Chromosomal abnormalities cause various disorders. Abnormalities that affect autosomes (the 22 paired chromosomes that are alike in males and females) are more common than those that affect sex chromosomes (X and Y).
Chromosomal abnormalities fit into several categories but broadly may be considered as numerical or structural. Numerical abnormalities may involve a part of, or the entire, chromosome.
Numerical abnormalities include
Trisomy (an extra chromosome)
Monosomy (a missing chromosome)
Structural abnormalities include
Translocations (abnormalities in which a whole chromosome or segments of chromosomes inappropriately join with other chromosomes)
Deletions and duplications of various parts of chromosomes
Some specific terms from the field of genetics are important for describing chromosomal abnormalities:
Aneuploidy: The most common chromosomal abnormality caused by an extra or missing chromosome.
Karyotype: The full set of chromosomes in a person's cells.
Genotype: The genetic constitution determined by the karyotype.
Phenotype: The person's clinical findings including outward appearance—the biochemical, physiologic, and physical makeup as determined by the genotype and environmental factors (see General Principles of Medical Genetics Overview of Genetics A gene, the basic unit of heredity, is a segment of DNA containing all the information necessary to synthesize a polypeptide (protein) or a functional RNA molecule. Protein synthesis, folding... read more ).
Mosaicism Mosaicism Certain situations represent aberrant inheritance, often because genes or chromosomes are altered. However, some of these alterations, such as mosaicism, are very common; others, such as polymorphisms... read more : The presence of ≥ 2 cell lines differing in genotype in a person who has developed from a single fertilized egg.
Diagnosis of Chromosomal Abnormalities
Chromosomal analysis (karyotyping)
Fluorescent in situ hybridization (FISH)
Chromosomal microarray analysis (array comparative genomic hybridization)
(See also Next-generation sequencing technologies Genetic Diagnostic Technologies Genetic diagnostic technology is rapidly improving. A small amount of DNA can be amplified using the polymerase chain reaction (PCR) process, which can produce millions of copies of a gene or... read more .)
Lymphocytes are typically used for chromosomal analysis, except prenatally, when amniocytes or cells from placental chorionic villi are used (see Amniocentesis Amniocentesis Prenatal procedures that provide a definitive diagnosis of genetic disorders are invasive and involve some fetal risk. Women may choose to have prenatal procedures to know of fetal abnormalities... read more and Chorionic Villus Sampling Chorionic Villus Sampling Prenatal procedures that provide a definitive diagnosis of genetic disorders are invasive and involve some fetal risk. Women may choose to have prenatal procedures to know of fetal abnormalities... read more ). A karyotype analysis involves blocking cells in mitosis during metaphase and staining the condensed chromosomes. Chromosomes from single cells are photographed, and their images are arranged, forming a karyotype.
Several techniques are used to better delineate the chromosomes:
In classical banding (eg, G [Giemsa]-banding, Q [fluorescent]-banding, and C-banding), a dye is used to stain bands on the chromosomes.
High-resolution chromosome analysis uses special culture methods to obtain a high percentage of prophase and prometaphase spreads. The chromosomes are less condensed than in routine metaphase analysis, and the number of identifiable bands is expanded, allowing a more sensitive karyotype analysis.
Spectral karyotyping analysis (also called chromosome painting) uses chromosome-specific multicolor fluorescent in situ hybridization (FISH) techniques that improve the visibility of certain defects, including translocations and inversions.
Chromosomal microarray analysis (CMA), also called array comparative genomic hybridization (aCGH), is a single-step technique that allows the entire genome to be scanned for chromosome dosage abnormalities, including increases (duplications) or decreases (deletions), which may also be suggestive of an unbalanced translocation. Single nucleotide polymorphism (SNP) microarray analysis has the additional ability to detect regions of homozygosity, which may be seen in cases where parents share common ancestry (consanguinity), and also when there is uniparental disomy Uniparental disomy Certain situations represent aberrant inheritance, often because genes or chromosomes are altered. However, some of these alterations, such as mosaicism, are very common; others, such as polymorphisms... read more (ie, both copies of a chromosome, or part of a chromosome, are inherited from one parent, instead of 1 copy from the mother and 1 copy from the father). It is important to note that CMA does not detect balanced rearrangements (eg, translocations, inversions), which are not associated with deletions or duplications.
Noninvasive prenatal screening (NIPS) methods are used for prenatal genetic screening tests Noninvasive Prenatal Fetal Screening Tests Noninvasive prenatal screening for genetic disorders, unlike invasive testing, has no risk of test-related complications. Noninvasive maternal screening can help women decide whether to have... read more (1 Screening reference Chromosomal abnormalities cause various disorders. Abnormalities that affect autosomes (the 22 paired chromosomes that are alike in males and females) are more common than those that affect... read more ). These methods involve obtaining cell-free fetal DNA sequences from a maternal blood sample, primarily for trisomy 21 (Down syndrome Down Syndrome (Trisomy 21) Down syndrome is an abnormality of chromosome 21 that can cause intellectual disability, microcephaly, short stature, and characteristic facies. Diagnosis is suggested by physical anomalies... read more ), trisomy 13 Trisomy 13 Trisomy 13 is caused by an extra chromosome 13 and causes abnormal forebrain, midface, and eye development; severe intellectual disability; heart defects; and small birth size. Diagnosis is... read more , trisomy 18 Trisomy 18 Trisomy 18 is caused by an extra chromosome 18 and is usually associated with intellectual disability, small birth size, and various congenital anomalies, including severe microcephaly, heart... read more , and sex chromosome aneuploidy. NIPS has been used as a screening test for common microdeletion syndromes Microdeletion and Microduplication Syndromes Microdeletion and microduplication syndromes are disorders caused by submicroscopic deletions or duplications of contiguous genes on particular parts of chromosomes. Postnatal diagnosis is suspected... read more (eg, 22q11 deletion). It is important to note that the sensitivity and specificity vary for different chromosomal abnormalities. It is recommended that any abnormality detected with NIPS should be confirmed with a diagnostic test.
1. American College of Obstetricians and Gynecologists’ Committee on Practice Bulletins—Obstetrics; Committee on Genetics; Society for Maternal-Fetal Medicine: Screening for fetal chromosomal abnormalities: ACOG Practice Bulletin, Number 226. Obstet Gynecol 136(4):e48-e69, 2020. doi: 10.1097/AOG.0000000000004084