperactivity disorder and autism spectrum disorders.
• Learning difficulties and speech delays.
• Delayed language development.

6. Klinefelter Syndrome (XXY)

The syndrome only affects males and occurs when they have an extra X chromosome (47,XXY) instead of the typical XY. The incidence is 1 in 500 live male births.

Clinical manifestations may vary, but the common characteristics of the syndrome include:

• Learning difficulties, speech delays, and language development issues.
• Taller-than-average height.
• Undeveloped testes, often leading to infertility.

7. Triple X Syndrome (XXX)

The syndrome affects females, occurring when they have three X chromosomes instead of the usual two (47,XXX). The incidence is 1 in 1,000 live female births. Most women with this condition have normal physical appearance and fertility with no significant external abnormalities.

Common characteristics:

• Taller-than-average height.
• Learning difficulties, speech delays, and language development issues.
• Behavioral and emotional challenges.
• Delayed motor skills development.
• Irregular sexual development and possible premature ovarian failure.

8. Severe variants of Klinefelter Syndrome

These syndrome variants occur when males inherit more than two X chromosomes (e.g., XXXY or XXXXY). These conditions are rarer and more severe than the typical 47,XXY form.

These variants cause severe developmental disorders, leading to significant difficulties in communication and motor skills. Affected males often experience severe testosterone deficiency, resulting in serious reproductive dysfunction, potentially leading to complete infertility. Additionally, they may present with skeletal abnormalities, such as abnormally long limbs and coarse facial features.

9. DiGeorge Syndrome

DiGeorge syndrome is the most common structural chromosomal abnormality, occurring when a small segment is deleted from chromosome 22 (22q11.2). The incidence of the syndrome is approximately 1 in every 3,000 to 6,000 births, with a prevalence of 1 in 185 pregnancies at high risk for this syndrome.

The characteristics of children born with this condition typically include:

• Facial deformities such as cleft palate and hypoplasia of the soft palate.
• Congenital heart defects.
• Immunodeficiency.
• Intellectual developmental delay.
• Learning and language difficulties.
• Increased risk of autism spectrum disorder and mental health disorders.

10. Trisomy 9

Abnormality occurs when there is an extra copy of chromosome 9. Affected infants often exhibit microcephaly, a prominent forehead, widely spaced eyes, low-set ears, abnormally long fingers, and limb deformities. Severe congenital heart defects, such as ventricular septal defects and abnormal heart valves, are common. The prognosis is poor, and most infants do not survive beyond their first year of life.

11. Trisomy 16

Abnormality results from an extra copy of chromosome 16. Complete trisomy 16 is typically incompatible with life and usually leads to early miscarriage. However, in cases of mosaic trisomy 16, affected infants may survive but often have low birth weight due to intrauterine growth restriction, or experience serious congenital heart defects (such as pulmonary artery stenosis, heart valve abnormalities), skeletal abnormalities (including scoliosis, congenital hip dislocation), intellectual disabilities, and mild to moderate motor impairments.

12. Trisomy 22

Abnormality occurs when an extra copy of chromosome 22 is present. Complete trisomy 22 usually results in early miscarriage, while some cases of mosaic trisomy 22 allow for survival. Affected infants may present with congenital defects (such as ventricular septal defects, aortic abnormalities), mild craniofacial differences (including small ears, slanted eyes), immune system deficiencies, more prone to infections, intellectual disabilities, neurological disorders, and seizures.

Conclusion

This article has explained what chromosomal abnormalities are and presented 12 critical syndromes in fetuses that may result from such abnormalities. Chromosomal anomalies can cause significant congenital defects and long-term consequences. Therefore, early screening is essential for timely detection, appropriate clinical management and informed decision-making regarding pregnancy.